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22 pages, 6680 KiB

Open AccessArticle

The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study

by Lianxiang Luo, Qu Wang and Yinglin Liao

Mar. Drugs 2022, 20(5), 319; https://doi.org/10.3390/md20050319 - 12 May 2022

Cited by 8 | Viewed by 3220

Abstract

Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen [...] Read more.

Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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15 pages, 7594 KiB

Open AccessEditor’s ChoiceArticle

Discovery of New Secondary Metabolites from Marine Bacteria Hahella Based on an Omics Strategy

by Shufen He, Peishan Li, Jingxuan Wang, Yanzhu Zhang, Hongmei Lu, Liufei Shi, Tao Huang, Weiyan Zhang, Lijian Ding, Shan He and Liwei Liu

Mar. Drugs 2022, 20(4), 269; https://doi.org/10.3390/md20040269 - 18 Apr 2022

Cited by 5 | Viewed by 4170

Abstract

Hahella is one characteristic genus under the Hahellaceae family and shows a good potential for synthesizing new natural products. In this study, we examined the distribution of the secondary metabolite biosynthetic gene cluster (SMBGC) under Hahella with anti-SMASH. The results derived from five [...] Read more.

Hahella is one characteristic genus under the Hahellaceae family and shows a good potential for synthesizing new natural products. In this study, we examined the distribution of the secondary metabolite biosynthetic gene cluster (SMBGC) under Hahella with anti-SMASH. The results derived from five genomes released 70 SMBGCs. On average, each strain contains 12 gene clusters, and the most abundant ones (45.7%) are from the family of non-ribosomal peptide synthetase (NRPS) and non-ribosomal peptide synthetase hybrid with polyketide synthase (NRPS/PKS), indicating a great potential to find bioactive compounds. The comparison of SMBGC between H. chejuensis and other species showed that H. chejuensis contained two times more gene clusters than H. ganghwensis. One strain, designed as NBU794, was isolated from the mangrove soil of Dongzhai Port in Haikou (China) by iChip. The 16S rRNA gene of NBU794 exhibited 99% identity to H. chejuensis KCTC 2396 and clustered with the H. chejuensis clade on the phylogenetic trees. Genome mining on strain NBU794 released 17 SMBGCs and two groups of bioactive compounds, which are chejuenolide A-C and nine prodiginines derivatives. The prodiginines derivatives include the well-known lead compound prodigiosin and two new compounds, 2-methyl-3-pentyl-4-O-methyl-prodiginine and 2-methyl-3-octyl-prodiginine, which were identified through fragmentation analysis based on LC-MS/MS. The anti-microbial activity assay showed prodigiosin and 2-methyl-3-heptyl-prodiginine exhibited the best performance in inhibiting Escherichia coli, Salmonella paratyphi B, MASA Staphylococcus aureus, Bacillus subtilis, and Candida albicans. Moreover, the yield of prodigiosin in H. chejuensis NBU794 was also evaluated, which could reach 1.40 g/L under the non-optimized condition and increase to 5.83 g/L in the modified ISP4 medium with macroporous adsorption beads added, indicating that NBU794 is a promising source of prodigiosin. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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13 pages, 2828 KiB

Open AccessArticle

Phycocyanin Ameliorates Colitis-Associated Colorectal Cancer by Regulating the Gut Microbiota and the IL-17 Signaling Pathway

by Dongjin Pan, Bingyao Huang, Yuman Gan, Chenghai Gao, Yonghong Liu and Zhenzhou Tang

Mar. Drugs 2022, 20(4), 260; https://doi.org/10.3390/md20040260 - 9 Apr 2022

Cited by 23 | Viewed by 4422

Abstract

Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota [...] Read more.

Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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11 pages, 1601 KiB

Open AccessArticle

Aromatic Acids and Leucine Derivatives Produced from the Deep-Sea Actinomycetes Streptomyces chumphonensis SCSIO15079 with Antihyperlipidemic Activities

by Ziqi Su, Kunlong Li, Xiaowei Luo, Yongyan Zhu, Shao-Yu Mai, Quanhong Zhu, Bin Yang, Xuefeng Zhou and Huaming Tao

Mar. Drugs 2022, 20(4), 259; https://doi.org/10.3390/md20040259 - 7 Apr 2022

Cited by 5 | Viewed by 2778

Abstract

Six new aromatic acids (1–6) and three new leucine derivatives containing an unusual oxime moiety (7–9) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (10 [...] Read more.

Six new aromatic acids (1–6) and three new leucine derivatives containing an unusual oxime moiety (7–9) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (10–11). The structures of 1–9 including absolute configurations were determined by detailed NMR, MS, and experimental and calculated electronic circular dichroism spectroscopic analyses. Compounds 1–9 were evaluated for their antimicrobial and cytotoxicity activities, as well as their effects on intracellular lipid accumulation in HepG2 cells. Compounds 3 and 4, with the most potent inhibitory activity on intracellular lipid accumulation at 10 μM, were revealed with potential antihyperlipidemic effects, although the mechanism needs to be further studied. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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17 pages, 5450 KiB

Open AccessArticle

The Emerging Evidence for a Protective Role of Fucoidan from Laminaria japonica in Chronic Kidney Disease-Triggered Cognitive Dysfunction

by Zhihui Ma, Zhiyou Yang, Xinyue Feng, Jiahang Deng, Chuantong He, Rui Li, Yuntao Zhao, Yuewei Ge, Yongping Zhang, Cai Song and Saiyi Zhong

Mar. Drugs 2022, 20(4), 258; https://doi.org/10.3390/md20040258 - 7 Apr 2022

Cited by 14 | Viewed by 3899

Abstract

This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 [...] Read more.

This study aimed to explore the mechanism of fucoidan in chronic kidney disease (CKD)-triggered cognitive dysfunction. The adenine-induced ICR strain CKD mice model was applied, and RNA-Seq was performed for differential gene analysis between aged-CKD and normal mice. As a result, fucoidan (100 and 200 mg kg⁻¹) significantly reversed adenine-induced high expression of urea, uric acid in urine, and creatinine in serum, as well as the novel object recognition memory and spatial memory deficits. RNA sequencing analysis indicated that oxidative and inflammatory signaling were involved in adenine-induced kidney injury and cognitive dysfunction; furthermore, fucoidan inhibited oxidative stress via GSK3β-Nrf2-HO-1 signaling and ameliorated inflammatory response through regulation of microglia/macrophage polarization in the kidney and hippocampus of CKD mice. Additionally, we clarified six hallmarks in the hippocampus and four in the kidney, which were correlated with CKD-triggered cognitive dysfunction. This study provides a theoretical basis for the application of fucoidan in the treatment of CKD-triggered memory deficits. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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11 pages, 2055 KiB

Open AccessArticle

New 3-Acyl Tetramic Acid Derivatives from the Deep-Sea-Derived Fungus Lecanicillium fusisporum

by Xinya Xu, Yanhui Tan, Chenghai Gao, Kai Liu, Zhenzhou Tang, Chunju Lu, Haiyan Li, Xiaoyong Zhang and Yonghong Liu

Mar. Drugs 2022, 20(4), 255; https://doi.org/10.3390/md20040255 - 6 Apr 2022

Cited by 5 | Viewed by 2556

Abstract

Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A–G (1–7), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures [...] Read more.

Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A–G (1–7), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures were elucidated by extensive spectroscopic data analysis, quantum chemistry calculations and chemical reaction. Compounds 1, 2, 5–7 exhibited moderate anti-inflammatory activity against NF-κB production using lipopolysaccharide (LPS) induced RAW264.7 cells with EC₅₀ values range of 18.49–30.19 μM. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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13 pages, 2151 KiB

Open AccessArticle

Adsorption Characteristics and Enrichment of Emodin from Marine-Derived Aspergillus flavipes HN4-13 Extract by Macroporous Resin XAD-16

by Lizhi Gong, Yuzhen Wu, Xiaohan Qiu, Xiujuan Xin, Faliang An and Miaomiao Guo

Mar. Drugs 2022, 20(4), 231; https://doi.org/10.3390/md20040231 - 28 Mar 2022

Cited by 5 | Viewed by 2454

Abstract

Emodin, a hydroxyanthraquinone derivative, has been used as medicine for more than 2000 years due to its extensive pharmacological activities. Large-scale production of emodin has been achieved by optimizing the fermentation conditions of marine-derived Aspergillus flavus HN4-13 in a previous study. However, the [...] Read more.

Emodin, a hydroxyanthraquinone derivative, has been used as medicine for more than 2000 years due to its extensive pharmacological activities. Large-scale production of emodin has been achieved by optimizing the fermentation conditions of marine-derived Aspergillus flavus HN4-13 in a previous study. However, the fermentation broth contained complex unknown components, which adversely affected the study of emodin. Herein, the conditions for the enrichment of emodin from A. flavipes HN4-13 extract using XAD-16 resin were optimized, and a separation method with high efficiency, simple operation, a low cost, and a large preparative scale was established. The adsorption process of emodin on the XAD-16 resin conformed to pseudo-second-order kinetics and Langmuir models. The optimal conditions for the adsorption process were as follows: An emodin concentration, flow rate, and loading volume of 0.112 mg/mL, 2 BV/h, and 10 BV, respectively. For desorption, 50% ethanol was used to elute impurities and 80% ethanol was used to desorb emodin. After enrichment with XAD-16 resin, the emodin content increased from 1.16% to 11.48%, and the recovery rate was 75.53% after one-step treatment. These results demonstrate the efficiency of the simple adsorption–desorption strategy, using the XAD-16 resin for emodin enrichment. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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14 pages, 39370 KiB

Open AccessArticle

Fucoxanthin Attenuates Free Fatty Acid-Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism/Oxidative Stress/Inflammation via the AMPK/Nrf2/TLR4 Signaling Pathway

by Jiena Ye, Jiawen Zheng, Xiaoxiao Tian, Baogui Xu, Falei Yuan, Bin Wang, Zuisu Yang and Fangfang Huang

Mar. Drugs 2022, 20(4), 225; https://doi.org/10.3390/md20040225 - 25 Mar 2022

Cited by 23 | Viewed by 4379

Abstract

Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) [...] Read more.

Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) cell model in this study. The results showed that the content of superoxide dismutase in the FFA group was 9.8 ± 1.0 U/mgprot, while that in the fucoxanthin high-dose (H-Fx) group (2 μg/mL) increased to 22.9 ± 0.6 U/mgprot. The content of interleukin-1β in the FFA group was 89.3 ± 3.6 ng/mL, while that in the H-Fx group was reduced to 53.8 ± 2.8 ng/mL. The above results indicate that fucoxanthin could alleviate the FFA-induced oxidative stress and inflammatory levels in the liver cells. Oil red-O staining revealed visible protrusions and a significant decrease in the number of lipid droplets in the cytoplasm of cells in the fucoxanthin group. These findings on the mechanisms of action suggest that fucoxanthin can repair FFA-induced NAFLD via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and nuclear factor erythroid-2-related factor 2-mediated (Nrf2) signaling pathway, as well as by downregulating the expression of the Toll-like receptor 4-mediated (TLR4) signaling pathway. Fucoxanthin exhibited alleviating effects in the FFA-induced NAFLD model and could be explored as a potential anti-NAFLD substance. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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11 pages, 2199 KiB

Open AccessArticle

Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404

by Qingyun Peng, Weihao Chen, Xiuping Lin, Jiao Xiao, Yonghong Liu and Xuefeng Zhou

Mar. Drugs 2022, 20(3), 212; https://doi.org/10.3390/md20030212 - 17 Mar 2022

Cited by 17 | Viewed by 3098

Abstract

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), [...] Read more.

Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC₅₀ = 25 μg/mL) and Klebsiella pneumoniae (IC₅₀ = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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15 pages, 3819 KiB

Open AccessArticle

Pyranodipyran Derivatives with Tyrosyl DNA Phosphodiesterase 1 Inhibitory Activities and Fluorescent Properties from Aspergillus sp. EGF 15-0-3

by Xia Wei, Fang-Ting Wang, Mei-Xia Si-Tu, Hao Fan, Jin-Shan Hu, Hao Yang, Shan-Yue Guan, Lin-Kun An and Cui-Xian Zhang

Mar. Drugs 2022, 20(3), 211; https://doi.org/10.3390/md20030211 - 17 Mar 2022

Cited by 10 | Viewed by 2507

Abstract

Four new benzodipyran racemates, namely (±)-aspergiletals A–D (3–6), representing a rare pyrano[4,3-h]chromene scaffold were isolated together with eurotiumide G (1) and eurotiumide F (2) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All [...] Read more.

Four new benzodipyran racemates, namely (±)-aspergiletals A–D (3–6), representing a rare pyrano[4,3-h]chromene scaffold were isolated together with eurotiumide G (1) and eurotiumide F (2) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All the corresponding optically pure enantiomers were successfully separated by a chiral HPLC column. The structures and configurations of all the compounds were elucidated based on the combination of NMR and HRESIMS data, chiral separation, single-crystal X-ray diffraction, quantum chemical ¹³C NMR, and electronic circular dichroism calculations. Meanwhile, the structure of eurotiumide G was also revised. The TDP1 inhibitor activities and photophysical properties of the obtained compounds were evaluated. In the TDP1 inhibition assay, as a result of synergy between (+)-6 and (−)-6, (±)-6 displayed strong inhibitory activity to TDP1 with IC₅₀ values of 6.50 ± 0.73 μM. All compounds had a large Stokes shift and could be utilized for elucidating the mode of bioactivities by fluorescence imaging. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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11 pages, 3997 KiB

Open AccessArticle

Anti-Osteoclastogenic and Antibacterial Effects of Chlorinated Polyketides from the Beibu Gulf Coral-Derived Fungus Aspergillus unguis GXIMD 02505

by Yanting Zhang, Zhichao Li, Bingyao Huang, Kai Liu, Shuai Peng, Xinming Liu, Chenghai Gao, Yonghong Liu, Yanhui Tan and Xiaowei Luo

Mar. Drugs 2022, 20(3), 178; https://doi.org/10.3390/md20030178 - 28 Feb 2022

Cited by 22 | Viewed by 3250

Abstract

One new depsidone derivative, aspergillusidone H (3), along with seven known biosynthetically related chlorinated polyketides, were obtained from the Beibu Gulf coral-derived fungus Aspergillus unguis GXIMD 02505. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. Notably, the X-ray [...] Read more.

One new depsidone derivative, aspergillusidone H (3), along with seven known biosynthetically related chlorinated polyketides, were obtained from the Beibu Gulf coral-derived fungus Aspergillus unguis GXIMD 02505. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. Notably, the X-ray crystal structure of 2 and the previously unknown absolute configuration of 8, assigned by ECD calculations, are described here for the first time. Compounds 1–5, 7 and 8 exhibited inhibition of lipopolysaccharide (LPS)-induced NF-κB in RAW 264.7 macrophages at 20 μM. In addition, the two potent inhibitors (2 and 7) dose-dependently suppressed RANKL-induced osteoclast differentiation without any evidence of cytotoxicity in bone marrow macrophages cells (BMMs). This is the first report of osteoclastogenesis inhibitory activity for the metabolites of these kinds. Besides, compounds 1, 2, 4, and 6–8 showed inhibitory activity against marine biofilm-forming bacteria, methicillin-resistant Staphylococcus aureus, Microbulbifer variabilis, Marinobacterium jannaschii, and Vibrio pelagius, with their MIC values ranging from 2 to 64 μg/mL. These findings provide a basis for further development of chlorinated polyketides as potential inhibitors of osteoclast differentiation and/or for use as anti-fouling agents. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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11 pages, 2093 KiB

Open AccessArticle

Sesquiterpene and Sorbicillinoid Glycosides from the Endophytic Fungus Trichoderma longibrachiatum EN-586 Derived from the Marine Red Alga Laurencia obtusa

by Ying Wang, Xiao-Ming Li, Sui-Qun Yang, Fan-Zhong Zhang, Bin-Gui Wang, Hong-Lei Li and Ling-Hong Meng

Mar. Drugs 2022, 20(3), 177; https://doi.org/10.3390/md20030177 - 28 Feb 2022

Cited by 12 | Viewed by 2730

Abstract

An unusual sesquiterpene glycoside trichoacorside A (1) and two novel sorbicillinoid glycosides sorbicillisides A (2) and B (3), together with a known compound sorbicillin (4), were isolated and identified from the culture extract of an [...] Read more.

An unusual sesquiterpene glycoside trichoacorside A (1) and two novel sorbicillinoid glycosides sorbicillisides A (2) and B (3), together with a known compound sorbicillin (4), were isolated and identified from the culture extract of an endophytic fungus Trichoderma longibrachiatum EN-586, obtained from the marine red alga Laurencia obtusa. Trichoacorside A (1) is the first representative of a glucosamine-coupled acorane-type sesquiterpenoid. Their structures were elucidated based on detailed interpretation of NMR and mass spectroscopic data. The absolute configurations were determined by X-ray crystallographic analysis, chemical derivatization, and DP4+ probability analysis. The antimicrobial activities of compounds 1–4 against several human, aquatic, and plant pathogens were evaluated. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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21 pages, 5067 KiB

Open AccessArticle

Preparation, Identification, Molecular Docking Study and Protective Function on HUVECs of Novel ACE Inhibitory Peptides from Protein Hydrolysate of Skipjack Tuna Muscle

by Shuo-Lei Zheng, Qian-Bin Luo, Shi-Kun Suo, Yu-Qin Zhao, Chang-Feng Chi and Bin Wang

Mar. Drugs 2022, 20(3), 176; https://doi.org/10.3390/md20030176 - 27 Feb 2022

Cited by 46 | Viewed by 4330

Abstract

To prepare bioactive peptides with high angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) activity, Alcalase was selected from five kinds of protease for hydrolyzing Skipjack tuna (Katsuwonus pelamis) muscle, and its best hydrolysis conditions were optimized using single factor and response surface experiments. Then, [...] Read more.

To prepare bioactive peptides with high angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) activity, Alcalase was selected from five kinds of protease for hydrolyzing Skipjack tuna (Katsuwonus pelamis) muscle, and its best hydrolysis conditions were optimized using single factor and response surface experiments. Then, the high ACEi protein hydrolysate (TMPH) of skipjack tuna muscle was prepared using Alcalase under the optimum conditions of enzyme dose 2.3%, enzymolysis temperature 56.2 °C, and pH 9.4, and its ACEi activity reached 72.71% at 1.0 mg/mL. Subsequently, six novel ACEi peptides were prepared from TMPH using ultrafiltration and chromatography methods and were identified as Ser-Pro (SP), Val-Asp-Arg-Tyr-Phe (VDRYF), Val-His-Gly-Val-Val (VHGVV), Tyr-Glu (YE), Phe-Glu-Met (FEM), and Phe-Trp-Arg-Val (FWRV), with molecular weights of 202.3, 698.9, 509.7, 310.4, 425.6, and 606.8 Da, respectively. SP and VDRYF displayed noticeable ACEi activity, with IC₅₀ values of 0.06 ± 0.01 and 0.28 ± 0.03 mg/mL, respectively. Molecular docking analysis illustrated that the high ACEi activity of SP and VDRYF was attributed to effective interaction with the active sites/pockets of ACE by hydrogen bonding, electrostatic force, and hydrophobic interaction. Furthermore, SP and VDRYF could significantly up-regulate nitric oxide (NO) production and down-regulate endothelin-1 (ET-1) secretion in HUVECs after 24 h treatment, but also abolish the negative effect of 0.5 μM norepinephrine (NE) on the generation of NO and ET-1. Therefore, ACEi peptides derived from skipjack tuna (K. pelamis) muscle, especially SP and VDRYF, are beneficial components for functional food against hypertension and cardiovascular diseases. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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12 pages, 2404 KiB

Open AccessArticle

Synthesis of Marine Cyclopeptide Galaxamide Analogues as Potential Anticancer Agents

by Daichun Li, Xiaojian Liao, Shenghui Zhong, Bingxin Zhao and Shihai Xu

Mar. Drugs 2022, 20(3), 158; https://doi.org/10.3390/md20030158 - 22 Feb 2022

Cited by 7 | Viewed by 2172

Abstract

In this paper, eight new galaxamide analogues (Z-1~Z-8) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT assays. The modified analogue Z-6 displayed broad spectrum cytotoxic activity [...] Read more.

In this paper, eight new galaxamide analogues (Z-1~Z-8) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT assays. The modified analogue Z-6 displayed broad spectrum cytotoxic activity toward each tested cell line with IC₅₀ values of 1.65 ± 0.30 (MCF-7), 2.91 ± 0.17 (HepG2), 4.59 ± 0.27 (MD-MBA-231), 5.69 ± 0.37 (Hela), and 5.96 ± 0.41 (A549) μg/mL, respectively. The galaxamides Z-3 and Z-6 induced concentration-dependent apoptosis of the MCF-7 cells after 72 h as evaluated by the flow cytometry experiment. The results showed that these compounds could induce MCF-7 cell apoptosis by arresting the G0/G1 phase of the cell cycle and finally achieving the effect of inhibiting the proliferation of MCF-7 cells. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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9 pages, 2343 KiB

Open AccessArticle

Citreobenzofuran D–F and Phomenone A–B: Five Novel Sesquiterpenoids from the Mangrove-Derived Fungus Penicillium sp. HDN13-494

by Qian Wu, Yimin Chang, Qian Che, Dehai Li, Guojian Zhang and Tianjiao Zhu

Mar. Drugs 2022, 20(2), 137; https://doi.org/10.3390/md20020137 - 13 Feb 2022

Cited by 17 | Viewed by 3119

Abstract

Five new sesquiterpenoids, citreobenzofuran D–F (1–3) and phomenone A–B (4–5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were [...] Read more.

Five new sesquiterpenoids, citreobenzofuran D–F (1–3) and phomenone A–B (4–5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E–F (2–3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 μM. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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18 pages, 5244 KiB

Open AccessArticle

Sdy-1 Executes Antitumor Activity in HepG2 and HeLa Cancer Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway

by Mengyu Sun, Dongdong Zhou, Jingwan Wu, Jing Zhou and Jing Xu

Mar. Drugs 2022, 20(2), 125; https://doi.org/10.3390/md20020125 - 5 Feb 2022

Cited by 5 | Viewed by 2953

Abstract

Demethylincisterol A₃ (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation [...] Read more.

Demethylincisterol A₃ (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation and migration of human liver (HepG2) and cervical cancer (HeLa) cells in vitro and it can induce cell apoptosis and arrest the cell cycle in the G1-phase. Mechanistically, we demonstrated that Sdy-1 executes its function via inhibition of the Wnt/β-catenin signaling pathway. Sdy-1 may not inhibit the Wnt signaling pathway through the cascade reaction from upstream to downstream, but directly acts on β-catenin to reduce its transcription level, thereby reducing the level of β-catenin protein and further reducing the expression of downstream related proteins. The possible interaction between Sdy-1 and β-catenin protein was further confirmed by molecular docking studies. In the nude mouse xenograft model, Sdy-1 can also significantly inhibit tumor growth. These results indicated that Sdy-1 is an efficient inhibitor of the Wnt signaling pathway and is a promising antitumor candidate for therapeutic applications. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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15 pages, 5158 KiB

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Molecular Details of Actinomycin D-Treated MRSA Revealed via High-Dimensional Data

by Xuewei Xia, Jun Liu, Li Huang, Xiaoyong Zhang, Yunqin Deng, Fengming Li, Zhiyuan Liu and Riming Huang

Mar. Drugs 2022, 20(2), 114; https://doi.org/10.3390/md20020114 - 31 Jan 2022

Cited by 6 | Viewed by 3741

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is highly concerning as a principal infection pathogen. The investigation of higher effective natural anti-MRSA agents from marine Streptomyces parvulus has led to the isolation of actinomycin D, that showed potential anti-MRSA activity with MIC and MBC values of [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) is highly concerning as a principal infection pathogen. The investigation of higher effective natural anti-MRSA agents from marine Streptomyces parvulus has led to the isolation of actinomycin D, that showed potential anti-MRSA activity with MIC and MBC values of 1 and 8 μg/mL, respectively. Proteomics-metabolomics analysis further demonstrated a total of 261 differential proteins and 144 differential metabolites induced by actinomycin D in MRSA, and the co-mapped correlation network of omics, indicated that actinomycin D induced the metabolism pathway of producing the antibiotic sensitivity in MRSA. Furthermore, the mRNA expression levels of the genes acnA, ebpS, clfA, icd, and gpmA related to the key differential proteins were down-regulated measured by qRT-PCR. Molecular docking predicted that actinomycin D was bound to the targets of the two key differential proteins AcnA and Icd by hydrogen bonds and interacted with multiple amino acid residues of the proteins. Thus, these findings will provide a basic understanding to further investigation of actinomycin D as a potential anti-MRSA agent. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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18 pages, 3786 KiB

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A Novel Peptide Derived from Arca inflata Induces Apoptosis in Colorectal Cancer Cells through Mitochondria and the p38 MAPK Pathway

by Chunlei Li, Sirui Zhang, Jianhua Zhu, Weijuan Huang, Yuanyuan Luo, Hui Shi, Dongbo Yu, Liguo Chen, Liyan Song and Rongmin Yu

Mar. Drugs 2022, 20(2), 110; https://doi.org/10.3390/md20020110 - 29 Jan 2022

Cited by 9 | Viewed by 4736

Abstract

Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine, Arca inflata Reeve. The full amino acid sequence and [...] Read more.

Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine, Arca inflata Reeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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17 pages, 6097 KiB

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Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure–Activity Relationships

by Rong Chao, Gulab Said, Qun Zhang, Yue-Xuan Qi, Jie Hu, Cai-Juan Zheng, Ji-Yong Zheng, Chang-Lun Shao, Guang-Ying Chen and Mei-Yan Wei

Mar. Drugs 2022, 20(2), 82; https://doi.org/10.3390/md20020082 - 18 Jan 2022

Cited by 7 | Viewed by 2981

Abstract

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2–37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the [...] Read more.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2–37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC₅₀ value of 89 μM, comparable to the positive control azadirachtin (IC₅₀ = 70 μM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15–4.93 μM. The preliminary structure–activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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15 pages, 1509 KiB

Open AccessArticle

Isoquinoline Alkaloids as Protein Tyrosine Phosphatase Inhibitors from a Deep-Sea-Derived Fungus Aspergillus puniceus

by Cheng-Mei Liu, Fei-Hua Yao, Xin-Hua Lu, Xue-Xia Zhang, Lian-Xiang Luo, Xiao Liang and Shu-Hua Qi

Mar. Drugs 2022, 20(1), 78; https://doi.org/10.3390/md20010078 - 17 Jan 2022

Cited by 20 | Viewed by 3104

Abstract

Puniceusines A–N (1–14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the [...] Read more.

Puniceusines A–N (1–14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3–5 and 8–13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC₅₀ values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC₅₀ value of 11.0 µM, and 14, which contained an active center, -C=N⁺, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1–14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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12 pages, 1693 KiB

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Chevalones H–M: Six New α-Pyrone Meroterpenoids from the Gorgonian Coral-Derived Fungus Aspergillus hiratsukae SCSIO 7S2001

by Xia-Yu Chen, Qi Zeng, Yu-Chan Chen, Wei-Mao Zhong, Yao Xiang, Jun-Feng Wang, Xue-Feng Shi, Wei-Min Zhang, Si Zhang and Fa-Zuo Wang

Mar. Drugs 2022, 20(1), 71; https://doi.org/10.3390/md20010071 - 14 Jan 2022

Cited by 11 | Viewed by 2644

Abstract

Six new α-pyrone meroterpenoid chevalones H–M (1–6), together with six known compounds (7–12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, [...] Read more.

Six new α-pyrone meroterpenoid chevalones H–M (1–6), together with six known compounds (7–12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1–5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25–100 μg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC₅₀ values of 12.75, 9.29, and 20.11 μM, respectively. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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14 pages, 1916 KiB

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Sonneradon A Extends Lifespan of Caenorhabditis elegans by Modulating Mitochondrial and IIS Signaling Pathways

by Shu Jiang, Cui-Ping Jiang, Pei Cao, Yong-Hong Liu, Cheng-Hai Gao and Xiang-Xi Yi

Mar. Drugs 2022, 20(1), 59; https://doi.org/10.3390/md20010059 - 8 Jan 2022

Cited by 9 | Viewed by 3033

Abstract

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA [...] Read more.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA in antiaging remains unclear. In this article, we studied the function of SDA in antiaging by using the animal model Caenorhabditis elegans. Results showed that SDA inhibited production of reactive oxygen species (ROS) by 53%, and reduced the accumulation of aging markers such as lipids and lipofuscins. Moreover, SDA also enhanced the innate immune response to Pseudomonas aeruginosa infection. Genetic analysis of a series of mutants showed that SDA extended the lifespan of the mutants of eat-2 and glp-1. Together, this effect may be related to the enhanced resistance to oxidative stress via mitochondrial and insulin/insulin-like growth factor-1 signaling (IIS) pathways. The results of this study provided new evidence for an antiaging effect of SDA in C. elegans, as well as insights into the implication of antiaging activity of SDA in higher organisms. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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14 pages, 3644 KiB

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Mono- and Dimeric Xanthones with Anti-Glioma and Anti-Inflammatory Activities from the Ascidian-Derived Fungus Diaporthe sp. SYSU-MS4722

by Senhua Chen, Heng Guo, Minghua Jiang, Qilin Wu, Jing Li, Hongjie Shen and Lan Liu

Mar. Drugs 2022, 20(1), 51; https://doi.org/10.3390/md20010051 - 5 Jan 2022

Cited by 9 | Viewed by 2436

Abstract

Seven new xanthones, diaporthones A−G (1−7), together with 13 known analogues, including five mono- (8−14) and six dimeric xanthones (15−20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar [...] Read more.

Seven new xanthones, diaporthones A−G (1−7), together with 13 known analogues, including five mono- (8−14) and six dimeric xanthones (15−20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HR-ESIMS). The absolute configurations of 1−7 were clearly identified by X-ray crystallographic analysis and calculation of the ECD Spectra. Compounds 15−20 showed significant anti-inflammatory activity with IC₅₀ values between 6.3 and 8.0 μM. In addition, dimeric xanthones (15−20) showed selective cytotoxicity against T98G cell lines with IC₅₀ values ranging from 19.5 to 78.0 μM. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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18 pages, 5330 KiB

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Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, ADMET, and Molecular Dynamics (MD) Simulation of Potential Inhibitors of PD-L1 from the Library of Marine Natural Products

by Lianxiang Luo, Ai Zhong, Qu Wang and Tongyu Zheng

Mar. Drugs 2022, 20(1), 29; https://doi.org/10.3390/md20010029 - 25 Dec 2021

Cited by 45 | Viewed by 8451

Abstract

Background: In the past decade, several antibodies directed against the PD-1/PD-L1 interaction have been approved. However, therapeutic antibodies also exhibit some shortcomings. Using small molecules to regulate the PD-1/PD-L1 pathway may be another way to mobilize the immune system to fight cancer. Method: [...] Read more.

Background: In the past decade, several antibodies directed against the PD-1/PD-L1 interaction have been approved. However, therapeutic antibodies also exhibit some shortcomings. Using small molecules to regulate the PD-1/PD-L1 pathway may be another way to mobilize the immune system to fight cancer. Method: 52,765 marine natural products were screened against PD-L1(PDBID: 6R3K). To identify natural compounds, a structure-based pharmacophore model was generated, following by virtual screening and molecular docking. Then, the absorption, distribution, metabolism, and excretion (ADME) test was carried out to select the most suitable compounds. Finally, molecular dynamics simulation was also performed to validate the binding property of the top compound. Results: Initially, 12 small marine molecules were screened based on the pharmacophore model. Then, two compounds were selected for further evaluation based on the molecular docking scores. After ADME and toxicity studies, molecule 51320 was selected for further verification. By molecular dynamics analysis, molecule 51320 maintains a stable conformation with the target protein, so it has the chance to become an inhibitor of PD-L1. Conclusions: Through structure-based pharmacophore modeling, virtual screening, molecular docking, ADMET approaches, and molecular dynamics (MD) simulation, the marine natural compound 51320 can be used as a small molecule inhibitor of PD-L1. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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17 pages, 6510 KiB

Open AccessArticle

Actinomycin X2, an Antimicrobial Depsipeptide from Marine-Derived Streptomyces cyaneofuscatus Applied as a Good Natural Dye for Silk Fabric

by Wei Chen, Kaixiong Ye, Xiaoji Zhu, Huihui Zhang, Ranran Si, Jianing Chen, Zijun Chen, Kaili Song, Zhicheng Yu and Bingnan Han

Mar. Drugs 2022, 20(1), 16; https://doi.org/10.3390/md20010016 - 23 Dec 2021

Cited by 19 | Viewed by 4420

Abstract

Actinomycins as clinical medicine have been extensively studied, while few investigations were conducted to discover the feasibility of actinomycins as antimicrobial natural dye contributing to the medical value of the functional fabrics. This study was focused on the application of actinomycin X2 (Ac.X2), [...] Read more.

Actinomycins as clinical medicine have been extensively studied, while few investigations were conducted to discover the feasibility of actinomycins as antimicrobial natural dye contributing to the medical value of the functional fabrics. This study was focused on the application of actinomycin X2 (Ac.X2), a peptide pigment cultured from marine-derived Streptomyces cyaneofuscatus, in the dyeing and finishing of silk fabric. The dyeing potential of Ac.X2 with silk vs. cotton fabrics was assessed. As a result, the silk fabric exhibited greater uptake and color fastness with Ac.X2. Through Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analyses, some changes of chemical property for the dyed fabric and Ac.X2 were studied. The silk fabric dyed with Ac.X2 exhibited good UV protection ability. The antibacterial properties of dyed and finished silk were also evaluated, which exhibited over 90% antibacterial activity even after 20 washing cycles. In addition, the brine shrimp assay was conducted to evaluate the general toxicity of the tested fabric, and the results indicated that the dyed silk fabrics had a good biological safety property. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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13 pages, 1886 KiB

Open AccessArticle

Pharmacokinetics and Metabolism Study of Deep-Sea-Derived Butyrolactone I in Rats by UHPLC–MS/MS and UHPLC–Q-TOF-MS

by Liang Wu, Chun-Lan Xie, Xian-Wen Yang and Gang Chen

Mar. Drugs 2022, 20(1), 11; https://doi.org/10.3390/md20010011 - 22 Dec 2021

Cited by 7 | Viewed by 3097

Abstract

Butyrolactone I (BTL-I) is a butanolide isolated from the deep-sea-derived fungus, Aspergillus sp. It provides a potential new target for the prevention and treatment of food allergies. This study aimed to investigate the metabolic and pharmacokinetic profile of BTL-I in rats. The metabolic [...] Read more.

Butyrolactone I (BTL-I) is a butanolide isolated from the deep-sea-derived fungus, Aspergillus sp. It provides a potential new target for the prevention and treatment of food allergies. This study aimed to investigate the metabolic and pharmacokinetic profile of BTL-I in rats. The metabolic profiles were obtained by UHPLC–Q-TOF-MS. As a result, eleven metabolites were structurally identified, and the proposed metabolic pathways of BTL-I were characterized. The main metabolites were the oxidative and glucuronidative metabolites. In addition, a sensitive UHPLC–MS/MS method was established for the quantitation of BTL-I in rat plasma (LOQ = 2 ng/mL). The method was fully validated and successfully applied to the pharmacokinetic study of BTL-I in rats after oral administration or intravenous administration. The oral bioavailability was calculated as 6.29%, and the maximum plasma concentrations were 9.85 ± 1.54 ng/mL and 17.97 ± 1.36 ng/mL for intravenous and intragastric dosing groups, respectively. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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13 pages, 27455 KiB

Open AccessArticle

Protective Effect of Flavonoids from a Deep-Sea-Derived Arthrinium sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells

by Jia-Rong Hou, Yan-Hong Wang, Ying-Nan Zhong, Tong-Tong Che, Yang Hu, Jie Bao and Ning Meng

Mar. Drugs 2021, 19(12), 712; https://doi.org/10.3390/md19120712 - 18 Dec 2021

Cited by 16 | Viewed by 2934

Abstract

Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium [...] Read more.

Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium sp., 2,3,4,6,8-pentahydroxy-1-methylxanthone (compound 1) and arthone C (compound 2) effectively scavenged ROS in vitro. In this study, we further investigated whether these compounds could protect against ox-LDL-induced oxidative injury in endothelial cells and the underlying mechanisms. Our results showed that compounds 1 and 2 inhibited ox-LDL-induced apoptosis and adhesion factors expression in human umbilical vein vascular endothelial cells (HUVECs). Mechanistic studies showed that these compounds significantly inhibited the ROS level increase and the NF-κB nuclear translocation induced by ox-LDL. Moreover, compounds 1 and 2 activated the Nrf2 to transfer into nuclei and increased the expression of its downstream antioxidant gene HO-1 by inducing the phosphorylation of AKT in HUVECs. Importantly, the AKT inhibitor MK-2206 2HCl or knockdown of Nrf2 by RNA interference attenuated the inhibition effects of these compounds on ox-LDL-induced apoptosis in HUVECs. Meanwhile, knockdown of Nrf2 abolished the effects of the compounds on ox-LDL-induced ROS level increase and the translocation of NF-κB to nuclei. Collectively, the data showed that compounds 1 and 2 protected endothelial cells against ox-LDL-induced oxidative stress through activating the AKT/Nrf2/HO-1 pathway. Our study provides new strategies for the design of lead compounds for related cardiovascular diseases treatment. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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12 pages, 1931 KiB

Open AccessArticle

Cyclic Peptides from the Soft Coral-Derived Fungus Aspergillus sclerotiorum SCSIO 41031

by Jieyi Long, Yaqi Chen, Weihao Chen, Junfeng Wang, Xuefeng Zhou, Bin Yang and Yonghong Liu

Mar. Drugs 2021, 19(12), 701; https://doi.org/10.3390/md19120701 - 10 Dec 2021

Cited by 11 | Viewed by 3192

Abstract

Three novel cyclic hexapeptides, sclerotides C–E (1–3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus [...] Read more.

Three novel cyclic hexapeptides, sclerotides C–E (1–3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus sclerotiorum SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey’s method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (4) exhibited acetylcholinesterase inhibitory activity with an IC₅₀ value of 15.6 μM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC₅₀ value of 10.1 μM. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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14 pages, 2024 KiB

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Heterocornols from the Sponge-Derived Fungus Pestalotiopsis heterocornis with Anti-Inflammatory Activity

by Hui Lei, Xiaoxu Bi, Xiuping Lin, Jianglian She, Xiaowei Luo, Hong Niu, Dan Zhang and Bin Yang

Mar. Drugs 2021, 19(11), 585; https://doi.org/10.3390/md19110585 - 20 Oct 2021

Cited by 16 | Viewed by 2412

Abstract

One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, [...] Read more.

One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, including eight new polyketide derivatives, heterocornols Q–X (1–8), one new ceramide (9), and three known analogues (10–12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data and calculated ECD analysis. Heterocornols Q (1) and R (2) are novel 6/5/7/5 tetracyclic polyketide derivatives featuring dihydroisobenzofuran and benzo-fused dioxabicyclo [4.2.1] nonane system, which might be derived from the acetyl-CoA by epoxidation, polyene cyclization, and rearrangement to form the core skeleton. Compound 12 showed moderate or weak antimicrobial activities against with MIC values ranging from 25 to 100 μg/mL. Heterocornols T and X (7 and 8) could inhibit the production of LPS-induced NO significantly, comparable to dexamethasone. Further Western blotting analysis showed 7 and 8 markedly suppressed the iNOS protein expression in LPS-induced RAW 264.7 cells in a dose-dependent manner. The result showed that 7 and 8 might serve as potential leads for development of anti-inflammatory activity. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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14 pages, 1998 KiB

Open AccessArticle

Cytotoxic Minor Piericidin Derivatives from the Actinomycete Strain Streptomyces psammoticus SCSIO NS126

by Kunlong Li, Ziqi Su, Yongli Gao, Xiuping Lin, Xiaoyan Pang, Bin Yang, Huaming Tao, Xiaowei Luo, Yonghong Liu and Xuefeng Zhou

Mar. Drugs 2021, 19(8), 428; https://doi.org/10.3390/md19080428 - 28 Jul 2021

Cited by 16 | Viewed by 2829

Abstract

The mangrove-sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126 was found to have productive piericidin metabolites featuring anti-renal cell carcinoma activities. In this study, in order to explore more diverse piericidin derivatives, and therefore to discover superior anti-tumor lead compounds, the NS126 strain [...] Read more.

The mangrove-sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126 was found to have productive piericidin metabolites featuring anti-renal cell carcinoma activities. In this study, in order to explore more diverse piericidin derivatives, and therefore to discover superior anti-tumor lead compounds, the NS126 strain was further fermented at a 300-L scale under optimized fermentation conditions. As a result, eight new minor piericidin derivatives (piericidins L-R (1–7) and 11-demethyl-glucopiericidin A (8)) were obtained, along with glucopiericidin B (9). The new structures including absolute configurations were determined by spectroscopic methods coupled with experimental and calculated electronic circular dichroism. We also proposed plausible biosynthetic pathways for these unusual post-modified piericidins. Compounds 1 and 6 showed selective cytotoxic activities against OS-RC-2 cells, and 2–5 exhibited potent cytotoxicity against HL-60 cells, with IC₅₀ values lower than 0.1 μM. The new piericidin glycoside 8 was cytotoxic against ACHN, HL-60 and K562, with IC₅₀ values of 2.3, 1.3 and 5.5 μM, respectively. The ability to arrest the cell cycle and cell apoptosis effects induced by 1 and 6 in OS-RC-2 cells, 2 in HL-60 cells, and 8 in ACHN cells were then further investigated. This study enriched the structural diversity of piericidin derivatives and confirmed that piericidins deserve further investigations as promising anti-tumor agents. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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15 pages, 2584 KiB

Open AccessArticle

Large-Scale Plasma Peptidomic Profiling Reveals a Novel, Nontoxic, Crassostrea hongkongensis-Derived Antimicrobial Peptide against Foodborne Pathogens

by Fan Mao, Yongbo Bao, Nai-Kei Wong, Minwei Huang, Kunna Liu, Xiangyu Zhang, Zhuo Yang, Wenjie Yi, Xiao Shu, Zhiming Xiang, Ziniu Yu and Yang Zhang

Mar. Drugs 2021, 19(8), 420; https://doi.org/10.3390/md19080420 - 26 Jul 2021

Cited by 14 | Viewed by 2643

Abstract

Antimicrobial peptides are a fundamental component of mollusks’ defense systems, though they remain a thinly investigated subject. Here, infection by Vibrio parahemolyticus triggered a significant increase in antimicrobial activity in oyster plasma. By using PBS-challenged oysters as a control, plasma peptides from immunologically [...] Read more.

Antimicrobial peptides are a fundamental component of mollusks’ defense systems, though they remain a thinly investigated subject. Here, infection by Vibrio parahemolyticus triggered a significant increase in antimicrobial activity in oyster plasma. By using PBS-challenged oysters as a control, plasma peptides from immunologically challenged oysters were subjected to peptidomic profiling and in silico data mining to identify bioactive peptides. Thirty-five identified plasma peptides were up-regulated post infection, among which, six up-regulated peptides (URPs) showed a relatively high positive charge. URP20 was validated with significant antibacterial activity. Virtually, URP20 triggered aggregation of bacterial cells, accompanied by their membrane permeabilization. Interestingly, URP20 was found to be active against Gram-positive and Gram-negative foodborne pathogens as well as Candida albicans, with no cytotoxicity to mammalian cells and mice. Our study provides the first large-scale plasma peptidomic dataset that identifies novel bioactive peptides in marine mollusks. Further exploration of peptide diversity in marine invertebrates should prove a fruitful pursuit for designing novel AMPs with broad applications. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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18 pages, 4946 KiB

Open AccessArticle

Purification, Identification, Activity Evaluation, and Stability of Antioxidant Peptides from Alcalase Hydrolysate of Antarctic Krill (Euphausia superba) Proteins

by Shuang-Yi Zhang, Guo-Xu Zhao, Shi-Kun Suo, Yu-Mei Wang, Chang-Feng Chi and Bin Wang

Mar. Drugs 2021, 19(6), 347; https://doi.org/10.3390/md19060347 - 17 Jun 2021

Cited by 44 | Viewed by 3906

Abstract

For utilizing the largest source of marine proteins, Antarctic krill (Euphausia superba) proteins were defatted and hydrolyzed separately using pepsin, alcalase, papain, trypsin, and netrase, and alcalase hydrolysate (EPAH) showed the highest DPPH radical (DPPH·) and hydroxyl radical (HO·) scavenging activity [...] Read more.

For utilizing the largest source of marine proteins, Antarctic krill (Euphausia superba) proteins were defatted and hydrolyzed separately using pepsin, alcalase, papain, trypsin, and netrase, and alcalase hydrolysate (EPAH) showed the highest DPPH radical (DPPH·) and hydroxyl radical (HO·) scavenging activity among five hydrolysates. Using ultrafiltration and chromatography methods, fifteen antioxidant peptides were purified from EPAH and identified as Asn-Gln-Met (NQM), Trp-Phe-Pro-Met (WFPM), Gln-Asn-Pro-Thr (QNPT), Tyr-Met-Asn-Phe (YMNF), Ser-Gly-Pro-Ala (SGPA), Ser-Leu-Pro-Tyr (SLPY), Gln-Tyr-Pro-Pro-Met-Gln-Tyr (QYPPMQY), Glu-Tyr-Glu-Ala (EYEA), Asn-Trp-Asp-Asp-Met-Arg-Ile-Val-Ala-Val (NWDDMRIVAV), Trp-Asp-Asp-Met-Glu-Arg-Leu-Val-Met-Ile (WDDMERLVMI), Asn-Trp-Asp-Asp-Met-Glu-Pro-Ser-Phe (NWD-DMEPSF), Asn-Gly-Pro-Asp-Pro-Arg-Pro-Ser-Gln-Gln (NGPDPRPSQQ), Ala-Phe-Leu-Trp-Asn (AFLWA), Asn-Val-Pro-Asp-Met (NVPDM), and Thr-Phe-Pro-Ile-Tyr-Asp-Tyr-Pro-Gln (TFPIYDPQ), respectively, using a protein sequencer and ESI/MS. Among fifteen antioxidant peptides, SLPY, QYPPMQY and EYEA showed the highest scavenging activities on DPPH· (EC₅₀ values of 1.18 ± 0.036, 1.547 ± 0.150, and 1.372 ± 0.274 mg/mL, respectively), HO· (EC₅₀ values of 0.826 ± 0.027, 1.022 ± 0.058, and 0.946 ± 0.011 mg/mL, respectively), and superoxide anion radical (EC₅₀ values of 0.789 ± 0.079, 0.913 ± 0.007, and 0.793 ± 0.056 mg/mL, respectively). Moreover, SLPY, QYPPMQY and EYEA showed strong reducing power, protective capability against H₂O₂-damaged plasmid DNA, and lipid peroxidation inhibition ability. Furthermore, SLPY, QYPPMQY, and EYEA had high stability under temperatures lower than 80 °C, pH values ranged from 6–8, and simulated GI digestion for 180 min. The results showed that fifteen antioxidant peptides from alcalase hydrolysate of Antarctic krill proteins, especially SLPY, QYPPMQY and EYEA, might serve as effective antioxidant agents applied in food and health products. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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Secondary Metabolites from Marine Sponges of the Genus Oceanapia: Chemistry and Biological Activities

by Meng-Juan Xu, Lin-Jing Zhong, Jun-Kun Chen, Qing Bu and Lin-Fu Liang

Mar. Drugs 2022, 20(2), 144; https://doi.org/10.3390/md20020144 - 16 Feb 2022

Cited by 6 | Viewed by 3473

Abstract

In this review, we summarized the distribution of the chemically investigated Oceanapia sponges, including the isolation and biological activities of their secondary metabolites, covering the literature from the first report in 1989 to July 2019. There have been 110 compounds reported during this [...] Read more.

In this review, we summarized the distribution of the chemically investigated Oceanapia sponges, including the isolation and biological activities of their secondary metabolites, covering the literature from the first report in 1989 to July 2019. There have been 110 compounds reported during this period, including 59 alkaloids, 33 lipids, 14 sterols and 4 miscellaneous compounds. Besides their unique structures, they exhibited promising bioactivities ranging from insecticidal to antibacterial. Their complex structural characteristics and diverse biological properties have attracted a great deal of attention from chemists and pharmaceuticals seeking to perform their applications in the treatment of disease. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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