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Keywords = streptochlorin

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14 pages, 3459 KiB  
Article
Design, Synthesis, Antifungal Activity, and Molecular Docking of Streptochlorin Derivatives Containing the Nitrile Group
by Jing-Rui Liu, Ya Gao, Bing Jin, Dale Guo, Fang Deng, Qiang Bian, Hai-Feng Zhang, Xin-Ya Han, Abdallah S. Ali, Ming-Zhi Zhang, Wei-Hua Zhang and Yu-Cheng Gu
Mar. Drugs 2023, 21(2), 103; https://doi.org/10.3390/md21020103 - 31 Jan 2023
Cited by 10 | Viewed by 3329
Abstract
Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could [...] Read more.
Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate—it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 μg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds. Full article
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13 pages, 6890 KiB  
Article
Discovery of Novel Pimprinine and Streptochlorin Derivatives as Potential Antifungal Agents
by Jing-Rui Liu, Jia-Mu Liu, Ya Gao, Zhan Shi, Ke-Rui Nie, Dale Guo, Fang Deng, Hai-Feng Zhang, Abdallah S. Ali, Ming-Zhi Zhang, Wei-Hua Zhang and Yu-Cheng Gu
Mar. Drugs 2022, 20(12), 740; https://doi.org/10.3390/md20120740 - 25 Nov 2022
Cited by 7 | Viewed by 3269
Abstract
Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this [...] Read more.
Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3′-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency. Full article
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13 pages, 2144 KiB  
Article
Efficient Preparation of Streptochlorin from Marine Streptomyces sp. SYYLWHS-1-4 by Combination of Response Surface Methodology and High-Speed Counter-Current Chromatography
by Lin Li, Shan He, Lijian Ding, Ye Yuan, Peng Zhu, Slava Epstein, Jianzhong Fan, Xiaokai Wu and Xiaojun Yan
Molecules 2016, 21(6), 693; https://doi.org/10.3390/molecules21060693 - 27 May 2016
Cited by 6 | Viewed by 4940
Abstract
Since first isolated from the lipophilic extract of Streptomyces sp. SF2583, streptochlorin, has attracted a lot of attention because of its various pharmacological properties, such as antibiotic, antiallergic, antitumor, and anti-inflammatory activities. For the efficient preparation of streptochlorin from a producing strain Streptomyces [...] Read more.
Since first isolated from the lipophilic extract of Streptomyces sp. SF2583, streptochlorin, has attracted a lot of attention because of its various pharmacological properties, such as antibiotic, antiallergic, antitumor, and anti-inflammatory activities. For the efficient preparation of streptochlorin from a producing strain Streptomyces sp. SYYLWHS-1-4, we developed a combinative method by using response surface methodology (RSM) and high-speed counter-current chromatography (HSCCC). In the fermentation process, we used RSM to optimize the condition for the efficient accumulation of streptochlorin, and the optimal parameters were: yeast extract 1.889 g/L, soluble starch 8.636 g/L, K2HPO4 0.359 g/L, CaCl2 2.5 g/L, MgSO4 0.625 g/L, marine salt 25 g/L, medium volume 50%, initial pH value 7.0, temperature 27.5 °C, which enhanced streptochlorin yield by 17.7-fold. During the purification process, the preparative HSCCC separation was performed using a petroleum ether–ethyl acetate–methanol–water (9:0.8:5:5, v/v/v/v) biphasic solvent system, where 300 mg of crude sample yielded 16.5 mg streptochlorin with over 95% purity as determined by UPLC. Consequently, the combination method provided a feasible strategy for highly effective preparation of streptochlorin, which ensured the supply of large amounts of streptochlorin for in vivo pharmacological assessments or other requirements. Full article
(This article belongs to the Section Natural Products Chemistry)
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9 pages, 1565 KiB  
Communication
Anti-Inflammatory Effect of Streptochlorin via TRIF-Dependent Signaling Pathways in Cellular and Mouse Models
by Do-Wan Shim, Hee Jae Shin, Ji-Won Han, Woo-Young Shin, Xiao Sun, Eun-Jeong Shim, Tack-Joong Kim, Tae-Bong Kang and Kwang-Ho Lee
Int. J. Mol. Sci. 2015, 16(4), 6902-6910; https://doi.org/10.3390/ijms16046902 - 26 Mar 2015
Cited by 10 | Viewed by 6650
Abstract
Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced [...] Read more.
Streptochlorin, a small compound derived from marine actinomycete, has been shown to have anti-angiogenic, anti-tumor, and anti-allergic activities. However, the anti-inflammatory effects and underlying mechanisms have not yet been reported. In the present study, we investigated the effect of streptochlorin on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Streptochlorin attenuated the production of proinflammatory mediators such as nitric oxide, cyclooxygenase-2, pro-interleukin (IL)-1β, and IL-6 in LPS-stimulated RAW264.7 cells through inhibition of the Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling pathway. Furthermore, streptochlorin suppressed the infiltration of immune cells such as neutrophils into the lung and proinflammatory cytokine production such as IL-6 and TNF-α in broncho-alveolar lavage fluid (BALF) in the LPS-induced acute lung injury (ALI) mouse model. Streptochlorin has potent anti-inflammatory effects through regulating TRIF-dependent signaling pathways, suggesting that streptochlorin may provide a valuable therapeutic strategy in treating various inflammatory diseases. Full article
(This article belongs to the Special Issue Bioactivity of Marine Natural Products)
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