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11 pages, 2363 KB

Open AccessArticle

Novel Derivatives of Nitrobenzofurazan with Chromogenic and Fluorogenic Properties

by Alexandru Bujor, Anamaria Hanganu, Rodica Baratoiu, Elena N. Hristea, Madalina Tudose, Victorita Tecuceanu, Augustin M. Madalan and Petre Ionita

Molecules 2023, 28(16), 6146; https://doi.org/10.3390/molecules28166146 - 20 Aug 2023

Viewed by 2028

Abstract

Five new derivatives were obtained utilizing 4-chloro-7-nitrobenzofurazan (NBD-chloride) in combination with furfurylamine, adamantylamine, aminohippuric acid, phenylalanine, and dehydroabietylamine. These derivatives were then subjected to a comparative analysis of their physical, chemical, and certain biological properties alongside two analogous and known compounds derived from [...] Read more.

Five new derivatives were obtained utilizing 4-chloro-7-nitrobenzofurazan (NBD-chloride) in combination with furfurylamine, adamantylamine, aminohippuric acid, phenylalanine, and dehydroabietylamine. These derivatives were then subjected to a comparative analysis of their physical, chemical, and certain biological properties alongside two analogous and known compounds derived from the glycine and 4-amino-TEMPO free radical. Full article

(This article belongs to the Special Issue Synthesis and Biologically Relevant Heterocyclic Compounds)

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15 pages, 1349 KB

Open AccessArticle

Tricyclic Diterpenoids Selectively Suppress Androgen Receptor-Positive Prostate Cancer Cells

by Inderpal Sekhon, Guanglin Chen, Keyara Piri, Seiji Shinkawa, Dennis Ashong, Qiang Zhang, Guangdi Wang and Qiao-Hong Chen

Molecules 2023, 28(12), 4743; https://doi.org/10.3390/molecules28124743 - 13 Jun 2023

Cited by 4 | Viewed by 2545

Abstract

Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective [...] Read more.

Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective in CRPC with AR gene amplification, LBD mutation, and the evolution of LBD-truncated AR splice variants. Encouraged by the fact that tricyclic aromatic diterpenoid QW07 has recently been established as a potential N-terminal AR antagonist, this study aims to explore the structure–activity relationship of tricyclic diterpenoids and their potential to suppress AR-positive cell proliferation. Dehydroabietylamine, abietic acid, dehydroabietic acid, and their derivatives were selected, since they have a similar core structure as QW07. Twenty diterpenoids were prepared for the evaluation of their antiproliferative potency on AR-positive prostate cancer cell models (LNCaP and 22Rv1) using AR-null cell models (PC-3 and DU145) as comparisons. Our data indicated that six tricyclic diterpenoids possess greater potency than enzalutamide (FDA-approved AR antagonist) towards LNCaP and 22Rv1 AR-positive cells, and four diterpenoids are more potent than enzalutamide against 22Rv1 AR-positive cells. The optimal derivative possesses greater potency (IC₅₀ = 0.27 µM) and selectivity than QW07 towards AR-positive 22Rv1 cells. Full article

(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation III)

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11 pages, 1676 KB

Open AccessArticle

Anticoronavirus Evaluation of Antimicrobial Diterpenoids: Application of New Ferruginol Analogues

by Mihayl Varbanov, Stéphanie Philippot and Miguel A. González-Cardenete

Viruses 2023, 15(6), 1342; https://doi.org/10.3390/v15061342 - 9 Jun 2023

Cited by 8 | Viewed by 2227

Abstract

The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were [...] Read more.

The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals. Full article

(This article belongs to the Special Issue Novel Antiviral Agents: Synthesis, Molecular Modelling Studies and Biological Investigation)

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11 pages, 9507 KB

Open AccessArticle

Discovery of Novel Bioactive Tanshinones and Carnosol Analogues against Breast Cancer

by Miguel A. González-Cardenete, Natalia González-Zapata, Lucinda Boyd and Fatima Rivas

Cancers 2023, 15(4), 1318; https://doi.org/10.3390/cancers15041318 - 19 Feb 2023

Cited by 10 | Viewed by 3619

Abstract

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of [...] Read more.

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC₅₀ in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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16 pages, 1936 KB

Open AccessArticle

Chiral Quaternary Ammoniums Derived from Dehydroabietylamine: Synthesis and Application to Alkynylation of Isatin Derivatives Catalyzed by Silver

by Guanyu Jiang, Xinduo Sun, Fanrui Zhou, Kun Liang and Qian Chen

Catalysts 2021, 11(12), 1479; https://doi.org/10.3390/catal11121479 - 3 Dec 2021

Cited by 4 | Viewed by 3816

Abstract

Abietic acid and its derivatives have broadly been used in fine chemicals and are renewable resources. Its inherent chiral rigid tricyclic phenanthrene skeleton is unique. Its utilities in asymmetric catalysis remain to be explored. A series new amide-type chiral quaternary ammoniums bearing dehydroabietylamine [...] Read more.

Abietic acid and its derivatives have broadly been used in fine chemicals and are renewable resources. Its inherent chiral rigid tricyclic phenanthrene skeleton is unique. Its utilities in asymmetric catalysis remain to be explored. A series new amide-type chiral quaternary ammoniums bearing dehydroabietylamine were designed, and prepared by two convenient steps. Acylation of dehydroabietylamine with bromoacetyl chloride afforded amide holding bromoacetyl group in higher yields using triethyl amine as base. Subsequent quaternization reaction gave the desired amide-type chiral quaternary ammoniums. The new chiral quaternary ammoniums can be used as phase-transfer catalyst (PTC) for the transition metal-catalysed alkynylation of isatin derivatives. Full article

(This article belongs to the Special Issue Heterogeneous/Homogeneous Catalysis in Organic Synthesis – Recent Advances)

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6 pages, 653 KB

Open AccessProceeding Paper

Development and Optimization of the Multi-Gram Synthesis of the Antiviral 18-(Phthalimide-2-yl)ferruginol

by Francisco Javier Miquel-Leal, Natalia González-Zapata, Orlando José Jimenez-Jarava, Yaneth M. Brand, Liliana Betancur-Galvis, Maria Luisa Marín and Miguel A. González-Cardenete

Chem. Proc. 2022, 8(1), 2; https://doi.org/10.3390/ecsoc-25-11667 - 13 Nov 2021

Viewed by 1691

Abstract

Virus-induced diseases are very common in our society, and we continuously need new treatments for these challenging infections. We discovered by serendipity some years ago that the molecule 18-(Phthalimide-2-yl)ferruginol, an analogue of the natural diterpenoid (+)-ferruginol, a pharmacologically active molecule, was able to [...] Read more.

Virus-induced diseases are very common in our society, and we continuously need new treatments for these challenging infections. We discovered by serendipity some years ago that the molecule 18-(Phthalimide-2-yl)ferruginol, an analogue of the natural diterpenoid (+)-ferruginol, a pharmacologically active molecule, was able to inhibit the spread of dengue virus type-2 (DENV-2) and human herpes virus 1 and 2 (HHV-1 and HHV-2). During the development and further study of the above-mentioned analogue, we required the scaling-up of the semisynthesis of the target molecule. The synthesis was already reported by Waldvogel and co-workers in 2007, starting from the commercially available ca. 60% (+)-dehydroabietylamine. In this communication, we describe the several issues that we faced and propose an optimized experimental procedure in order to obtain this broad-spectrum antiviral, which we found is even active against several strains of Zika virus. Full article

(This article belongs to the Proceedings of The 25th International Electronic Conference on Synthetic Organic Chemistry)

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14 pages, 3877 KB

Open AccessArticle

Synthesis of Tertiary and Quaternary Amine Derivatives from Wood Resin as Chiral NMR Solvating Agents

by Tiina Laaksonen, Sami Heikkinen and Kristiina Wähälä

Molecules 2015, 20(11), 20873-20886; https://doi.org/10.3390/molecules201119732 - 23 Nov 2015

Cited by 12 | Viewed by 8827

Abstract

Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher’s acid (3) and its n-Bu₄N salt (4)] [...] Read more.

Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher’s acid (3) and its n-Bu₄N salt (4)] (guests) by (+)-dehydroabietyl-N,N-dimethylmethanamine (5) and its ten different ammonium salts (hosts) was studied. The best results with 3 were obtained using 5 while with 4 the best enantiomeric resolution was obtained using (+)-dehydroabietyl-N,N-dimethylmethanaminium bis(trifluoromethane-sulfonimide) (6). The compounds 5 and 6 showed a 1:1 complexation behaviour between the host and guest. The capability of 5 and 6 to recognize the enantiomers of various α-substituted carboxylic acids and their n-Bu₄N salts in enantiomeric excess (ee) determinations was demonstrated. A modification of the RES-TOCSY NMR pulse sequence is described, allowing the enhancement of enantiomeric discrimination when the resolution of multiplets is insufficient. Full article

(This article belongs to the Section Organic Chemistry)

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19 pages, 435 KB

Open AccessArticle

(+)-Dehydroabietic Acid, an Abietane-Type Diterpene, Inhibits Staphylococcus aureus Biofilms in Vitro

by Adyary Fallarero, Malena Skogman, Janni Kujala, Mohanathas Rajaratnam, Vânia M. Moreira, Jari Yli-Kauhaluoma and Pia Vuorela

Int. J. Mol. Sci. 2013, 14(6), 12054-12072; https://doi.org/10.3390/ijms140612054 - 5 Jun 2013

Cited by 54 | Viewed by 9399

Abstract

Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed [...] Read more.

Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates. Full article

(This article belongs to the Section Biochemistry)

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10 pages, 347 KB

Open AccessArticle

Synthesis and NMR Spectral Studies of the 7-C₆₀-Adduct of N,N-(Tetrachlorophthaloyl) Dehydroabietylamine

by Zhi Zhou and Zhongxiang Lin

Molecules 2012, 17(4), 4209-4218; https://doi.org/10.3390/molecules17044209 - 5 Apr 2012

Cited by 3 | Viewed by 7837

Abstract

The 7-C₆₀-adduct of N,N-(tetrachlorophthaloyl)dehydroabietylamine was synthesized for the first time and characterized by IR, UV-vis, mass and NMR spectral studies. The ¹H-NMR and ¹³C-NMR resonance signals of the new compound are unambiguously assigned by using homo- [...] Read more.

The 7-C₆₀-adduct of N,N-(tetrachlorophthaloyl)dehydroabietylamine was synthesized for the first time and characterized by IR, UV-vis, mass and NMR spectral studies. The ¹H-NMR and ¹³C-NMR resonance signals of the new compound are unambiguously assigned by using homo- and heteronuclear 2D NMR spectroscopic techniques such as COSY, ROESY, HSQC and HMBC. The C₁ symmetric structure with 6,6-junction of compound was determined. Full article

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