المؤلفون: Muhammad Patel, Gopal Avashthi, Amel Gacem, Mohammed S. Alqahtani, Hyun-Kyung Park, Byong-Hun Jeon

المصدر: Molecules; Volume 28; Issue 14; Pages: 5490

مصطلحات موضوعية: benzimidazole, heterocyclic derivatives, biological activity

جغرافية الموضوع: agris

الوصف: Heterocyclic compounds are significant lead drug candidates based on their various structure–activity relationships (SAR), and their use in pharmaceutics is constantly developing. Benzimidazole (BnZ) is synthesized by a condensation reaction between benzene and imidazole. The BnZ structure consists of two nitrogen atoms embedded in a five-membered imide ring which is fused with a benzene ring. This review examines the conventional and green synthesis of metallic and non-metallic BnZ and their derivatives, which have several potential SARs, along with a wide range of pharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, anti-tubercular, and anti-protozoal properties. These compounds have been proven by pharmacological investigations to be efficient against different strains of microbes. Therefore, in this review, the structural variations of BnZ are listed along with various applications, predominantly related to their biological activities.

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العلاقة: Organic Chemistry; https://dx.doi.org/10.3390/molecules28145490Test

الإتاحة: https://doi.org/10.3390/molecules28145490Test

المؤلفون: Federica Sipala, Gianfranco Cavallaro, Giuseppe Forte, Cristina Satriano, Alessandro Giuffrida, Aurore Fraix, Angelo Spadaro, Salvatore Petralia, Carmela Bonaccorso, Cosimo Gianluca Fortuna, Simone Ronsisvalle

المصدر: Molecules; Volume 28; Issue 9; Pages: 3908

مصطلحات موضوعية: SARS-CoV-2, molecular modeling, heterocyclic derivatives

جغرافية الموضوع: agris

الوصف: Over the last few years, the study of the SARS-CoV-2 spike protein and its mutations has become essential in understanding how it interacts with human host receptors. Since the crystallized structure of the spike protein bound to the angiotensin-converting enzyme 2 (ACE2) receptor was released (PDB code 6M0J), in silico studies have been performed to understand the interactions between these two proteins. Specifically, in this study, heterocyclic compounds with different chemical characteristics were examined to highlight the possibility of interaction with the spike protein and the disruption of the interaction between ACE2 and the spike protein. Our results showed that these compounds interacted with the spike protein and interposed in the interaction zone with ACE2. Although further studies are needed, this work points to these heterocyclic push–pull compounds as possible agents capable of interacting with the spike protein, with the potential for the inhibition of spike protein–ACE2 binding.

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العلاقة: Medicinal Chemistry; https://dx.doi.org/10.3390/molecules28093908Test

الإتاحة: https://doi.org/10.3390/molecules28093908Test

المؤلفون: Ewa Bębenek, Elwira Chrobak, Zuzanna Rzepka, Dorota Wrześniok

المصدر: Biomolecules; Volume 12; Issue 10; Pages: 1540

مصطلحات موضوعية: pentacyclic triterpenes, heterocyclic derivatives, anticancer activity

جغرافية الموضوع: agris

الوصف: As part of the search for new medicinal substances with potential application in oncology, the synthesis of new compounds combining the betulin molecule and the indole system was carried out. The structure of the ester derivatives obtained in the Steglich reaction was confirmed by spectroscopic methods (1H and 13C NMR, HR-MS). The obtained new 3-indolyl betulin derivatives were evaluated for anticancer activity against several human cancer cell lines (melanomas, breast cancers, colorectal adenocarcinomas, lung cancer) as well as normal human fibroblasts. The significant reduction in MCF-7 cells viability for 28-hydroxy-(lup-20(29)-ene)-3-yl 2-(1H-indol-3-yl)acetate was observed at a concentration of 10 µg/mL (17 µM). In addition, cytometric analysis showed that this compound strongly reduces the proliferation rate of breast cancer cells. For this, the derivative showing the promising cytotoxic effect on MCF-7 breast cancer cells, the pharmacokinetic profile prediction was performed using in silico methods. Based on the results obtained in the study, it can be concluded that indole-functionalized triterpene EB367 is a promising starting point for further research in the field of breast cancer therapy or the synthesis of new derivatives.

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العلاقة: Natural and Bio-inspired Molecules; https://dx.doi.org/10.3390/biom12101540Test

الإتاحة: https://doi.org/10.3390/biom12101540Test

المؤلفون: Paweł Kozyra, Danuta Krasowska, Monika Pitucha

المصدر: International Journal of Molecular Sciences; Volume 23; Issue 11; Pages: 6084

مصطلحات موضوعية: melanoma, targeted therapy, anticancer activity, ion channels, BRAF kinase, MAPK pathway, PI3K–AKT pathway, heterocyclic derivatives, cancer

جغرافية الموضوع: agris

الوصف: Malignant melanoma (MM) is the most lethal skin cancer. Despite a 4% reduction in mortality over the past few years, an increasing number of new diagnosed cases appear each year. Long-term therapy and the development of resistance to the drugs used drive the search for more and more new agents with anti-melanoma activity. This review focuses on the most recent synthesized anti-melanoma agents from 2020–2022. For selected agents, apart from the analysis of biological activity, the structure–activity relationship (SAR) is also discussed. To the best of our knowledge, the following literature review delivers the latest achievements in the field of new anti-melanoma agents.

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العلاقة: Molecular Oncology; https://dx.doi.org/10.3390/ijms23116084Test

الإتاحة: https://doi.org/10.3390/ijms23116084Test

المؤلفون: Huu Tam Tran, Oanh Nhu Thi Vu, Thuy Nhu Thi Le, Bao Dam Chau Nguyen, Ngoc Nguyen Vo

المصدر: Applied Sciences; Volume 12; Issue 5; Pages: 2710

مصطلحات موضوعية: 4( 3H )-quinazolinone, heterocyclic derivatives, synthesize heterocyclic compounds

جغرافية الموضوع: agris

الوصف: The campaign “No action today, no cure tomorrow” against antimicrobial resistance proposed by the World Health Organization (WHO) has not only propeled people to take action to prevent antimicrobial resistance, but has also encouraged researchers to develop new antimicrobial agents. 4(3H)-quinazolinone and its derivatives belong to a group of compounds with many potential applications; this study was conducted to find new derivatives of heterocyclic 4(3H)-quinazolinone with biological effects, contributing to research on antibacterial and antifungal compounds. Using the closed-loop method between anthranilic acid and acetic anhydride, followed by reaction with aniline derivatives, a substituted product of position 3 of 4(3H)-quinazolinone was obtained, along with bromizing to replace the hydrogen of the methyl group in position 2 with dibromo. Heterocyclic derivatives such as imidazole, triazole, and thiazole were replaced from this dibromo product to obtain 19 derivatives. The structures of these derivatives were checked by modern methods such as IR, 1H-NMR, and MS. The results indicated that all of the structures were as expected, so the process of creating new derivatives from 4(3H)-quinazolinone was achieved in this study. Fourteen of the derivatives, namely 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3m, 3o, 3p, 3q, 3r, and 3s, had antibacterial or antifungal effects. Among these, there were five potential derivatives: Antifungal activity was observed on A. niger by 3j and 3f (MIC: 32 μg/mL) and 3s (MIC: 64 μg/mL), and on C. albicans by 3f (MIC: 8 μg/mL); antibacterial activity was observed on S. aureus by 3p (MIC: 16 μg/mL) and 3f and 3r (MIC: 32 μg/mL), on MRSA by 3f and 3r (MIC: 32 μg/mL), and on E. coli by 3f (MIC: 32 μg/mL).

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العلاقة: Biomedical Engineering; https://dx.doi.org/10.3390/app12052710Test

الإتاحة: https://doi.org/10.3390/app12052710Test

المؤلفون: Yuqin Yang, Tianxin Xie, Xuehao Tian, Nana Han, Xiaojing Liu, Hongshan Chen, Jinchai Qi, Feng Gao, Wen Li, Qianwen Wu, Su Huo, Yuhao Gu, Ziqi Dai, Penglong Wang, Haimin Lei

المصدر: Molecules; Volume 25; Issue 4; Pages: 948

مصطلحات موضوعية: betulinic acid, BA -nitrogen heterocyclic derivatives, antitumor, Hela, flow cytometry

جغرافية الموضوع: agris

الوصف: Betulinic acid (BA) is a star member of the pentacyclic triterpenoid family, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, 21 BA-nitrogen heterocyclic derivatives were synthetized, in addition to four intermediates, 23 of which were first reported. Moreover, they were screened for in-vitro cytotoxicity against four tumor cell lines (Hela, HepG-2, BGC-823 and SK-SY5Y) by a standard methylthiazol tetrazolium (MTT) assay. The majority of these derivatives showed much stronger cytotoxic activity than BA. Remarkably, the most potent compound 7e (the half maximal inhibitory concentration (IC50) of which was 2.05 ± 0.66 μM) was 12-fold more toxic in vitro than BA-treated Hela. Furthermore, multiple fluorescent staining techniques and flow cytometry collectively revealed that compound 7e could induce the early apoptosis of Hela cells. Structure–activity relationships were also briefly discussed. The present study highlighted the importance of introducing nitrogen heterocyclic rings into betulinic acid in the discovery and development of novel antitumor agents.

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العلاقة: https://dx.doi.org/10.3390/molecules25040948Test

الإتاحة: https://doi.org/10.3390/molecules25040948Test

المؤلفون: Daniela P. S. Alho, Jorge A. R. Salvador, Marta Cascante, Silvia Marin

المصدر: Molecules; Volume 24; Issue 4; Pages: 766

مصطلحات موضوعية: pentacyclic triterpenoids, glycyrrhetinic acid, heterocyclic derivatives, antiproliferative activity, apoptosis

جغرافية الموضوع: agris

الوصف: A new series of glycyrrhetinic acid derivatives has been synthesized via the introduction of different heterocyclic rings conjugated with an α,β-unsaturated ketone in its ring A. These new compounds were screened for their antiproliferative activity in a panel of nine human cancer cell lines. Compound 10 was the most active derivative, with an IC50 of 1.1 µM on Jurkat cells, which is 96-fold more potent than that of glycyrrhetinic acid, and was 4-fold more selective toward that cancer cell line. Further biological studies performed in Jurkat cells showed that compound 10 is a potent inducer of apoptosis that activates both the intrinsic and extrinsic pathways.

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العلاقة: Medicinal Chemistry; https://dx.doi.org/10.3390/molecules24040766Test

الإتاحة: https://doi.org/10.3390/molecules24040766Test

المؤلفون: Ricardo I. Rodríguez, José Alemán, Leonardo Mollari, Sergio Díaz-Tendero, Fernando Aguilar-Galindo

المصدر: Catalysts
Volume 11
Issue 8
Catalysts, Vol 11, Iss 922, p 922 (2021)

مصطلحات موضوعية: Imine, asymmetric synthesis, TP1-1185, radical–radical coupling, 010402 general chemistry, 01 natural sciences, Quantum chemistry, Catalysis, chemistry.chemical_compound, Computational chemistry, Physical and Theoretical Chemistry, QD1-999, Heterocyclic derivatives, radical addition, density functional theory, Process strategy, 010405 organic chemistry, Chemical technology, Enantioselective synthesis, pyrroline derivative, 0104 chemical sciences, Chemistry, chemistry, Coupling (computer programming), Mechanism (philosophy), photocatalysis, Knot (mathematics)

الوصف: A highly enantioselective protocol has been recently described as allowing the synthesis of five-membered cyclic imines harnessing the selective generation of a β-Csp3-centered radical of acyl heterocyclic derivatives and its subsequent interaction with diverse NH-ketimines. The overall transformation represents a novel cascade process strategy crafted by individual well-known steps
however, the construction of the new C-C bond highlights a crucial knot from a mechanistically perspective. We believe that the full understanding of this enigmatic step may enrich the current literature and expand latent future ideas. Therefore, a detailed mechanistic study of the protocol has been conducted. Here, we provide theoretical insight into the mechanism using quantum chemistry calculations. Two possible pathways have been investigated: (a) imine reduction followed by radical–radical coupling and (b) radical addition followed by product reduction. In addition, investigations to unveil the origin behind the enantioselectivity of the 1-pyrroline derivatives have been conducted as well.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::629bcd524ee582345c1b453816af0d23Test