N-Arylsulfonylated C-Homoaporphines as a New Class of Antiplatelet and Antimicrobial Agents.

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-12-23 eCollection Date: 2025-01-09 DOI:10.1021/acsmedchemlett.4c00491

Bharti Rajesh Kumar Shyamlal, Amol T Mahajan, Vikash Kumar, Aarohi Gupta, Rishabh Shrivastava Ronin, Manas Mathur, Janmejaya Sen, Sandeep Chaudhary

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Abstract

A series of novel N-arylsulfonylated C-homoaporphine alkaloids were synthesized under microwave irradiation and evaluated for their in vitro antiplatelet and antimicrobial activities. Among the series, compounds 12a, 12c, 12e, 12f, 12h, 12j, 12k, 12m, and 12o demonstrated highly potent (∼3-fold) platelet aggregation inhibitory activity than acetylsalicylic acid (IC₅₀ = 21.34 μg/mL). Several N-arylsulfonylated C-homoaporphines also exhibited promising antimicrobial activity against various strains, including Macrophoma phaseolina, Trichoderma reesei, and Aspergillus niger, with minimum inhibitory concentrations (MIC) of 12.5, 6.25, and 12.5 μg/mL, respectively, comparable to Ketoconazole [MIC = 12.5 μg/mL (MP and AN strain); 6.25 μg/mL (TR strain)]. 12h showed potent antibacterial activity (IC₅₀ = 6.25 μg/mL against Escherichia coli and Bacillus subtilis) compared to Ampicillin (IC₅₀ = 12.5 μg/mL). After thorough structure-activity relationship (SAR) and in silico studies, C-homoaporphines were identified as a novel class of antiplatelet and antimicrobial agents.

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n -芳基磺酰化c -同源阿啡作为一类新的抗血小板和抗菌药物。

在微波辐照下合成了一系列新型n -芳基磺化C-homoaporphine生物碱，并对其体外抗血小板和抗菌活性进行了评价。其中，化合物12a、12c、12e、12f、12h、12j、12k、12m和12o比乙酰水杨酸具有更强的抑制血小板聚集活性（IC50 = 21.34 μg/mL）（约3倍）。几种n -芳基磺化的c -同型萘啡对菜绿大瘤、里氏木霉和黑曲霉等多种菌株也表现出良好的抑菌活性，其最低抑菌浓度（MIC）分别为12.5、6.25和12.5 μg/mL，与酮康唑[MIC = 12.5 μg/mL （MP和AN菌株）]相当；6.25 μg/mL （TR菌株）]。与氨苄西林（IC50 = 12.5 μg/mL）相比，12h对大肠杆菌和枯草芽孢杆菌具有较强的抑菌活性（IC50 = 6.25 μg/mL）。经过深入的构效关系（SAR）和硅研究，C-homoaporphines被确定为一类新的抗血小板和抗菌药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.