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基于4-氨基香豆素的苯基碘鎓衍生物作为有效治疗剂的合成、生物学评价、药理学分析及分子对接研究

Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents.

作者信息

Zachariah Serin, M Shiji T, Vadakkadath Meethal Kannan, Jones Sara, Suchithra T V

机构信息

Department of Bioscience and Engineering, National Institute of Technology, Calicut, Kerala, 673601, India.

Division of Biochemistry and Molecular Biology, Department of Zoology, University of Calicut, Malappuram, Kerala, 673635, India.

出版信息

Sci Rep. 2025 Jul 1;15(1):21762. doi: 10.1038/s41598-025-95078-8.

Abstract

4-Aminocoumarins are significant in organic synthesis as key building blocks for various heterocyclic structures with pharmacological importance. This study focuses on synthesizing phenyliodonium derivatives of 4-aminocoumarins (T1-T6) and evaluating their broad-spectrum biological properties, including antibacterial, antifungal, antiviral, antioxidant, cytotoxicity, and wound-healing properties. The compounds synthesized were structurally confirmed through UV-Vis, GC-MS, H-NMR, C-NMR, FT-IR, melting point, and CHNS analysis. The in vitro antibacterial and antifungal activities of these compounds were assessed against eight bacterial strains and five plant fungal pathogens. The antiviral property was evaluated by measuring the reduction in cytopathic effects of Dengue virus type-2 in BHK-21 cells. Cytotoxicity testing on human epidermal keratinocyte cells using the MTT assay at concentrations ranging from 1 to 100 µg/mL revealed that none of the compounds exhibited significant cytotoxic effects. Additionally, ADME/Toxicity, molecular docking, antioxidant, and wound-healing studies were examined, further supporting the therapeutic potential of these compounds. Most of the synthesized phenyliodonium derivatives demonstrated broad-spectrum antibacterial and antifungal activities. Among them, Compound T6 exhibited the most potent antimicrobial activity, as indicated by its MIC₉₀ and MBC values, demonstrating superior efficacy compared to ciprofloxacin. The antiviral test against Dengue virus type-2 showed minimal effects with a cytopathic effect reduction of 10-13% at non-toxic concentrations. These compounds exhibited broad-spectrum antimicrobial activity coupled with minimal cytotoxicity, highlighting their potential as promising candidates for developing novel therapeutic agents.

摘要

4-氨基香豆素在有机合成中具有重要意义,是各种具有药理学重要性的杂环结构的关键构建单元。本研究重点合成4-氨基香豆素的苯基碘鎓衍生物(T1-T6),并评估其广谱生物学特性,包括抗菌、抗真菌、抗病毒、抗氧化、细胞毒性和伤口愈合特性。通过紫外可见光谱、气相色谱-质谱联用、氢核磁共振、碳核磁共振、傅里叶变换红外光谱、熔点测定和元素分析对合成的化合物进行结构确认。评估了这些化合物对八种细菌菌株和五种植物真菌病原体的体外抗菌和抗真菌活性。通过测量登革热2型病毒在BHK-21细胞中的细胞病变效应的降低来评估抗病毒特性。使用MTT法在1至100μg/mL的浓度范围内对人表皮角质形成细胞进行细胞毒性测试,结果表明这些化合物均未表现出明显的细胞毒性作用。此外,还进行了药物代谢动力学/毒性、分子对接、抗氧化和伤口愈合研究,进一步支持了这些化合物的治疗潜力。大多数合成的苯基碘鎓衍生物表现出广谱抗菌和抗真菌活性。其中,化合物T6表现出最有效的抗菌活性,其MIC₉₀和MBC值表明其疗效优于环丙沙星。对登革热2型病毒的抗病毒测试显示,在无毒浓度下,细胞病变效应降低10-13%,效果最小。这些化合物表现出广谱抗菌活性,同时细胞毒性最小,突出了它们作为开发新型治疗药物的有前途候选物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74b4/12218390/c753ebc3009b/41598_2025_95078_Fig1_HTML.jpg

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