Molecular modeling studies, in vitro antioxidant and antimicrobial assay and BSA affinity of novel benzyl-amine derived scaffolds as CYP51B inhibitors.

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED
Jovana S Marjanović, Jovana D Matić, Žiko Milanović, Vera M Divac, Marijana M Kosanić, Miloš R Petković, Marina D Kostić
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Abstract

New scaffolds derived from benzylamine were prepared, characterized, and tested for their antimicrobial, antioxidant activities and binding interactions with BSA. Structure-activity relationship analysis revealed that compounds incorporating both benzylamine and quinoline or pyridine moieties (specifically 3a and 3d) demonstrated potent antifungal activity, surpassing that of the standard drug Ketoconazole against Penicillium italicum. Molecular docking studies confirmed significant inhibitory activity against the CYP51B enzyme-an essential component of fungal cell walls. In addition, compounds 3h, 3d and 3b displayed promising DPPH radical scavenging activity, indicating its strong potential as an antioxidant source. Thermodynamic parameters of standard antiradical mechanisms confirmed antiradical capacity expressed via formal hydrogen atom transfer (FHT). The results of spectrofluorometric assays and molecular docking studies on the affinity of the tested compounds for the BSA enzyme confirmed that all compounds show significant binding affinity for active site III, with compound 3d demonstrating the highest binding affinity. Key pharmacokinetic parameters were assessed using ADMET analysis, ensuring the viability of these compounds for potential therapeutic applications.

新型苯胺基支架作为CYP51B抑制剂的分子模型研究、体外抗氧化和抗菌实验以及BSA亲和力。
制备了新型的苯胺支架,对其进行了表征,并对其抗菌、抗氧化活性和与牛血清白蛋白的结合相互作用进行了测试。构效关系分析显示,含有苄胺和喹啉或吡啶部分的化合物(特别是3a和3d)显示出有效的抗真菌活性,超过了标准药物酮康唑对意大利青霉的抗真菌活性。分子对接研究证实了对真菌细胞壁必需成分CYP51B酶的显著抑制活性。此外,化合物3h、3d和3b显示出良好的DPPH自由基清除活性,表明其具有很强的抗氧化潜力。标准抗自由基机制的热力学参数证实了形式氢原子转移(FHT)表达的抗自由基能力。荧光光谱分析和分子对接研究结果证实,所有化合物都对活性位点III具有显著的结合亲和力,其中化合物3d的结合亲和力最高。使用ADMET分析评估关键药代动力学参数,确保这些化合物具有潜在的治疗应用的可行性。
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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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