以生态意识合成新型 1,2,4-三唑并[1,5-a]嘧啶衍生物作为强效抗微生物剂,并利用印度醋栗(Phyllanthus emblica)果实提取物对 HEK-293 细胞系的细胞活力和细胞毒性进行比较研究。

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-11-06 DOI:10.1016/j.bioorg.2024.107936
Bhaktiben R Bhatt, Kamalkishor Pandey, Tarosh Patel, Anupama Modi, Chandani Halpani, Vaibhav D Bhatt, Bharat C Dixit
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引用次数: 0

摘要

抗菌药耐药性(AMR)是一项紧迫的全球健康挑战,需要寻找新型抗菌剂和合成方法。本研究考察了 25 种新型 1,2,4-三唑并[1,5-a]嘧啶衍生物的合成和抗菌功效,这些衍生物由富含有机酸和多酚化合物的阿姆拉(Phyllanthus emblica)果汁催化,因此可作为环境可持续催化剂,符合绿色化学原则。与传统方法相比,该合成方法采用单锅无溶剂工艺,能在更短的时间内获得大量所需的化合物。该化合物针对一系列临床相关微生物进行了全面的抗菌评估,包括暴力铬杆菌、肺炎克雷伯菌、大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌、白色念珠菌、新生隐球菌和黑曲霉。同时,还对 HEK-293 细胞进行了细胞毒性试验,以评估其安全性,结果表明化合物 B-1、B-6、B-7、B-14 和 B-15 在保持低细胞毒性和高细胞活力的同时,还表现出了强大的抗菌活性。这些发现凸显了合成化合物在抗击传染病和应对 AMR 带来的挑战方面的治疗潜力,同时强调了剂量优化在治疗应用中的重要性。这项研究可防治传染病,减轻 AMR 带来的挑战,并为抗菌药物发现领域做出了重大贡献,强调了可持续合成策略与未来制药努力相一致的必要性。我们的研究不仅促进了对这些新型化合物的了解,还支持了目前针对耐药性病原体开发安全有效疗法的工作。
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Eco-conscious synthesis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives as potent Anti-microbial agent and comparative study of cell viability and cytotoxicity in HEK-293 cell line utilizingIndian gooseberry (Phyllanthus emblica) fruit extract.

Antimicrobial resistance (AMR) is a pressing global health challenge that necessitates the search for novel antimicrobial agents and synthetic methodologies. This study investigates the synthesis and antimicrobial efficacy of 25 novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives, catalyzed by Amla (Phyllanthus emblica) fruit juice, which is rich in organic acids and polyphenolic compounds, thus serving as an environmentally sustainable catalyst, in adherence to green chemistry principles. The synthesis is achieved through a one-pot, solvent-free process that yields high quantities of the desired compounds in significantly less time compared to traditional methods. Comprehensive antimicrobial evaluation was conducted against a range of clinically relevant microorganisms, including Chromobacterium violaceum, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Cryptococcus neoformans and Aspergillus niger. Concurrently, cytotoxic assays were performed on HEK-293 cells, to assess safety profiles, revealing that compounds B-1, B-6, B-7, B-14 and B-15 exhibited potent antimicrobial activity while maintaining low cytotoxicity and high cell viability. These findings underscore the therapeutic potential of the synthesized compounds in combatting infectious diseases and addressing the challenges posed by AMR, highlighting the critical importance of dose optimization in therapeutic applications. This study combats contagious diseases, mitigates AMR challenges and contributes significantly to the field of antimicrobial drug discovery, emphasizing the need for sustainable synthetic strategies that align with future pharmaceutical endeavors. Our research not only advances the understanding of these novel compounds but also supports ongoing efforts to develop safe and effective therapies against resistant pathogens.

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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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