Jovana S Marjanović, Nevena Petrović, Marijana Kosanić, Jelena Košarić, Ana Mirić, Nevena Milivojević, Marina D Kostić, Vera M Divac
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引用次数: 0
摘要
在有机支架中引入吲哚类药物结构可以产生有趣的药理特性,受此启发,我们合成了一系列新型色胺衍生希夫碱。色胺被用作吲哚模式的来源,同时也是生物胺的一个例子,通过化学转化可以得到具有显著生物活性的化合物。针对一系列细菌和真菌菌株的抗菌活性以及细胞毒性活性的研究结果表明,在结构上结合了色胺和对硝基芳基模式的希夫碱 TSB4 在低浓度下比标准药物氟康唑具有更好的抗真菌活性,而由色胺和喹啉分子组成分子支架的化合物 TSB6 对 HCT-116 细胞系具有一定的细胞毒性作用,对健康的成纤维细胞 MRC-5 具有很强的选择性。为了更好地了解这两种化合物的药代动力学并确定其与 DNA 分子的结合模式,我们对这两种化合物进行了额外的 ADME 分析和 DNA 相互作用分析。结果表明,所研究的化合物与 CT-DNA 有很强的结合力,而 ADME 筛选表明,所选化合物具有适合口服生物利用度和药物亲和性的理化特性。
Tryptamine-Derived Schiff Bases: Potent Antimicrobial Agents and Evaluation of Cytotoxicity, ADME and DNA Binding Properties.
Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine-derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p-nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT-116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC-5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT-DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.
期刊介绍:
Chemistry & Biodiversity serves as a high-quality publishing forum covering a wide range of biorelevant topics for a truly international audience. This journal publishes both field-specific and interdisciplinary contributions on all aspects of biologically relevant chemistry research in the form of full-length original papers, short communications, invited reviews, and commentaries. It covers all research fields straddling the border between the chemical and biological sciences, with the ultimate goal of broadening our understanding of how nature works at a molecular level.
Since 2017, Chemistry & Biodiversity is published in an online-only format.