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The Synthesis and Biological Evaluation of 2-(1H-Indol-3-yl)quinazolin-4(3H)-One Derivatives
Molecules ( IF 4.2 ) Pub Date : 2023-07-11 , DOI: 10.3390/molecules28145348 Elena Y Mendogralo 1 , Larisa Y Nesterova 1, 2 , Ekaterina R Nasibullina 1 , Roman O Shcherbakov 1 , Alexander G Tkachenko 1, 2 , Roman Y Sidorov 1, 2 , Maxim A Sukonnikov 3 , Dmitry A Skvortsov 3 , Maxim G Uchuskin 1
Molecules ( IF 4.2 ) Pub Date : 2023-07-11 , DOI: 10.3390/molecules28145348 Elena Y Mendogralo 1 , Larisa Y Nesterova 1, 2 , Ekaterina R Nasibullina 1 , Roman O Shcherbakov 1 , Alexander G Tkachenko 1, 2 , Roman Y Sidorov 1, 2 , Maxim A Sukonnikov 3 , Dmitry A Skvortsov 3 , Maxim G Uchuskin 1
Affiliation
The treatment of many bacterial diseases remains a significant problem due to the increasing antibiotic resistance of their infectious agents. Among others, this is related to Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) and Mycobacterium tuberculosis. In the present article, we report on antibacterial compounds with activity against both S. aureus and MRSA. A straightforward approach to 2-(1H-indol-3-yl)quinazolin-4(3H)-one and their analogues was developed. Their structural and functional relationships were also considered. The antimicrobial activity of the synthesized compounds against Mycobacterium tuberculosis H37Rv, S. aureus ATCC 25923, MRSA ATCC 43300, Candida albicans ATCC 10231, and their role in the inhibition of the biofilm formation of S. aureus were reported. 2-(5-Iodo-1H-indol-3-yl)quinazolin-4(3H)-one (3k) showed a low minimum inhibitory concentration (MIC) of 0.98 μg/mL against MRSA. The synthesized compounds were assessed via molecular docking for their ability to bind long RSH (RelA/SpoT homolog) proteins using mycobacterial and streptococcal (p)ppGpp synthetase structures as models. The cytotoxic activity of some synthesized compounds was studied. Compounds 3c, f, g, k, r, and 3z displayed significant antiproliferative activities against all the cancer cell lines tested. Indolylquinazolinones 3b, 3e, and 3g showed a preferential suppression of the growth of rapidly dividing A549 cells compared to slower growing fibroblasts of non-tumor etiology.
中文翻译：
2-(1H-吲哚-3-基)喹唑啉-4(3H)-1衍生物的合成及生物学评价
由于传染原的抗生素耐药性不断增加，许多细菌性疾病的治疗仍然是一个重大问题。其中，这与金黄色葡萄球菌有关，尤其是耐甲氧西林金黄色葡萄球菌（MRSA）和结核分枝杆菌。在本文中，我们报告了对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌均具有活性的抗菌化合物。开发了一种直接制备 2-(1H-吲哚-3-基)喹唑啉-4(3H)-酮及其类似物的方法。还考虑了它们的结构和功能关系。报道了合成化合物对结核分枝杆菌 H37Rv、金黄色葡萄球菌 ATCC 25923、MRSA ATCC 43300、白色念珠菌 ATCC 10231 的抗菌活性，及其在抑制金黄色葡萄球菌生物膜形成中的作用。2-(5-Iodo-1H-indol-3-yl)quinazolin-4(3H)-one (3k) 对 MRSA 显示出较低的最低抑制浓度 (MIC)，为 0.98 μg/mL。使用分枝杆菌和链球菌 (p)ppGpp 合成酶结构作为模型，通过分子对接评估合成的化合物结合长 RSH (RelA/SpoT 同源物) 蛋白的能力。研究了一些合成化合物的细胞毒活性。化合物 3c、f、g、k、r 和 3z 对所有测试的癌细胞系均表现出显着的抗增殖活性。与非肿瘤病因的生长较慢的成纤维细胞相比，吲哚喹唑啉酮 3b、3e 和 3g 显示出优先抑制快速分裂的 A549 细胞的生长。
更新日期：2023-07-11
中文翻译：
2-(1H-吲哚-3-基)喹唑啉-4(3H)-1衍生物的合成及生物学评价
由于传染原的抗生素耐药性不断增加，许多细菌性疾病的治疗仍然是一个重大问题。其中，这与金黄色葡萄球菌有关，尤其是耐甲氧西林金黄色葡萄球菌（MRSA）和结核分枝杆菌。在本文中，我们报告了对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌均具有活性的抗菌化合物。开发了一种直接制备 2-(1H-吲哚-3-基)喹唑啉-4(3H)-酮及其类似物的方法。还考虑了它们的结构和功能关系。报道了合成化合物对结核分枝杆菌 H37Rv、金黄色葡萄球菌 ATCC 25923、MRSA ATCC 43300、白色念珠菌 ATCC 10231 的抗菌活性，及其在抑制金黄色葡萄球菌生物膜形成中的作用。2-(5-Iodo-1H-indol-3-yl)quinazolin-4(3H)-one (3k) 对 MRSA 显示出较低的最低抑制浓度 (MIC)，为 0.98 μg/mL。使用分枝杆菌和链球菌 (p)ppGpp 合成酶结构作为模型，通过分子对接评估合成的化合物结合长 RSH (RelA/SpoT 同源物) 蛋白的能力。研究了一些合成化合物的细胞毒活性。化合物 3c、f、g、k、r 和 3z 对所有测试的癌细胞系均表现出显着的抗增殖活性。与非肿瘤病因的生长较慢的成纤维细胞相比，吲哚喹唑啉酮 3b、3e 和 3g 显示出优先抑制快速分裂的 A549 细胞的生长。
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