Guda Mallikarjuna R, Zyryanov Grigory V, Dubey Amit, Munagapati Venkata Subbaiah, Wen Jet-Chau
Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B.N. Yeltsin, 28 Mira St., Yekaterinburg 620002, Russia.
Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India.
Pharmaceuticals (Basel). 2023 Aug 15;16(8):1159. doi: 10.3390/ph16081159.
A sequence of novel 1,4-dihydropyridines (DHP) and their hybrids was developed using a multicomponent strategy under environmentally benign conditions. In addition, computational studies were performed, and the ligand-protein interactions calculated in different bacteria and two fungal strains. Para-hydroxy-linked DHP () showed the best binding energies of 3.591, 3.916, 8.499 and 6.895 kcal/mol against various pathogens used and other substances received a good docking score. The pathogen resistance potential of the synthesized targets against four bacteria and two fungi showed that whole DHP substances exhibit different levels of resistance to each microorganism. Gram-positive bacteria, which are highly sensitive to all molecules, and the MTCC-1884-encoded fungus strongly rejected the studied compounds compared to comparator drugs. In particular, the candidate showed remarkable antimicrobial activity, followed by the substances , , , and . Furthermore, MIC and MBC/MFC properties showed that had a minimum bacterial concentration of 12.5 μg/mL against and against two fungal pathogens, with its killing activity being effective even at low concentrations. On the other hand, whole motifs were tested for their cytotoxic activity, revealing that the methoxy and hydroxy-linked compounds () showed greater cytotoxic potency, followed by the two hydroxy linked compounds ( and ). Overall, this synthetic approach used represents a prototype for future nature-favored synthesis methods and these biological results serve as a guide for future therapeutic drug research. However, the computer results play an important role in the further development of biological experiments.
在环境友好的条件下，采用多组分策略开发了一系列新型1,4 - 二氢吡啶（DHP）及其杂化物。此外，还进行了计算研究，并计算了在不同细菌和两种真菌菌株中的配体 - 蛋白质相互作用。对羟基连接的DHP（）对所使用的各种病原体显示出最佳结合能，分别为3.591、3.916、8.499和6.895千卡/摩尔，其他物质也获得了良好的对接分数。合成目标物对四种细菌和两种真菌的抗病原体潜力表明，所有DHP物质对每种微生物都表现出不同程度的抗性。与对照药物相比，对所有分子高度敏感的革兰氏阳性菌以及MTCC - 1884编码的真菌强烈排斥所研究的化合物。特别是，候选物显示出显著的抗菌活性，其次是物质、、、和。此外，MIC和MBC/MFC特性表明，对具有12.5μg/mL的最低细菌浓度，对两种真菌病原体也有此浓度，其杀伤活性即使在低浓度下也有效。另一方面，对所有基序进行了细胞毒性活性测试，结果表明甲氧基和羟基连接的化合物（）显示出更大的细胞毒性效力，其次是两种羟基连接的化合物（和）。总体而言，所采用的这种合成方法代表了未来自然友好型合成方法的原型，这些生物学结果为未来的治疗药物研究提供了指导。然而，计算机结果在生物实验的进一步发展中起着重要作用。
