Simakov Sergei, Kartsev Victor, Petrou Anthi, Nicolaou Ioannis, Geronikaki Athina, Ivanov Marija, Kostic Marina, Glamočlija Jasmina, Soković Marina, Talea Despoina, Vizirianakis Ioannis S
Laboratory of General Chemistry, Chemistry Department, Belgorod State University, 308015 Belgorod, Belgorod Oblast, Russia.
InterBioScreen, 142432 Chernogolovka, Moscow Region, Russia.
Pharmaceuticals (Basel). 2021 Oct 28;14(11):1096. doi: 10.3390/ph14111096.
This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (-) bacteria revealed that the MIC of indole derivatives is in the range of 0.06-1.88 mg/mL, while among fourteen methylindole derivatives, only six were active, with an MIC in the range of of 0.47-1.88 mg/mL. appeared to be the most resistant strain, while Typhimurium was the most sensitive. Compound was the most promising, with an MIC in the range of 0.06-0.12 mg/mL, followed by and . An evaluation of these three compounds against resistant strains, namely MRSA and , revealed that they were more potent against MRSA than ampicillin. Furthermore, compounds and were superior inhibitors of biofilm formation, compared to ampicillin and streptomycin, in terms Compounds , , and interact with streptomycin in additive manner. The antifungal activity of some compounds exceeded or was equipotent to those of the reference antifungal agents bifonazole and ketoconazole. The most potent antifungal agent was found to be compound . Drug likeness scores of compounds was in a range of -0.63 to 0.29, which is moderate to good. According to docking studies, MurB inhibition is probably responsible for the antibacterial activity of compounds, whereas CYP51 inhibition was implicated in antifungal activity. Compounds appeared to be non-toxic, according to the cytotoxicity assessment in MRC-5 cells.
本手稿涉及29种4-(吲哚-3-基)噻唑-2-胺和4-(吲哚-3-基)噻唑酰胺的合成及其抗菌活性的计算和实验评估。对革兰氏阳性菌和革兰氏阴性菌的抗菌活性评估表明，吲哚衍生物的最低抑菌浓度（MIC）在0.06 - 1.88mg/mL范围内，而在14种甲基吲哚衍生物中，只有6种具有活性，MIC在0.47 - 1.88mg/mL范围内。 似乎是最具抗性的菌株，而鼠伤寒沙门氏菌是最敏感的。化合物 最具前景，MIC在0.06 - 0.12mg/mL范围内，其次是 和 。对这三种化合物针对耐药菌株，即耐甲氧西林金黄色葡萄球菌（MRSA） 和 的评估表明，它们对MRSA的效力比氨苄西林更强。此外，与氨苄西林和链霉素相比，化合物 和 是更优异的生物膜形成抑制剂。化合物 、 和 与链霉素以加和方式相互作用。一些化合物的抗真菌活性超过或等同于参考抗真菌剂联苯苄唑和酮康唑。发现最有效的抗真菌剂是化合物 。化合物的类药性质评分在 -0.63至0.29范围内，属于中等至良好。根据对接研究，MurB抑制可能是化合物抗菌活性的原因，而CYP51抑制与抗真菌活性有关。根据在MRC - 5细胞中的细胞毒性评估，化合物似乎无毒。
