Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Comb Chem High Throughput Screen. 2020;23(2):126-140. doi: 10.2174/1386207323666200127115238.
The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated.
The preparation of the substituted 5-benzylidene-2-thiazolyimino-4- thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi strains. Minimum inhibitory concentration and minimum bacterial concentration were both determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the title compounds.
PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone hybrids. All tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective molecular target identification and revealed favorable interaction with the target enzymes E. coli MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active compounds was found toxic.
Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and may find a potential therapeutic use to eradicate infectious diseases.
由于与多种药物耐药相关的致病微生物数量不断增加，传染病的治疗仍然是一个具有挑战性的问题。对抗微生物感染的一种有前途的方法是将两种或多种已知的生物活性杂环药效团结合到一个分子平台中。本文合成并评价了新型噻唑-噻唑烷酮杂合体作为潜在抗菌剂的生物活性。
从 2-氨基-5-甲基噻唑啉出发，经三步反应合成了取代的 5-亚苄基-2-噻唑亚氨基-4-噻唑烷酮。所有化合物均经过 PASS 抗菌活性预测以及一系列细菌和真菌菌株的筛选。采用微量稀释法测定最小抑菌浓度和最小细菌浓度。利用 Accelrys Discovery Studio 4.0 客户端进行分子模拟。利用 ToxPredict（OPEN TOX）和 ProTox 预测标题化合物的毒性。
PASS 预测显示设计的噻唑-噻唑烷酮杂合体具有潜在的抗菌特性。所有测试的化合物都能杀死并抑制各种细菌和真菌的生长，其活性均强于商业药物链霉素、氨苄西林、比福莫唑和酮康唑。此外，通过计算机模拟研究了潜在的分子靶标识别，并发现与大肠杆菌 MurB 和烟曲霉 CYP51B 的靶酶有良好的相互作用。毒性预测表明，没有一种活性化合物被认为是有毒的。
取代的 5-亚苄基-2-噻唑亚氨基-4-噻唑烷酮具有显著的抗菌和抗真菌活性，被鉴定为一类新型抗菌药物，可能具有消除传染病的潜在治疗用途。
