PDF(Pubmed)
Abstract：
The thiosemicarbazones and their derivatives have been recognized as antimicrobial agents against human pathogenic bacteria and fungi. Regarding these prospective, this study was designed to address the new antimicrobial agents from thiosemicarbazones and their derivatives. These derivatives were synthesized by multi-step synthesis methods, such as alkylation, acidification, esterification, and formed the 4-(4\'-alkoxybenzoyloxy) thiosemicarbazones and its derivatives (THS1, THS2, THS3, THS4, and THS5). Afterward the synthesis, compounds were characterized by 1H NMR, FTIR spectra, and melting point. Later, the computational tools were applied to evaluate the drug likeness properties, bioavailability score, Lipinski rule, absorption, distribution, metabolism, excretion, and toxicity (ADMET). Secondly, the quantum calculations, for instance HOMO, LUMO and chemical descriptors, were calculated by the density functional theory (DFT). Finally, the molecular docking was performed against seven human pathogenic bacteria, black fungus (Rhizomucor mieh, Mucor lusitanicus, Mycolicibacterium smegmatis) and white fungus strains (Candida Auris, Aspergillus luchuensis, Candida albicans). To check and validate of molecular docking procedure and stability of docked complex for ligand and protein, the molecular dynamic was performed of docked complex. From the docking score with calculating the binding affinity, these derivatives could show a higher affinity than standard drug against all pathogens. From the computational details, it could be decided to do in-vitro test as antimicrobial activity against Staphylococcus aurious, Staphylococcus homonis, Salmonella typhi, and Shigella flexneria. The obtained result of antibacterial activity compared to standard drugs, and it was found that the synthesized compounds were almost same value of standard drug. Finally, it could be said from the in-vitro and in-silico study that the thiosemicarbazones derivatives are good antimicrobial agents.
摘要：
氨基硫脲及其衍生物已被认为是针对人类病原细菌和真菌的抗微生物剂。关于这些前景，本研究的目的是研究来自缩氨基硫脲及其衍生物的新型抗菌药物。这些衍生物是通过多步合成方法合成的，如烷基化，酸化,酯化,并形成4-（4'-烷氧基苯甲酰氧基）氨基硫脲及其衍生物（THS1，THS2，THS3，THS4和THS5）。之后的合成，化合物通过1HNMR表征，FTIR光谱,和熔点。稍后，将计算工具应用于评估药物相似性特性，生物利用度评分，利平斯基统治,吸收，分布，新陈代谢，排泄,和毒性（ADMET）。其次,量子计算，比如HOMO,LUMO和化学描述符，通过密度泛函理论(DFT)计算。最后,对七种人类致病菌进行了分子对接，黑木耳（Rhizomucormieh，Mucorlusitanicus,耻垢分枝杆菌）和白真菌菌株（念珠菌，鲁川曲霉,白色念珠菌）。为了检查和验证配体和蛋白质对接复合物的分子对接程序和稳定性，对接复合体的分子动力学。从对接分数和计算结合亲和力，这些衍生物可能比标准药物对所有病原体表现出更高的亲和力。从计算细节来看，可以决定进行体外试验作为对金黄色葡萄球菌的抗菌活性，人葡萄球菌,伤寒沙门氏菌,和弯曲志贺氏菌.与标准药物相比，获得的抗菌活性结果，发现合成的化合物与标准药物的价值几乎相同。最后,从体外和计算机研究可以说，氨基硫脲衍生物是良好的抗菌剂。
