N SILICO PHARMACOPHORE SCREENING OF ANTI - CANCER DRUG AGAINST LEPROSY CAUSING PROTEIN SHMT

Leprosy and its interaction with man is one of suffering and misunderstanding. The newest research suggests that at least as early as 4000 B.C. individuals had been infected with Mycobacterium leprae. The disease develops slowly and results in skin lesions and deformities, most often affecting the cooler places on the body such as eyes, nose, earlobes, hands, feet, and testicles. The skin lesions and deformities can be very disfiguring and are the reason that infected individuals historically were considered outcasts in many cultures. The protein Serine hydroxyl-methyl-transferase (SHMT) play a key role in cell physiology as it participate in the different inter conversion pathway of folate coenzymes. Therefore,present work demonstrates to insilico pharmacophore screening, homology modeling and its validation, anticancer drug interaction against Leprosy causing Protein SHMT. The selected compounds were further analyzed and refined using drug - like filters and ADMET analysis. Finally, 25 hits with different scaffolds were picked out for docking studies. These seven hits were predicted to have high inhibitory activity and good ADMET properties; they may act as novel leads for SHMT inhibit ors designing. <strong>Keywords: </strong>Leprosy, Mycobacterium leprae, SHMT

麻风病及其与人类的纠葛，始终伴随着苦难与误解。最新研究表明，早在公元前4000年就已有个体感染麻风分枝杆菌（Mycobacterium leprae）。该病病程进展缓慢，会引发皮肤损伤与畸形，最常累及机体温度较低的部位，如眼部、鼻腔、耳垂、手部、足部及睾丸。皮肤损伤与畸形可造成严重的容貌损毁，这也是历史上诸多文化中将感染者视为弃民的缘由。丝氨酸羟甲基转移酶（Serine hydroxyl-methyl-transferase，SHMT）在细胞生理学中发挥关键作用，因其参与叶酸辅酶的各类相互转化通路。因此，本研究针对麻风致病蛋白SHMT开展了计算机辅助药效团筛选、同源建模及其验证、抗肿瘤药物相互作用分析。所筛选得到的化合物经类药过滤与ADMET分析后，进一步完成分析与优化。最终，选取25种具有不同骨架结构的命中化合物进行分子对接研究。经预测，其中7种命中化合物具有较高的抑制活性与优良的ADMET特性，可作为SHMT抑制剂研发的新型先导化合物。关键词：麻风病、麻风分枝杆菌、SHMT