Department of Pharmaceutical Chemistry, School of Medical and Allied Sciences, K.R. Mangalam University, Sohna Road, Sohna Rural, Haryana 122103, India.
Department of Pharmaceutical Chemistry, GITAM Institute of Pharmacy, Rushikonda, GITAM (Deemed to be University), Visakhapatnam-530045, Andhra Pradesh, India.
Curr HIV Res. 2022;20(3):255-271. doi: 10.2174/1570162X20666220512163049.
The necessity for newer anti-HIV and anti-tubercular medications has arisen as a result of the prevalence of opportunistic infections caused by HIV (human immunodeficiency virus).
A series of ten new hydrazono 1,3-thiazolidin-4-one derivatives were synthesized in one-pot and evaluated for anti-HIV and anti-tubercular activities. Molecular Docking was accomplished with HIV-1 reverse transcriptase protein (PDB ID: 1REV) and Mycobacterium Tuberculosis (M. tuberculosis) H37Rv protein (PDB ID: 2YES) receptors along with drug-likeness and ADMET properties.
One-pot synthesis of hydrazono 1,3-thiazolidin-4-one derivatives was carried out by ketones, thiosemicarbazide and ethylchloroacetate with the catalyst of anhydrous sodium acetate. All the synthesized compounds were characterized and evaluated for their in-vitro anti-HIV and also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis HRv. In-silico predicted physicochemical parameters were done by MedChem DesignerTM software version 5.5 and ADMET parameters by pkCSM online tool. Furthermore, molecular docking was performed with pyrx 0.8 by autodock vina software.
All the synthesized compounds were characterized and evaluated for their in-vitro anti- HIV activity for inhibition of syncytia formation, which shows KTE1 with EC 47.95 μM and Selectivity Index (SI) of >4.17 and for inhibition of p24 antigen production EC was found to be 80.02 μM and SI of >2.49. The compounds were also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis HRv, in which KTE1 MIC values of 12.5μg/ml with SI of >4.0 and cytotoxicity against Vero cell lines. In-silico predicted physicochemical parameters for synthesized compounds which were found to be drug-like. Furthermore, docking has shown a good dock score and binding energy with anti-HIV and anti-tubercular receptors.
From the novel synthesized molecules, none of the molecule is as effective as standards for anti-HIV and anti-tubercular drugs and hence can be further explored for its potential activities. Furthermore, derivatization was made to achieve more potent compounds for anti-HIV and anti-tubercular drugs.
由于 HIV（人类免疫缺陷病毒）引起的机会性感染的流行，需要新型抗 HIV 和抗结核药物。
一锅法合成了一系列十个新的腙 1,3-噻唑烷-4-酮衍生物，并对其抗 HIV 和抗结核活性进行了评价。利用 HIV-1 逆转录酶蛋白（PDB ID：1REV）和结核分枝杆菌（M. tuberculosis）H37Rv 蛋白（PDB ID：2YES）受体进行分子对接，并对药物相似性和 ADMET 性质进行了研究。
以酮、硫代氨基脲和氯乙酸乙酯为原料，无水醋酸钠为催化剂，一锅法合成腙 1,3-噻唑烷-4-酮衍生物。所有合成的化合物均进行了表征，并对其体外抗 HIV 活性进行了评价，同时对其体外抗结核活性进行了评价结核分枝杆菌 HRv。利用 MedChem DesignerTM 软件版本 5.5 预测了化合物的理化参数，并利用 pkCSM 在线工具预测了 ADMET 参数。此外，利用 autodock vina 软件的 pyrx 0.8 进行了分子对接。
所有合成的化合物均进行了表征，并对其体外抗 HIV 活性进行了评价，以抑制合胞体形成，其中 KTE1 的 EC 47.95 μM 和选择性指数（SI）>4.17，抑制 p24 抗原产生的 EC 为 80.02 μM，SI>2.49。这些化合物还对结核分枝杆菌 HRv 的体外抗结核活性进行了评价，其中 KTE1 的 MIC 值为 12.5μg/ml，SI>4.0，对 Vero 细胞系的细胞毒性。预测了合成化合物的理化参数，发现它们具有类药性。此外，对接显示出与抗 HIV 和抗结核受体良好的对接评分和结合能。
从新合成的分子中，没有一个分子像抗 HIV 和抗结核药物的标准一样有效，因此可以进一步探索其潜在的活性。此外，还进行了衍生化，以获得更有效的抗 HIV 和抗结核药物。
