Bahare Radhe Shyam, Ganguly Swastika, Choowongkomon Kiattawee, Seetaha Supaporn
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India.
Daru. 2015 Jan 24;23(1):6. doi: 10.1186/s40199-014-0086-1.
Structural modifications of thiazolidinediones at 3rd and 5th position have exhibited significant biological activities. In view of the facts, and based on in silico studies carried out on thiazolidine-2,4-diones as HIV-1- RT inhibitors, a novel series of 2,4-thiazolidinedione analogs have been designed and synthesized.
Title compounds were prepared by the reported method. Conformations of the structures were assigned on the basis of results of different spectral data. The assay of HIV-1 RT was done as reported by Silprasit et al. Antimicrobial activity was determined by two fold serial dilution method. Docking study was performed for the highest active compounds by using Glide 5.0.
The newly synthesized compounds were evaluated for their HIV-1 RT inhibitory activity. Among the synthesized compounds, compound 24 showed significant HIV-1 RT inhibitory activity with 73% of inhibition with an IC50 value of 1.31 μM. Compound 10 showed highest activity against all the bacterial strains.A molecular modeling study was carried out in order to investigate the possible interactions of the highest active compounds 24, 10 and 4 with the non nucleoside inhibitory binding pocket(NNIBP) of RT, active site of GlcN-6-P synthase and cytochrome P450 14-α-sterol demethylase from Candida albicans (Candida P450DM) as the target receptors respectively using the Extra Precision (XP) mode of Glide software.
A series of novel substituted 2-(5-benzylidene-2,4-dioxothiazolidin-3-yl)-N-(phenyl)propanamides (4-31) have been synthesized and evaluated for their HIV-1 RT inhibitory activity, antibacterial and antifungal activities. Some of the compounds have shown significant activity. Molecular docking studies showed very good interaction.
噻唑烷二酮类化合物在第3位和第5位的结构修饰已显示出显著的生物活性。鉴于这些事实，并基于对噻唑烷-2,4-二酮作为HIV-1逆转录酶抑制剂进行的计算机模拟研究，设计并合成了一系列新型的2,4-噻唑烷二酮类似物。
通过报道的方法制备目标化合物。根据不同光谱数据的结果确定结构的构象。HIV-1逆转录酶的测定按照Silprasit等人报道的方法进行。抗菌活性通过两倍系列稀释法测定。使用Glide 5.0对活性最高的化合物进行对接研究。
对新合成的化合物进行了HIV-1逆转录酶抑制活性评估。在合成的化合物中，化合物24显示出显著的HIV-1逆转录酶抑制活性，抑制率为73%，IC50值为1.31μM。化合物10对所有细菌菌株显示出最高活性。进行了分子模拟研究，以分别使用Glide软件的超精确（XP）模式研究活性最高的化合物24、10和4与逆转录酶的非核苷抑制结合口袋（NNIBP）、葡糖胺-6-磷酸合酶的活性位点以及白色念珠菌的细胞色素P450 14-α-甾醇脱甲基酶（念珠菌P450DM）作为目标受体的可能相互作用。
合成了一系列新型取代的2-(5-亚苄基-2,4-二氧代噻唑烷-3-基)-N-(苯基)丙酰胺（4-31），并评估了它们的HIV-1逆转录酶抑制活性、抗菌和抗真菌活性。一些化合物显示出显著活性。分子对接研究显示出很好的相互作用。
