A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a–5v) has been synthesized and confirmed by physicochemical(Rf, melting point) and spectral means (IR, 1HNMR, 13CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH3-5-NO2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH3) group and electron withdrawing (NO2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski’s rule of 5 and Veber’s rule.

中文翻译：

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作为抗糖尿病药的2-氯-5-[（4-氯苯基）氨磺酰基] -N-（烷基/芳基）-4-硝基苯甲酰胺衍生物的合成，分子对接和分子动力学模拟研究。

合成了一系列2-氯-5-[（4-氯苯基）氨磺酰基] -N-（烷基/芳基）-4-硝基苯甲酰胺衍生物（5a-5v），并通过理化（Rf，熔点）和光谱证实平均值（IR，1HNMR，13CNMR）。对α-葡萄糖苷酶的体外抗糖尿病研究结果表明，发现在苯环上带有2-CH3-5-NO2取代基的化合物5o是对这两种酶活性最高的化合物。苯环上的给电子基团（CH3）和吸电子基团（NO2）非常有利于抑制这些酶的活性。对接模拟研究表明，这些合成的化合物显示出与活性位点残基的氢键，静电和疏水相互作用。这些化合物的结构活性关系研究也得到了分子模型研究的证实。为了验证其最强活性化合物的α-葡萄糖苷酶和α-淀粉酶抑制潜力，已经进行了分子动力学模拟。配体蛋白复合物的RMSD分析表明，最强活性化合物5o在靶蛋白结合位点的稳定性。在计算机模拟中，ADMET结果表明，所合成的化合物满足Lipinski的5规则和Veber的规则，其毒性，可溶性和吸收特性均可以忽略不计。配体蛋白复合物的RMSD分析表明，最活跃的化合物5o在目标蛋白的结合位点具有稳定性。在计算机模拟中，ADMET结果表明，所合成的化合物满足Lipinski的5规则和Veber的规则，其毒性，可溶性和吸收特性均可以忽略不计。配体蛋白复合物的RMSD分析表明，最活跃的化合物5o在目标蛋白的结合位点具有稳定性。在计算机模拟中，ADMET的结果表明，所合成的化合物满足Lipinski规则5和Veber规则，因此其毒性，溶解度和吸收特性均可以忽略不计。