European Journal of Medicinal Chemistry ( IF 6.7 ) Pub Date : 2017-10-26 , DOI: 10.1016/j.ejmech.2017.10.071 Muhammad Taha , Hayat Ullah , Laode Muhammad Ramadhan Al Muqarrabun , Muhammad Naseem Khan , Fazal Rahim , Norizan Ahmat , Muhammad Ali , Shahnaz Perveen
Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1–32 were synthesized and characterized by 1HNMR, 13CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug d-saccharic acid-1,4-lactone (IC50 value 48.30 ± 1.20 μM). Derivatives 1–32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug d-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors.
中文翻译:
双吲哚甲烷甲烷作为新型潜在的β-葡萄糖醛酸苷酶抑制剂的合成及其分子对接研究
三十二(32)双-indolylmethane -腙杂交1 - 32被合成和表征通过1 HNMR,13 CNNMR和HREI-MS。在体外评估所有化合物的β-葡萄糖醛酸苷酶抑制潜力。所有类似物表现出不同程度的β葡萄糖醛酸酶抑制潜力范围从0.10±0.01至48.50±1.10 μ当与标准药物相比中号d -saccharic酸-1,4-内酯(IC 50值48.30±1.20 μ M)。导数1–32显示出最高的β-葡糖醛酸糖苷酶的抑制潜力比标准药物d-蔗糖-1,4-内酯要好很多倍。进一步的分子对接研究验证了实验结果。有人提出双吲哚甲烷可能与位于β-葡萄糖醛酸苷酶的活性位点内的一些氨基酸残基相互作用。这项研究最终确定了新型的有效β-葡萄糖醛酸苷酶抑制剂。