Kasturi Sivaprasad, Surarapu Sujatha, Uppalanchi Srinivas, Anireddy Jaya Shree, Dwivedi Shubham, Anantaraju Hasitha Shilpa, Perumal Yogeeswari, Sigalapalli Dilep Kumar, Babu Bathini Nagendra, Ethiraj Krishna S
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd, Plot. No. 28 A, IDA, Nacharam, Hyderabad 500076, Telangana State, India; Centre for Chemical Sciences & Technology, Institute of Science and Technology, JNTUH, Kukatpally, Hyderabad 500085, Telangana State, India.
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd, Plot. No. 28 A, IDA, Nacharam, Hyderabad 500076, Telangana State, India.
Bioorg Med Chem Lett. 2017 Jun 15;27(12):2818-2823. doi: 10.1016/j.bmcl.2017.04.078. Epub 2017 May 2.
A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides. Among all the compounds, 5o/6o having polar -NH group, 10f/11f having polar -OH group on phenyl ring displayed 3-4-fold more potent than the standard drugs. Acarbose, Voglibose and Miglitol were used as standard references. The promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified. Molecular docking simulations were done for compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.
设计并合成了一系列新型的去乙酰基肌氨酸酰胺A和B衍生物，即3,4-二羟基吡咯烷的酰胺和磺酰胺作为α-葡萄糖苷酶抑制剂。针对α-葡萄糖苷酶的生物筛选试验表明，其中一些化合物对α-葡萄糖苷酶具有阳性抑制活性。饱和脂肪族酰胺比烯属酰胺更有效。在所有化合物中，具有极性-NH基团的5o/6o、在苯环上具有极性-OH基团的10f/11f的活性比标准药物高3-4倍。阿卡波糖、伏格列波糖和米格列醇用作标准对照。已鉴定出有前景的化合物6i、5o、6o、10a、11a、10f和11f。对化合物进行了分子对接模拟，以确定导致α-葡萄糖苷酶抑制活性的重要结合模式。
