Anti-diabetic potential, crystal structure, molecular docking, DFT, and optical-electrochemical studies of new dimethyl and diethyl carbamoyl-N, N′-disubstituted based thioureas
Anti-diabetic potential, crystal structure, molecular docking, DFT, and optical-electrochemical studies of new dimethyl and diethyl carbamoyl-N, N′-disubstituted based thioureas
复制标题
DOI：
10.1016/j.molstruc.2021.132207
复制
发表时间：
2022-01-02
影响因子：
3.8
通讯作者：
Murtaza, Iram
中科院分区：
文献类型：
--
作者：
Khan, Mehmand;Patujo, Jahangeer;Murtaza, Iram
采用多组分法合成了四种新的含二甲基和二乙基氨基甲酰基骨架的硫脲衍生物。α-淀粉酶与硫脲的对接分析表明，3-（3-二甲基氨基甲酰基）硫脲基）苯甲酸可以有效地结合到疏水腔中，并与人胰腺α-淀粉酶的HISA：103、ASP A：326、ARGA：407、ARGA：411有效地形成氢键。抗糖尿病研究显示，化合物DM 3A（IC 50 = 19.26 +/- 0.23）随后是3-（3-（二乙基氨基甲酰基）硫脲基）苯甲酸（IC 50 = 21.89 +/- 0.06）对α-淀粉酶和α-葡糖苷酶更有效，与标准药物阿卡波糖相当。DM 3A具有最好的抗氧化能力（DPPH IC_（50）= 7.97 ± 0.23 μ g/ml，TAC IC_（50）= 8.19 ± 0.64 μ g/ml，总还原力IC_（50）= 8.19 ± 0.23 μ g/ml），但溶血活性不明显。此外，DFT，分子静电势和光学电化学研究也进行了支持在硅片和体外生物筛选结果。最后，药理学特征显示DM 3A可能是可能的先导化合物。此外，建议进行体内研究，以充分确定这些新合成的硫脲衍生物的生物光谱。(c)2021 Elsevier B.V.版权所有。
Four new thiourea derivatives containing dimethyl and diethyl carbamoyl scaffolds have been synthesized by multicomponent methodology. Docking analysis of alpha-amylase with thioureas showed that the 3-(3-dimethyl carbamoyl) thioureido) benzoic acid can effectively bind to the hydrophobic cavity and form hydrogen bonding effectively with the HIS A:103, ASP A:326, ARG A:407, ARG A:411 of human pancreatic alpha-amylase. The anti-diabetic studies revealed that compound DM3A (IC50 = 19.26 +/- 0.23) followed by 3-(3-(diethyl carbamoyl) thioureido) benzoic acid (IC50 = 21.89 +/- 0.06) were more potent against alpha-amylase and alpha-glucosidase, comparable to that of standard drug acarbose. DM3A displayed best antioxidant potential (DPPH IC50 = 7.97 +/- 0.23 mu g/ml, TAC IC50 = 8.19 +/- 0.64 mu g/ml, Total reducig power IC50 = 8.19 +/- 0.23 mu g/ml) but insignificant hemolytic activity. Further, DFT, molecular electrostatic potential and optical-electrochemical studies were also performed to support the in-silico and in-vitro biological screening results. Finally, the pharmacological profile revealed that DM3A might be possible lead compound. Further, in-vivo research is recommended to fully determine the biological spectrum of these newly synthesized thiourea derivatives. (c) 2021ElsevierB.V. Allrightsreserved.