Abstract

We have developed a simple and convenient method for the synthesis of substituted-aryllidine-2,2-dimethyl-7-thioxo/oxo-4H-[1,3]dioxino[4,5-d]pyrimidine derivatives (4a-g) via one-pot Biginelli reaction of Meldrum’s acid (1), indole-3-carbaldehyde/thiophene-2-carbaldehyde/2-chloro-quinoline-3-carbaldehyde (2) and amines (3) in aqueous ethanol in the presence of a catalytic amount of CAN. The obtained pyrimidine hybrids were screened for their antimycobacterial activity against Mycobacterium tuberculi H₃₇RV strain. The antimycobacterial results showed that compounds 4a and 4b exhibited excellent activity with MIC value of 1.6 µg/mL, four-fold greater than the standard streptomycin (6.24 µg/mL), while compounds (4c-g) showed lower efficacy. To study the interaction between the synthesized compounds and receptor, the compounds 4a, 4b, 4c, and 4d were studied for molecular docking on the enzyme enoyl-acyl carrier protein reductase (enoyl-ACP reductase) and the compounds 4a and 4b have emerged as active antitubercular agents with least binding energy –9.4 kcal/mol and −9.3 kcal/mol respectively.

摘要

我们开发了一种简单方便的方法来合成取代的芳基烷-2,2-二甲基-7-硫代/氧代-4H-[1,3]二恶英[4,5-d]嘧啶衍生物( 4a-g )通过 Meldrum 酸 ( 1 )、吲哚-3-甲醛/噻吩-2-甲醛/2-氯喹啉-3-甲醛 ( 2 ) 和胺类 ( 3 ) 在乙醇水溶液中的一锅 Biginelli 反应。CAN的催化量。筛选获得的嘧啶杂合体对结核分枝杆菌H ₃₇ RV 菌株的抗分枝杆菌活性。抗分枝杆菌结果表明，化合物4a和4b表现出优异的活性，MIC 值为 1.6 µg/mL，是标准链霉素 (6.24 µg/mL) 的四倍，而化合物 ( 4c-g ) 的功效较低。为研究合成的化合物与受体之间的相互作用，研究了化合物4a、4b、4c和4d与酶烯酰-酰基载体蛋白还原酶 (enoyl-ACP reductase) 的分子对接，化合物4a和4b已出现为结合能最低的活性抗结核药物分别为 –9.4 kcal/mol 和 -9.3 kcal/mol。