An improved synthesis of pyrido[2,3-d]pyrimidin-4(1H)-ones and their antimicrobial activity

作者：Fares Mohamed^*; Abd El Hadi Soha R; Eladwy Radwa A; Shoun Aly A; Abdel Aziz Marwa M; Eldehna Wagdy M; Abdel Aziz Hatem A; Keller Paul A^*

来源：Organic and Biomolecular Chemistry, 2018, 16(18): 3389-3395.

DOI：10.1039/c8ob00627j

The screening of a small library of diverse chemical structures resulted in the identification of 2-thioxodihydro-pyrido[2,3-d]pyrimidine 10a as having broad spectrum antibacterial activity (MIC 0.49-3.9 mu g mL(-1)), and reasonable antifungal activity (MIC 31.25 mu g mL(-1)). An expeditious synthesis of 10a was optimized by varying solvents, catalysts and the use of microwave irradiation with the best conditions using DMF as a solvent, I-2 (10 mol%) and a 30 minutes reaction time compared to 15 h for classic conventional heating. The pharmacokinetic properties and calculation of drug likeness of 10a suggested good traditional drug-like properties and led to the synthesis of a small library with seven compounds 10a and 10d-i showing broad antimicrobial activity (MIC = 0.49-7.81 mu g mL(-1)) and selectivity indices of more than 5.6 against the normal colon cell line (CCD-33Co). The antifungal activity of compounds 10d-i was moderate to strong with MIC values of L95-15.63 mu g mL(-1).

• 出版日期2018-5-14