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

Authors

Mohamed Fares, University of Wollongong, Egyptian Russian UniversityFollow
Soha Abd El Hadi, Egyptian Russian University
Radwa A. Eladwy, Egyptian Russian University
Aly Shoun, Badr University in Cairo
Marwa Abdel-Aziz, Al-Azhar University
Wagdy M. Eldehna, Kafrelsheikh University
Hatem A. Abdel-Aziz, National Research Center, Egypt
Paul A. Keller, University of WollongongFollow

RIS ID

127499

Publication Details

Fares, M., Abd El Hadi, S. R., Eladwy, R. A., Shoun, A. A., Abdel-Aziz, M. M., Eldehna, W. M., Abdel-Aziz, H. A. & Keller, P. A. (2018). An improved synthesis of pyrido[2,3-: d] pyrimidin-4(1 H)-ones and their antimicrobial activity. Organic and Biomolecular Chemistry, 16 (18), 3389-3395.

Abstract

The screening of a small library of diverse chemical structures resulted in the identification of 2-thioxodihydropyrido[2,3-d]pyrimidine 10a as having broad spectrum antibacterial activity (MIC 0.49-3.9 μg mL^-1), and reasonable antifungal activity (MIC 31.25 μg 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, I₂ (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 μg 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 1.95-15.63 μg mL^-1.