Design, synthesis, characterization, molecular docking studies and biological evaluation of 5, 6, 7, 8-tetrahydropyrido[3,4-d]pyrimidine derivatives as antimicrobial agents

New tetrahydropyrido[3,4-d]pyrimidine derivatives (10a-l) have been facilely synthesized through a series of deprotection, N-substitution and Suzuki coupling reactions. The structure of new compounds was analyzed by interpretations of FTIR, ¹HNMR , ¹³CNMR , and Mass spectral data. The title compounds were screened for their in vitro antimicrobial activity against four bacterial strains: Staphylococcus aureus and Bacillus subtilis as gram-positive bacteria, and Escherichia coli and Pseudomonas aeruginosa as gram-negative bacteria and two fungal strains, namely Candida albicans and Aspergillus niger. Trifluoromethyl substituted analogues 10j and 10k showed promising antibacterial activity compared to Amoxicillin, also p‑hydroxy substituted analogue 10i displayed potent antifungal activity in comparison to Itraconazole. The molecular docking study of 10k against crystal structure of DNA gyrase, scored higher docking score value of -9.4 kca/mL, than Clorobiocin, and envisaged key binding interactions in support to experimental data.