Design, synthesis and molecular modeling study of 1,2,4-triazolo[1,5-a] pyrimidines with potential biological activities / Rehab Hamed Abdelaleam ; Supervised Ghaneya Sayed Hassan , Hamdy M. Abdelrahman , Riham François George

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

1,2,4-Triazolo[1,5-a]pyrimidines attract more attention due to their diverse pharmacological activities such as, antibacterial, antifungal, phosphodiesterase inhibition, anti-inflammatory, anticancer and anti-Alzheimer activities. In this work, 1,2,4-triazolo[1,5-a]pyrimidine derivatives were synthesized (8 compounds as key intermediates and 36 as new final compounds). All the newly final compounds were screened for their antibacterial and antifungal activities and their possible cytotoxicity against human embryonic kidney cell line and hemolysis of human red blood cells. The most active compounds were 14 componds IIa, IIb, IIIa, Va, VIb, VIIb, VIIIb, VIIIh, IXa, IXb, Xb, XIb, XIIa and XIIb had high activity against Gram-positive and Gram-negative bacteria ranging from 0.25-2 og/mL. The most potent compounds were investigated for their mechanism of action as DNA Gyrase inhibitors compound IXa was the most potent DNA Gyrase inhibitors with IC50 0.68 oM compared to ciprofloxacin (IC50 0.85 oM). Molecular modeling was performed to assess the binding of these active compounds with DNA Gyrase

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