Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7-pyrimido[4,5-][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents.

This study presents the synthesis of four series of novel hybrid chalcones ()- and ()- and six series of 1,3,5-triazine-based pyrimido[4,5-][1,4]diazepines (-)- and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones ,, ,, ,-, - and the pyrimido[4,5-][1,4]diazepines ,, , ,,-, ,,- exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI values between 0.01 and 100 μM and LC values in the range of 4.09 μM to >100 μM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against , (ATCC 43300), and were exhibited by the pyrimido[4,5-][1,4]diazepines (MICs: 0.25-62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone and triazinyloxy-chalcone were the most active compounds against and and , respectively (MICs = 62.5 μg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.