Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7 H -pyrimido[4,5- b ][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 ( 20,21 ) a - g and ( 23,24 ) a - g and six series of 1,3,5-triazine-based pyrimido[4,5- b ][1,4]diazepines ( 28 - 33 ) a - g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b , d , 21a,b , d , 23a , d - g , 24a - g and the pyrimido[4,5- b ][1,4]diazepines 29e , g , 30g , 31a , b , e - g , 33a , b , e - g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI 50 values between 0.01 and 100 μM and LC 50 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 N. gonorrhoeae , S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5- b ][1,4]diazepines (MICs: 0.25-62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus , respectively (MICs = 62.5 μg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.