Moreno, Leydi M.Quiroga, JairoAbonia, RodrigoCrespo, María del P.Aranaga, CarlosMartínez Martínez, LuisSortino, MaximilianoBarreto, MauricioBurbano, María E.Insuasty, Braulio2025-07-092025-07-092024Moreno, L. M., Quiroga, J., Abonia, R., Crespo, M. d. P., Aranaga, C., Martínez-Martínez, L., Sortino, M., Barreto, M., Burbano, M. E., & Insuasty, B. (2024). Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents. International Journal of Molecular Sciences, 25(7), 3623. https://doi.org/10.3390/ijms2507362316616596https://repositorio.usc.edu.co/handle/20.500.12421/7327This 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 GI50 values between 0.01 and 100 μM and LC50 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.en135-triazinesantibacterial activityanticancer activityantifungal activitychalconescytotoxicitydiazepinesArticle