Synthesis and bioactivity evaluation of new pyrimidinone-5-carbonitriles as potential anticancer and antimicrobial agents

• Published in: Research on chemical intermediates 2018-04, Vol.44 (4), p.2685-2702
• Main Authors: Helwa, Amira A., Gedawy, Ehab M., Abou-Seri, Sahar M., Taher, Azza T., El-Ansary, Afaf K.
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antimicrobial agents; Biotechnology; Cancer; Catalysis; Chemistry; Chemistry and Materials Science; Derivatives; E coli; Fungicides; Gram-positive bacteria; Inorganic Chemistry; Lead compounds; Physical Chemistry; Synthesis
• ISSN: 0922-6168; 1568-5675
• DOI: 10.1007/s11164-018-3254-y

New series of pyrimidinone-5-carbonitriles 3a–i , 4a–e , 5a–c , 6 and 7 have been synthesized and explored for their activities as anticancer, antibacterial and antifungal agents. Investigation of the anticancer activity revealed that several newly synthesized derivatives displayed potent cytotoxic activity against different cancer cells. Among them, compound 3g was the most potent on the MCF-7, A549 and Caco-2 cell lines (IC 50  = 1.42, 1.98 and 9.50 μM, respectively), as compared with 5-fluorouracil (IC 50  = 1.71, 10.32 and 20.22 μM, respectively), while compound 3f was found especially effective against MCF-7 and Caco-2 cell lines (IC 50  = 1.48 and 16.15 μM, respectively). Furthermore, the antimicrobial evaluation showed that compounds 3f and 3g have potent antibacterial activity against Gram-positive bacteria Staphylococcus aureus (MIC = 4 and 8 μg/mL, respectively) and promising activity against Escherichia coli (IZ. = 19 and 17 mm, respectively). Meanwhile, compound 4b displayed the highest activity toward Bacillus subtilis (MIC = 8 μg/mL). In particular, the results suggested that hydrazone derivatives bearing heterocyclic rings 3f and 3g are good lead compounds for the future design of more potent anticancer or antimicrobial agents.