Synthesis and Biological Evaluation of New Quinazolin-4(3H)-One–Coumarin Hybrids Designed as Anticancer and Antibacterial Agents

Quinazolinone derivatives are well-known anticancer agents; anticancer properties are also part of the broad spectrum of biological activity of coumarins. Conjugates containing quinazolin-4(3H)-one and coumarin fragments linked by polymethylene bridges of varying lengths were designed to improve properties of both parental compounds and create new anticancer or antibacterial agents. 3-{3-[(4-Methyl-2-oxo-2H-chromen-7-yl)oxy]propyl}quinazolin-4(3H)-one was synthesized as the base compound. It demonstrated moderate cytotoxicity against leukemia (K562 and HL60) and neuroblastoma (SH-SY5Y) cells in vitro, combined with relatively low acute, subacute, and chronic toxicity in vivo. Conjugates with various substituents and linkers were then synthesized to evaluate the structure–activity relationship. A study of the synthesized compounds on cell cultures showed that the introduction of a methyl substituent into the benzene ring of the coumarin fragment led to both an increase in cytotoxicity and expansion of its spectrum of action. Testing of the hybrids against Gram-positive and Gram-negative bacteria revealed that the introduction of halogens into the quinazoline fragment in the compounds or the elongation of the linker led to the emergence of pronounced antibacterial properties, which were most clearly manifested against Acinetobacter baumanii. The possibility of directing activity of quinazoline-4(3H)-one–coumarin hybrids by varying the substituents and the length of the linker was shown.