SYNTHESIS, STRUCTURAL CHARACTERIZATION, AND BIOLOGICAL EVALUATION OF NOVEL PICOLINIC ACID DERIVED PYRIDINYLAMINO CARBOXAMIDES AS POTENTIAL ANTICANCER AND ANTIBACTERIAL AGENTS

Abstract

The development of structurally diverse heteroaromatic scaffolds remains an important strategy in the search for bioactive small molecules with anticancer and antimicrobial potential. In the present study, a series of ten N,N disubstituted-4-(pyridin-2-ylamino) pyridine-2-carboxamide derivatives (IVa–IVj) was synthesized through a sequential transformation of picolinic acid involving formation of 4-chloropyridine-2-carbonyl chloride, amidation, and subsequent nucleophilic substitution with 4-aminopyridine. The synthesized derivatives were obtained in 63–72% yields and characterized using physicochemical and spectroscopic techniques. Their biological potential was investigated by in vitro cytotoxicity assessment against MCF-7, HT-29, and A549 human cancer cell lines using the MTT assay and by antibacterial screening against selected Gram-positive and Gram-negative bacterial strains using the cup-plate method. The derivatives exhibited variable biological activities depending on structural modification. Among the synthesized compounds, IVc demonstrated the most pronounced cytotoxic activity, with IC₅₀ values of 9.2, 7.50, and 16.2 µM against MCF-7, HT-29, and A549 cells, respectively. IVh also exhibited strong cytotoxicity, with corresponding IC₅₀ values of 12.8, 9.4, and 17.5 µM. Notably, IVc showed the strongest antibacterial activity, producing inhibition zones of 12–15 mm against the tested bacterial strains, while IVh exhibited zones of 10–14 mm. Although the reference agents cisplatin and ciprofloxacin showed greater activity under the respective assay conditions, IVc and IVh demonstrated a favorable overall biological profile. These findings identify the pyridinylamino-picolinamide scaffold, particularly derivatives IVc and IVh, as a promising starting point for further structural optimization and mechanistic investigation.