Phthalocyanine hybrids with fused heterocycles: Cytotoxic profiles and DNA binding potential

This study focuses on the synthesis, characterization, and biological evaluation of novel phthalonitrile and phthalocyanine derivatives with enhanced solubility and structural modifications to improve their medical applications. A series of phthalocyanine compounds 4a,b; 6a,b; and 11a-g were synthesized via a reaction of novel phthalonitrile derivatives 3a,b; 5a,b; 8a; 9a; and 10a-c via different routes. The synthesized compounds were structurally confirmed using IR, NMR, and UV-vis spectroscopy. Their cytotoxicity was evaluated against HepG2 and MCF-7 cancer cell lines, revealing strong to very strong anticancer activity for several derivatives, particularly compounds 3b, 10b, 10c, and 11f. The molecular docking study was stimulated to estimate the bindings between the synthesized compounds and a target protein; compound 11f displayed good binding affinity (S [Formula: see text] -8.5122 kcal/mol), followed by hybrid 10c (S [Formula: see text] -6.7083 kcal/mol) and hybrid 10b (S [Formula: see text] -6.5120 kcal/mol), over the formation of multiple hydrogen-acceptor bonds. Additionally, SwissADME analysis predicted favorable pharmacokinetic properties for several candidates, highlighting their drug-like potential. These findings contribute to the development of new phthalocyanine-based therapeutics with enhanced cytotoxic properties and targeted biological interactions.