1-Benzamido-1,4-dihydropyridine derivatives as anticancer agents: in vitro and in vivo assays

1,4-Dihydropyridine is a privileged scaffold present in many bioactive molecules, from coenzymes to commercially available drugs. Among other interesting properties, it has been found good anticancer activity some of these 1,4-DHPs, therefore research groups are trying develop new compounds based on this structural core. For purpose, work, family 23 1,4-dihydropyridines synthesized using hydrazide and malononitrile derivatives as precursors. This straightforward catalytic process given rise the desired products with moderate excellent yields. All have tested against four different cancer cell lines [HeLa (human cervical carcinoma), Jurkat (leukemia), A549 lung cancer) MIA PaCa-2 (pancreatic cancer)] establish preliminary structure–activity relationship. From study, among best candidates, we chose 4-chlorophenyl 4-(trifluoromethyl)phenyl ring synthesize second generation molecules enhanced cytotoxicity, modifying substituent N-heterocyclic position (acylhydrazine moieties). With compounds, successfully decreased IC50 until 7 µM. An in-depth analysis their biological properties suggests that promising trigger non-conventional death mechanism known paraptosis. Moreover, photophysical show cases an long wavelength emission excitation, potentially leading biosensors or theragnostic agents. Finally, vivo assays concerning acute toxicity mice two most active (with alkyl chain seven carbon atoms acylhydrazine moiety) demonstrated even dosed at thousands fold corresponding values (2500 3300 times more concentrated than for studied), there was no sign harmful effects subjects, results support use further studies discover