Developing new compounds with bioactivity, especially against tumors, targeting G-quadruplexes is of great importance. In this direction,
some new phthalimide-incorporating pyridine derivatives were synthesized using the phthalimido-acetophenone derivative 1 as a key precursor.
Three-component cyclocondensation of compound 1 with various aryl aldehydes and ethyl cyanoacetate or malononitrile utilizing ammonium
acetate as the nitrogen source afforded the 4-substituted-6-(4-phthalimidophenyl)pyridin-2-one-3-carbonitriles 2a-e or the 2-amino-4-
substituted-6-(4-phthalimidophenyl)pyridine-3-carbonitriles 3a,b, respectively. Moreover, the characterization of these derivatives was
identified on the basis of elemental analysis and spectroscopic tools. Additionally, the potency of the targeted molecules as anticancer agents
was assessed against two carcinogenic human cell lines, namely, colon cancer (HCT-116) and human prostate cancer (PC3) cells. They exhibited
promising cytotoxicity in which compounds 2a and 2b have the strongest potency comparable with doxorubicin (Dox). The conducted molecular
docking studies revealed a good correlation between the anti-cancer activities of compounds and their binding effectiveness with both c-MYC
and KRAS G-quadruplexes. |
