Synthesis and antitumor activities of novel Mannich base derivatives derived from natural flavonoids

Abstract

In our current study, a series of reactions with isolated natural flavonoids (2-phenylchromen-4-one) and flavanone (2,3-dihydro-2-phenylchromen-4-one) through Mannich base was carried out by a one-pot three-component reaction. Their structure-activity relationship study (SAR) reveals the anticancer activity of natural compounds and their Mannich bases. The flavones were substituted by imine at position C-8, while in the flavanones, the reaction takes place at positions C-8 and C-3. Spectroscopic techniques characterized all the isolated and newly synthesized derivatives. Anticancer activity was checked on HeLa and MCF-7 (cancer cell lines) and BHK-21 (normal cell line). Using propidium iodide (PI) and DAPI staining as fluorescence microscopic imaging was confirmed the Apoptotic effect of potent compound. Further, it was evaluated by cell cycle analysis through flow-cytometry, reactive oxygen species and lactate dehydrogenase production. The caspase-9 and -3 activity were estimated by mitochondrial membrane potential. Derivative of naringenin, ((2S)-4′,5,7-Trihydroxyflavan-4-one) where reactions occur at position C-3 were active than others.