Natural and synthetic chalcones derivatives are known for their remarkable biological potential including anti-cancer, anti-diabetic and anti-inflammatory activities etc... In the current work, 127 novel chalcone derivatives providing functionalized libraries of alkoxylated chalcones, heterocyclic chalcone hybrids, α-substituted chalcones and podophyllotoxin analogs have been synthesized, characterized and evaluated for their anti-tumor activity.
α-Amide chalcone derivatives were found active at nanomolar concentration in breast (HCC1954) and colorectal (HCT116) cancer cell lines. The compounds acted as p53 stabilizing agent and caused cell cycle arrest at G2/M phase. More importantly, these compounds were found to overcome multidrug resistance in MDR-1 overexpressing ovarian (A2780-Pac-Res) and cervical (KB-V1) cancer cell lines.
Alkoxylated chalcones showed selectivity against leukaemia cell line, MV-411 (acute myeloid leukaemia cell line) and K562 (chronic myelod leukaemia cell line) providing novel compounds, with the ability to act as FLT3 and BCR/ABL inhibitors. Heterocyclic chalcone hybrids i.e imidazopyridine chalcone hybrids with trifluoromethyl substitution on heterocyclic ring and differently substituted phenyl ring showed 3-28 µM half maximal growth inhibition in breast cancer cell line (Cal-51). Library of novel 4-aza podophyllotoxin analogs and their N-methylated derivatives were also found active in Cal-51 cell line with the most potent 4-aza podophyllotoxin analog showed half maximal inhibitory concentration value 1.67 µM.
A substantial number of new compounds has been synthesized within presented projects, thus enriching the current scope of potential inhibitors.