Synthesis of Novel Thiophene‐Chalcone Derivatives as Anticancer‐ and Apoptosis‐Inducing Agents

Abstract

AbstractA series of new thiophene linked chalcone hybrids has been designed and synthesized. The key intermediate thiophene‐2‐carbaldehyde 13 was synthesized by coupling furan and phenyl ring via Suzuki reaction. The new scaffolds were synthesized by base catalyzed condensation reaction from key intermediate with various substituted acetophenones to build the chalcone core. The conversion in this synthesis involves the following steps (i) Selective bromination, (ii) regioselective Suzuki coupling (iii) Various aromatic substituents were introduced by classical aldol condensation. We screened all compounds of this thiophene‐chalcone derivatives (15 a‐n) in selected cancer cell lines viz. Human breast (MCF‐7, MDA‐MB‐453) prostate cancer (PC‐3), lung (A549). The screened compounds showed good anticancer activity on two of the studied cell lines with best IC50 values of thiophene‐chalcone derivative 15 e (6.3±0.9 μM) on A549 and with GI50 values of compound 15 e (1.9±0.3 μM) on A549 cells. This strategy is operationally simple and works with a diverse range of substrates and warrants future investigations for further anticancer drug development.