Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, anti-inflammatory and antioxidant agents

Abstract Chalcones have been identified as interesting compounds with cytotoxicity, anti-inflammatory and antioxidant properties. In the present study, simple methoxychalcones were synthesized by Claisen–Schmidt condensation reaction and evaluated for above biological activities. The structures of the compounds were established by IR, 1 H NMR and mass spectral analysis. The data revealed that compound 3s (99–100% at 10 μM concentration) completely inhibit the selected five human cancer cell lines as compared to standard flavopiridol and gemcitabine (70–90% at 700 nM and 500 nM concentrations, respectively), followed by 3a , 3n, 3o, 3p, 3q, 3r . Among the tested compounds 3l , 3m , 3r , and 3s exhibited promising anti-inflammatory activity against TNF-α and IL-6 with 90–100% inhibition at 10 μM concentration. DPPH free radical scavenging activity was given by the compounds 3o , 3n , 3l , 3r , 3m , 3a , 3p , 3c and 3s at 1 mM concentration. Overall, 3s was obtained as lead compound with promising anticancer, anti-inflammatory and antioxidant activities. Bioavailability of compounds were checked by in vitro cytotoxicity study and confirmed to be nontoxic. The structure activity relationship (SAR) and in silico drug relevant properties (HBDs, HBAs, PSA, c  Log  P , ionization potential, molecular weight, E HOMO and E LUMO ) further confirmed that the compounds were potential candidates for future drug discovery study.