Synthesis and biological evaluation of new curcumin analogues as antioxidant and antitumor agents: Molecular modeling study

New curcumin analogues have been synthesized and their antioxidant activities were investigated by measuring their free radical scavenging capacities. The in vitro and in vivo antitumor activities of the synthesized compounds on Ehrlich ascites carcinoma (EAC) cell line were evaluated. 4-(4-Chlorophenyl)-2-(5-ethyl-7-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c] pyridin-2-yl)thiazole 7h showed excellent antineoplastic activity in both in vitro and in vivo studies more than that of tested compounds and reference drug, cisplatin. Different molecular modeling studies were performed, where docking of compound 7h into telomerase active site suggested that it could exert its antitumor potential by telomerase inhibition. We synthesized novel curcumin analogues with antioxidant and anticancer activities. Compound 7h showed remarkable activity having 82.60% inhibition of the ABTS radical cation, 100% death of cultured EAC cells and 82% tumor growth inhibition. Also docking studies showed that compound 7h is well fitted in the active site of telomerase enzyme with Gln B367, Lys B169 and Asn B303 aminoacid residues. [Display omitted] •New curcumin analogues were synthesized.•Their antioxidant, in vitro and in vivo antitumor activities were evaluated.•Compound 7h showed higher antitumor activity than that of cisplatin.•Docking simulation of 7h into the telomerase active site was performed.•It suggested that 7h could exert its antitumor potential by telomerase inhibition.