Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable anti-tumor activity.

LAALI, KENNETH K.; CORREA-SMITS, SEBASTIAN J.; AKHTAR, SHAROON; CHANAN-KHAN, ASHER; GREVES, WILLIAM J.; TROENDLE, FREDERICK J.; MANNA, ALAK; NUKAYA, MANABU; ZWARYCZ, ANGELA T.; BOROSKY, GABRIELA L.; PAULUS, ANEEL; KENNEDY, GREGORY D.

CHEMMEDCHEM

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2018

1860-7179

In a continuing search for curcuminoid (CUR) compounds withantitumor activity, a novel series of heterocyclic CUR?BF2 adductsand CUR compounds based on indole, benzothiophene,and benzofuran along with their aryl pyrazoles were synthesized.Computational docking studies were performed to comparebinding efficiency to target proteins involved in specificcancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2,versus known inhibitor drugs. The majority presented verygood binding affinities, similar to, and even more favorablethan those of known inhibitors. The indole-based CUR?BF2 andCUR compounds and their bis-thiocyanato derivatives exhibitedhigh anti-proliferative and apoptotic activity by in vitro bioassaysagainst a panel of 60 cancer cell lines, more specificallyagainst multiple myeloma (MM) cell lines (KMS11, MM1.S, andRPMI-8226) with significantly lower IC50 values versus healthyPBMC cells; they also exhibited higher anti-proliferative activityin human colorectal cancer cells (HCT116, HT29, DLD-1, RKO,SW837, and Caco2) than the parent curcumin, while showingnotably lower cytotoxicity in normal colon cells (CCD112CoNand CCD841CoN).