Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity

Document Type

Article

Publication Date

9-19-2018

Abstract

In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole-based CUR–BF2 and CUR compounds and their bis-thiocyanato derivatives exhibited high anti-proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI-8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti-proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).

Publication Title

ChemMedChem

Volume

13

Issue

18

First Page

1895

Last Page

1908

Digital Object Identifier (DOI)

10.1002/cmdc.201800320

PubMed ID

30079563

ISSN

18607179

E-ISSN

18607187

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