A Promising Therapeutic Scaffold Fusing Chalcone/Coumarin Targeting Colorectal Cancer: Design, Synthesis, Biological and ADME‐tox Modelling

Author:

Ramírez‐Bedoya Camilo1,Cardona‐Galeano Wilson1,Herrera‐Ramírez Angie1,Yepes Andrés F.1

Affiliation:

1. Química de Plantas Colombianas Institute of Chemistry Faculty of Exact and Natural Sciences University of Antioquia Calle 70 No. 52–21 Medellín Colombia

Abstract

AbstractEight novel compounds incorporating chalcone and coumarin features, namely chalcone‐coumarin‐ hybrid molecules, were designed, synthetized, and evaluated for their activity against human colorectal carcinoma SW480 cell line. According to the results observed, the hybrid with a 2,3‐dimetoxysubstitution pattern displayed the highest activity at the conditions evaluated, with an IC50 value of 25.18±1.12 μM, being even more active than the reference drug (5‐fluorouracil) and the parental compound (7‐methylcoumarin). In addition, this hybrid compound exhibited significant antiproliferative activity in a time‐ and concentration dependent way, suggesting rather a cytostatic or cytotoxic effect. Moreover, a theoretical drug‐like/pharmacokinetics/toxicological study suggested that the most promising hybrid would have a great chance to advance to further preclinical studies as anti‐cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of chalcone‐coumarin conjugates, particularly the 2,3‐dimetoxysubstituited molecule to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer.

Publisher

Wiley

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