Repositorio
Institucional

Parra, Claudio

Bustos, Luis

Echiburu-Chau, Carlos

Castro-Alvarez, Alejandro

Bradshaw, Ben

Simirgiotis, Mario J.

Mellado, Marco

Cuellar, Mauricio

Cytotoxic Effects on Breast Cancer Cell Lines of Chalcones Derived from a Natural Precursor and Their Molecular Docking Analysis

MDPI

MOLECULES

en

This study aimed to determine the in vitro cytotoxicity and understand possible cytotoxic mechanisms via an in silico study of eleven chalcones synthesized from two acetophenones. Five were synthesized from a prenylacetophenone isolated from a plant that grows in the Andean region of the Atacama Desert. The cytotoxic activity of all the synthesized chalcones was tested against breast cancer cell lines using an MTT cell proliferation assay. The results suggest that the prenyl group in the A-ring of the methoxy and hydroxyl substituents of the B-ring appear to be crucial for the cytotoxicity of these compounds. The chalcones 12 and 13 showed significant inhibitory effects against growth in MCF-7 cells (IC50 4.19 +/- 1.04 mu M and IC50 3.30 +/- 0.92 mu M), ZR-75-1 cells (IC50 9.40 +/- 1.74 mu M and IC50 8.75 +/- 2.01 mu M), and MDA-MB-231 cells (IC50 6.12 +/- 0.84 mu M and IC50 18.10 +/- 1.65 mu M). Moreover, these chalcones showed differential activity between MCF-10F (IC50 95.76 +/- 1.52 mu M and IC50 95.11 +/- 1.97 mu M, respectively) and the tumor lines. The in vitro results agree with molecular coupling results, whose affinity energies and binding mode agree with the most active compounds. Thus, compounds 12 and 13 can be considered for further studies and are candidates for developing new antitumor agents. In conclusion, these observations give rise to a new hypothesis for designing chalcones with potential cytotoxicity with high potential for the pharmaceutical industry.

artículo original

This research was funded by ANID, grant number R15F10011. C.P. acknowledges Fondecyt 11190698. M.J.S. acknowledges Fondecyt 1220075. M.C. acknowledges Programa Formacion de Capital Humano Avanzado 21130456. M.M. acknowledges Postdoctoral Fondecyt 3180408.

Esta investigación fue financiada por ANID, subvención número R15F10011. CP reconoce Fondecyt 11190698. M.J.S. reconoce Fondecyt 1220075. M.C. reconoce Programa Formación de Capital Humano Avanzado 21130456. M.M. reconoce Postdoctorado Fondecyt 3180408.

10.3390/molecules27144387

PDF

antioxidant

bioactive compounds

breast cancer

cytotoxic

molecular docking

Senecio nutans

synthesis

ANTIPROLIFERATIVE ACTIVITY

STRUCTURAL REQUIREMENTS

DIHYDROFOLATE-REDUCTASE

PRENYLATED CHALCONES

DERIVATIVES

DESIGN

FLAVONOIDS

INHIBITORS

GLIDE

Bioquímica y Biología Molecular

Química

Multidisciplinar

antioxidante

compuestos bioactivos

cáncer de mama

citotóxico

acoplamiento molecular

Senecio nutans

síntesis

ACTIVIDAD ANTIPROLIFERATIVA

REQUISITOS ESTRUCTURALES

DIHIDROFOLATO-REDUCTASA

CHALCONES PRENILADOS

DERIVADOS

DISEÑO

FLAVONOIDES

INHIBIDORES

GLIDE

Cytotoxic Effects on Breast Cancer Cell Lines of Chalcones Derived from a Natural Precursor and Their Molecular Docking Analysis

artículo original

version publicada

CC BY 4.0

CC BY 4.0

acceso abierto

acceso abierto

ANID-FONDECYT 11190698

ANID-FONDECYT 1220075

ANID-FONDECYT 3180408

ANID-FONDECYT R15F10011]

ANID 21130456

ANID FONDECYT 11190698

ANID FONDECYT 1220075

ANID FONDECYT 3180408

ANID FONDECYT R15F10011]

WOS:000832154000001