Repositorio
Institucional

Perez-Fehrmann, Marcia

Kesternich, Victor

Puelles, Arturo

Quezada, Victor

Salazar, Fernanda

Christen, Philippe

Castillo, Jonathan

Carcamo, Juan Guillermo

Castro-Alvarez, Alejandro

Nelson, Ronald

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3H)-quinazolinones 3N-substituted

ROYAL SOC CHEMISTRY

RSC ADVANCES

en

A novel series of 6-iodo-2-methylquinazolin-4-(3H)-one derivatives, 3a-n, were synthesized and evaluated for their in vitro cytotoxic activity. Compounds 3a, 3b, 3d, 3e, and 3h showed remarkable cytotoxic activity on specific human cancer cell lines when compared to the anti-cancer drug, paclitaxel. Compound 3a was found to be particularly effective on promyelocytic leukaemia HL60 and non-Hodgkin lymphoma U937, with IC50 values of 21 and 30 mu M, respectively. Compound 3d showed significant activity against cervical cancer HeLa (IC50 = 10 mu M). The compounds 3e and 3h were strongly active against glioblastoma multiform tumour T98G, with IC50 values of 12 and 22 mu M, respectively. These five compounds showed an interesting cytotoxic activity on four human cancer cell types of high incidence. The molecular docking results reveal a good correlation between experimental activity and calculated binding affinity on dihydrofolate reductase (DHFR). Docking studies proved 3d as the most potent compound. In addition, the three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis exhibited activities that may indicate the existence of electron-withdrawing and lipophilic groups at the para-position of the phenyl ring and hydrophobic interactions of the quinazolinic ring in the DHFR active site.

artículo original

"VK thanks the European Union Project ChemBioFight (grant 269301). The biological studies were supported by grants awarded by the ""Fondo Nacional de Desarrollo Cientifico y Tecnologico de Chile"" (Fondecyt 1150934) and ""Fondo de Financiamiento de Centros de Investigacion en areas Prioritarias"" (FONDAP 15110027). A. C.-A. thanks the OpenEye company for academic licenses. Powered@NLHPC: This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM-02).

VK agradece al proyecto ChemBioFight de la Unión Europea (subvención 269301). Los estudios biológicos fueron apoyados por subvenciones otorgadas por el ""Fondo Nacional de Desarrollo Científico y Tecnológico de Chile"" (Fondecyt 1150934) y el ""Fondo de Financiamiento de Centros de Investigación en áreas Prioritarias"" (FONDAP 15110027). A.C.-A. agradece a la empresa OpenEye por las licencias académicas. Powered@NLHPC: Esta investigación fue parcialmente respaldada por la infraestructura de supercomputación del NLHPC (ECM-02)."

10.1039/d2ra03684c

PDF

POTENT ANTIBACTERIAL AGENTS

TYROSINE KINASE INHIBITORS

CROSS-COUPLING REACTION

GROWTH-FACTOR RECEPTOR

SUBSTITUTED QUINAZOLINONES

BIOLOGICAL EVALUATION

THYMIDYLATE SYNTHASE

MEDICINAL CHEMISTRY

EFFICIENT SYNTHESIS

ANTICANCER ACTIVITY

Química

Multidisciplinar

POTENTES AGENTES ANTIBACTERIANOS

INHIBIDORES DE LA TIROSINA QUINASA

REACCIÓN DE ACOPLAMIENTO CRUZADO

RECEPTOR DEL FACTOR DE CRECIMIENTO

QUINAZOLINONAS SUSTITUIDAS

EVALUACIÓN BIOLÓGICA

TIMIDILATO SINTASA

QUÍMICA MEDICINAL

SÍNTESIS EFICIENTE

ACTIVIDAD ANTICÁNCER

Química Orgánica

Farmacología y Farmacia

Oncología

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3H)-quinazolinones 3N-substituted

21340

21352

artículo original

version publicada

CC BY NC 4.0

CC BY NC 4.0

acceso abierto

acceso abierto

WOS:000834799600001

UE 269301

ANID FONDECYT 1150934

ANID FONDAP 15110027

NLHPC ECM-02