Decrease in Cell Viability of Breast Cancer Cells by a Di-Hydroxylated Derivative of N-(2-hydroxyphenyl)-2-Propylpentanamide

Author(s):

Norma L. Galindo-Alvarez, Humberto L. Mendoza-Figueroa, Martha C. Rosales-Hernández, Norbert Bakalara and José Correa-Basurto*   Pages 1802 - 1812 ( 11 )

Abstract:

<P>Background: A preliminary study of the biotransformation by cytochrome P450 enzymes (CYP) of N-(2- hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), an HDAC inhibitor, led to the synthesis of two hydroxylated derivatives: N-(2,4-dihydroxyphenyl)-2-propylpentanamide (5a) and N-(2,5-dihydroxyphenyl)-2-propylpentanamide (5b). <P> Objective: The study aims to evaluate the anti-proliferative activity of these di-hydroxylated derivatives in breast cancer cell lines. <P> Methods: MTT assays were conducted in MCF-7 and MDA-MB-231 cell lines. Additionally, in silico studies were carried out to evaluate the affinity of these derivatives with the HDAC1 enzyme. <P> Results: Results showed that only 5b possess an enhanced anti-proliferative effect in breast cancer cell lines MCF-7 and MDA-MB-231. Docking studies revealed that the presence of hydroxyl groups, as well as the position of the additional hydroxyl groups, could have an impact on HDAC1 affinity and could explain the lack of activity of compound 5a. <P> Conclusion: A priori, these results hypothesize that anti-proliferative activity of 5b could be related to HDAC1 inhibition and thus anti-proliferative activity in breast cancer cells.</P>

Keywords:

Antiproliferation, breast cancer, HO-AAVPA, HDAC inhibitor derivatives, dihydroxylation, TNBC.

Affiliation:

Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation). Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation). Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, Laboratorio de Biofísica y Biocatálisis, Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, Institut des Neurosciences de Montpellier, INM, U-1051, Univ. Montpellier, CHU de Montpellier, ENSCM, INSERM, Montpellier, Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation). Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340

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