TY - JOUR
T1 - Decrease in Cell Viability of Breast Cancer Cells by a Di-Hydroxylated Derivative of N-(2-hydroxyphenyl)-2-Propylpentanamide
AU - Galindo-Alvarez, Norma L.
AU - Mendoza-Figueroa, Humberto L.
AU - Rosales-Hernández, Martha C.
AU - Bakalara, Norbert
AU - Correa-Basurto, José
N1 - Publisher Copyright:
© 2022 Bentham Science Publishers.
PY - 2022
Y1 - 2022
N2 - 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). Objective: The study aims to evaluate the anti-proliferative activity of these di-hydroxylated derivatives in breast cancer cell lines. 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. 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 addi-tional hydroxyl groups, could have an impact on HDAC1 affinity and could explain the lack of activity of compound 5a. 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.
AB - 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). Objective: The study aims to evaluate the anti-proliferative activity of these di-hydroxylated derivatives in breast cancer cell lines. 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. 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 addi-tional hydroxyl groups, could have an impact on HDAC1 affinity and could explain the lack of activity of compound 5a. 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.
KW - Antiproliferation
KW - HDAC inhibitor derivatives
KW - HO-AAVPA
KW - TNBC
KW - breast cancer
KW - dihydroxylation
UR - http://www.scopus.com/inward/record.url?scp=85127966355&partnerID=8YFLogxK
U2 - 10.2174/1871520621666210915100826
DO - 10.2174/1871520621666210915100826
M3 - Artículo
C2 - 34525926
AN - SCOPUS:85127966355
SN - 1871-5206
VL - 22
SP - 1802
EP - 1812
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
IS - 9
ER -