Our work group designed and synthesized a promissory compound N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA is a HDAC1 inhibitor and antiproliferative in cancer cell lines. However, HO-AAVPA is poor water solubility and enzymatically metabolized.
View Article and Find Full Text PDFGlioblastoma multiforme (GBM) is account for 70% of all primary malignancies of the central nervous system. The median survival of human patients after treatment is around 15 months. There are several biological targets which have been reported that can be pursued using ligands with varied structures to treat this disease.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2021
The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER.
View Article and Find Full Text PDFBackground: Our research group has developed some Valproic Acid (VPA) derivatives employed as anti-proliferative compounds targeting the HDAC8 enzyme. However, some of these compounds are poorly soluble in water.
Objective: Employed the four generations of Polyamidoamine (G4 PAMAM) dendrimers as drug carriers of these compounds to increase their water solubility for further in vitro evaluation.
Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aβ) and oxidative stress in vivo is the scopolamine model.
View Article and Find Full Text PDFOncotarget
February 2019
[This corrects the article DOI: 10.18632/oncotarget.26077.
View Article and Find Full Text PDFBackground: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells.
Objective: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA.
Methods: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines.
Oncotarget
September 2018
N-(2'-Hydroxyphenyl)-2-propylpentanamide (OH-VPA) is a valproic acid (VPA) derivative with improved antiproliferative activity toward breast cancer (MCF-7, MDA-MB-231, and SKBr3) and human cervical cancer cell lines (HeLa) compared to that of VPA. However, the pharmacological mechanism of OH-VPA activity remains unknown. High-mobility group box 1 (HMGB1) is an important enzyme that is highly expressed in tumor cells and has a subcellular localization that is dependent on its acetylation or oxidative state.
View Article and Find Full Text PDFAnticancer Agents Med Chem
July 2019
Background: Recent reports have demonstrated the role of the G Protein-Coupled Estrogen Receptor 1 (GPER1) on the proliferation of breast cancer. The coupling of GPER1 to estrogen triggers cellular signaling pathways related to cell proliferation.
Objective: Develop new therapeutic strategies against breast cancer.
J Enzyme Inhib Med Chem
February 2017
Epigenetic alterations are associated with cancer and their targeting is a promising approach for treatment of this disease. Among current epigenetic drugs, histone deacetylase (HDAC) inhibitors induce changes in gene expression that can lead to cell death in tumors. Valproic acid (VPA) is a HDAC inhibitor that has antitumor activity at mM range.
View Article and Find Full Text PDFValproic acid (VPA) is extensively used as an anticonvulsive agent and as a treatment for other neurological disorders. It has been shown that VPA exerts an anti-proliferative effect on several types of cancer cells by inhibiting the activity of histone deacetylases (HDACs), which are involved in replication and differentiation processes. However, VPA has some disadvantages, among which are poor water solubility and hepatotoxicity.
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