Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

Abstract

Synthesis, spectral studies, hydrolysis kinetics and pharmacodynamic profile of mefenamic acid prodrugs

Author(s): Mamdouh M. Ali, Abeer H. Abdel-Halim,Abeer E. Mahmoud, Monira A. Abd El-Kader, Saeed M. Soliman

Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality rates. The present study aimed to investigate the chemopreventive effects of prepared sulfated oligosaccharide compounds(Maltose SO4, Raffinose SO4, Stachyose SO4, Chondroitin-6-sulfate and Maltohexaose SO4)by studying their ability to inhibit, reverse or restrict the development of cancer through inhibiting the metastasis and angiogenesis of tumor in diethylnitrosamine (DENA) induced hepatocarcinogenesis in rats. To elucidate the mechanism by which the prepared sulfated oligosaccharidesexert their antitumor activities in the animals-bearing tumor the following parameters were determined including:aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), total bilirubinas liver function test;hepatic tyrosine kinase (TRK) and cytochrome P450 2E1 (CYP 2E1) as marker for tumor progression;vascular endothelial growth factor (VEGF) and sialic acid (TSA) as markers of angiogenesis;heparanase and elastase as marker of metastasis. Liver histopathological analysis was also evaluated. Carcinogenic rats recorded drastic elevation in all parameters under investigation whichconfirmed by histopathological distortion in the tissue organization with hyperchromatism, hyperplasia, proliferating hepatocytes.Prepared sulfated oligosaccharides supplementation at 1/10 of theirmedian lethal dose, LD50, significantly improved the biochemical and histopathological changes induced by DENA in the order of Maltose SO4>Maltohexaose SO4>Stachyose SO4>Raffinose SO4> Chondroitin-6- sulfate. Taken together, our results demonstrate that the tested compounds especially Maltose SO4 and Maltohexaose SO4 may be potent anticancer agents for inclusion in modern clinical trials after more investigations on higher animals.


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