AI Article Synopsis
- - A series of variously substituted quinoxaline compounds were synthesized to test their effectiveness as P-glycoprotein (Pgp) inhibitors, aiming to enhance the antiproliferative effects of common cancer drugs like doxorubicin in drug-resistant nasopharyngeal carcinoma cells.
- - The study compared these new compounds with previous quinoxaline derivatives, specifically looking for improved inhibition capabilities by substituting oxygen with sulfur in the chemical structure.
- - Biological assays revealed that while many of the new compounds showed good Pgp inhibitory activity, substituting oxygen for sulfur did not enhance effectiveness, with compound 3a being particularly effective and compound 13c targeting a different resistance mechanism.
Article Abstract
A series of quinoxalines variously substituted, namely 3-arylthiomethyl-1,6-dimethylquinoxalin-2-ones (6a-f), 3-arylthiomethyl-1-benzyl-7-trifluoromethylquinoxalin-2-ones (8a-g) and 2-arylthiomethyl-3-benzyloxy-6-trifluoro-methylquinoxalines (10a,b,e-h), were synthesized and compared with previous arylphenoxymethylquinoxalines (1a-f, 2a-f and 3a-b). The purpose was to verify whether the replacement of oxygen with sulphur atom and the insertion of different substituents on the phenyl side chain were able to improve the capability to inhibit the Pgp pump and restore the antiproliferative activity of clinically useful drugs, such as doxorubicin (Doxo), vincristine (VCR) and etoposide (VP16), in drug-resistant human nasopharyngeal carcinoma KB cells (KB(wt), KB(MDR), KB(7D) and KB(V20C)). Furthermore, 2,3-bis(aryloxy-methyl)-6-trifluoromethylquinoxalines (13a-c) were designed with the objective to evaluate the capability of the double side chain to potentiate the antiproliferative activity of the drugs tested. Biological assays showed that title compounds were, in general, endowed with good activity as Pgp inhibitors. In particular compound 3a, bearing 2-CONHPh substituent on phenoxymethyl side chain, resulted the most effective, while the double side chain (compound 13c) gives the ability to inhibit a different MRP pump (a membrane glycoprotein named mrp). Furthermore, we can conclude that replacement of oxygen with sulphur atom did not improve the biological activity.
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| http://dx.doi.org/10.2174/157340608784325197 | DOI Listing |
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