engleski

Insights into biological activity of SAHAquines, hybrids based on SAHA and aminoquinoline motifs

SAHAquines represent hybrid drugs, developed as a combination of SAHA, an anticancer drug with weak antiplasmodial activity, and an antiplasmodial agent bearing 8-aminoquinoline or 4-aminoquinoline motifs with low anticancer activity, i.e. primaquine (PQ), chloroquine (CQ) or mefloquine (MQ). Two generations of SAHAquines were designed, prepared and biologically evaluated. In the 1st generation SAHA motif was combined with PQ. The designed hybrid drugs differ in linker length/type and/or functional groups: compounds 1 are esters, 2 are carboxylic acids, 4 are unsubstituted and 3 and 5 are O-benzyl and O- methyl substituted hydroxamic acids. 2nd generation of SAHAquines, fumaric acid diamides 6−8 were designed as Michael acceptors. One of the amide bonds was achieved with a terminal amino group of PQ, CQ or MQ, while the other amide bond was realized with halogen anilines. To fully explore the biological potential of SAHAquines, an extensive screening was performed: antiproliferative (a panel of cancer cell lines), antiplasmodial (both erythrocytic and hepatic stages), antibacterial (G(+) and G(−) bacteria and several Mycobacterium species) and antiviral (a series of DNA and RNA viruses) activity was evaluated. So far, results have shown that SAHAquines of the 1st generation exert antiproliferative and antiplasmodial activity on both erythrocytic and hepatic stages, while the 2nd generation SAHAquines exhibit significant biofilm eradication capacity. Further testing is in progress.

primaquine ; aminoquinoline ; SAHA ; biological activity

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