SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

ChemistryOpen
Maja BeusBranka Zorc

Abstract

We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding. It includes the following steps: coupling reaction between primaquine and a dicarboxylic acid monoester, hydrolysis, a new coupling reaction with O-protected hydroxylamine, and deprotection. SAHAquines 5 a-d showed significant reduction in cell viability. Among the three human cancer cell lines (U2OS, HepG2, and MCF-7), the most responsive were the MCF-7 cells. The antibodies against acetylated histone H3K9/H3K14 in MCF-7 cells revealed a significant enhancement following treatment with N-hydroxy-N'-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}pentanediamide (5 b). Ethyl (2E)-3-({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)prop-2-enoate (2 b) and SAHAquines were the most active compounds against both the hepatic and erythrocytic stages of Plasmodium parasites, some of them at sub-micromolar concentrations. The results of our research suggest that SAHAquines are p...Continue Reading

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Citations

Aug 4, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maja BeusBranka Zorc
Oct 13, 2020·Molecular Diversity·Ivana PerkovićBranka Zorc
Oct 23, 2019·Acta Pharmaceutica : a Quarterly Journal of Croatian Pharmaceutical Society and Slovenian Pharmaceutical Society, Dealing with All Branches of Pharmacy and Allied Sciences·Branka ZorcIvana Perković
Jul 2, 2019·Acta Pharmaceutica : a Quarterly Journal of Croatian Pharmaceutical Society and Slovenian Pharmaceutical Society, Dealing with All Branches of Pharmacy and Allied Sciences·Maja BeusBranka Zorc
Jun 27, 2021·Analytical and Bioanalytical Chemistry·Mariana AsslanSimon Rousseau
May 18, 2021·Trends in Parasitology·Suellen Rodrigues MaranNilmar Moretti

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Methods Mentioned

BETA
histone acetylation
acetylation
NMR
column chromatography

Software Mentioned

package
. org
Chemicalize
drc
R
GraphPad Prism
ImageJ

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