New 3-piperonylcoumarins as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi

Bioorganic & Medicinal Chemistry
Anderson A de MarchiMônica T Pupo

Abstract

This article describes the synthesis and inhibitory activities of a series of new 3-piperonylcoumarins, designed as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi. The design was based on the structures of previously identified natural products hits. The most active synthesized derivatives contain heterocyclic rings at position 6. SAR studies, performed by electronic indices methodology (EIM), clustered the molecules in different groups due to the chemical substitutions regarding the biological activity. Molecular modeling studies by docking suggested a different binding mode for the most active derivatives, when compared to natural hit chalepin. Moreover, the coumarin ring seems to act only as a spacer group.

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Citations

Mar 23, 2013·Archives of Pharmacal Research·Marcela de Souza SantosRose Mary Zumstein Georgetto Naal
Nov 13, 2013·Future Medicinal Chemistry·Fernando V MalufRafael Vc Guido
Apr 22, 2006·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Juan Diego MayaAntonio Morello
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Sep 9, 2020·European Journal of Medicinal Chemistry·Andrea GalbiatiPaola Conti
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lutfun NaharSatyajit D Sarker

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