In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones

Bioorganic & Medicinal Chemistry
Gabriela AguirreMario Faundez

Abstract

The in vitro growth inhibition activity of new thiosemicarbazone derivatives against the protozoan parasite Trypanosoma cruzi, the causative agent of American trypanosomiasis, are described. The designed compounds combine in the same molecule the thiosemicarbazone function, recently described as a potent cruzain-inhibitor moiety, and the recognised 5-nitrofuryl group, an oxidative stress promoter. Some of the derivatives were found to be very active against the cultured (epimastigote) form of the parasite, being 1.5-1.7-fold more active than the reference compound, Nifurtimox. Free radicals production was detected when the compounds were incubated in presence of mammalian-liver microsomes. The thiosemicarbazones' capacity to act as pharmacophore in the cruzain inhibition process was theoretically analysed. Frontier molecular orbital HOMO was found as an adequate descriptor in this process. Acute in vivo toxicity of two of the more active derivatives was evaluated. The results showed that these compounds are among the most potent 5-nitrofuryl derivatives tested against this parasite thus support further in vivo studies of some of these thiosemicarbazones.

References

Jul 30, 1999·Experimental Parasitology·M Almeida-de-FariaM J Alves
Mar 31, 2001·Journal of the American Veterinary Medical Association·UNKNOWN AVMA Panel on Euthanasia. American Veterinary Medical Association
Aug 17, 2001·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·C Olea-AzarR Araya-Maturana
Jan 2, 2003·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·C Olea-AzarWilliams Porcal

❮ Previous
Next ❯

Citations

Jan 22, 2013·Antimicrobial Agents and Chemotherapy·Christopher BotShane R Wilkinson
Jun 2, 2009·Chemical & Pharmaceutical Bulletin·Shikha Parmar, Yatendra Kumar
Mar 13, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Abdelmadjid BenmohammedPatrice Vanelle
Apr 18, 2014·Biological Trace Element Research·Cynthia SarniguetLucía Otero
Mar 20, 2014·European Journal of Medicinal Chemistry·Neera Raghav, Mamta Singh
Jul 30, 2014·European Journal of Medicinal Chemistry·Anna KryshchyshynRoman Lesyk
Jul 30, 2005·Expert Opinion on Investigational Drugs·Dietmar Steverding, Kevin M Tyler
Sep 29, 2009·European Journal of Medicinal Chemistry·Mariana PaganoLucía Otero
Feb 13, 2007·Biochemical Pharmacology·Annamaria BuschiniPaola Poli
Mar 11, 2006·European Journal of Medicinal Chemistry·Fikret KaratasSüleyman Servi
Oct 5, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Humayun PervezKhalid Mohammed Khan
Sep 11, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Elizandra Aparecida BrittaRedouane Borsali
Sep 17, 2005·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Carolina RigolHugo Cerecetto
Aug 21, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Dipak Kumar NayakMita Chatterjee Debnath
Jan 29, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shirani K HaraguchiCleuza C da Silva
May 3, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Esteban Rodríguez ArceDinorah Gambino
Oct 27, 2017·Current Medicinal Chemistry·Ana Cristina Lima LeiteGevanio Bezerra de Oliveira Filho
Mar 23, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Bruno DemoroAna Isabel Tomaz
Dec 25, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Gustavo H G TrossiniElizabeth Igne Ferreira
Mar 18, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Anand K HalveKiran Tiwari
Dec 6, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Bruno DemoroDinorah Gambino
Jun 20, 2012·Organic & Biomolecular Chemistry·Shailesh S DixitJyoti Chattopadhyaya
Nov 5, 2020·International Journal of Molecular Sciences·Alexander I KostyukDmitry S Bilan
Jul 11, 2006·European Journal of Medicinal Chemistry·Lucía OteroHugo Cerecetto
Dec 7, 2018·Chemical Reviews·Yih Ching OngGilles Gasser
Oct 9, 2009·Bioorganic & Medicinal Chemistry·Alejandra GerpeHugo Cerecetto

❮ Previous
Next ❯