Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host

Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Juan D MayaA Morello

Abstract

Current knowledge of the biochemistry of Trypanosoma cruzi has led to the development of new drugs and the understanding of their mode of action. Some trypanocidal drugs such as nifurtimox and benznidazole act through free radical generation during their metabolism. T. cruzi is very susceptible to the cell damage induced by these metabolites because enzymes scavenging free radicals are absent or have very low activities in the parasite. Another potential target is the biosynthetic pathway of glutathione and trypanothione, the low molecular weight thiol found exclusively in trypanosomatids. These thiols scavenge free radicals and participate in the conjugation and detoxication of numerous drugs. Inhibition of this key pathway could render the parasite much more susceptible to the toxic action of drugs such as nifurtimox and benznidazole without affecting the host significantly. Other drugs such as allopurinol and purine analogs inhibit purine transport in T. cruzi, which cannot synthesize purines de novo. Nitroimidazole derivatives such as itraconazole inhibit sterol metabolism. The parasite's respiratory chain is another potential therapeutic target because of its many differences with the host enzyme complexes. The pharmacolog...Continue Reading

References

Dec 15, 1975·Biochemical and Biophysical Research Communications·R P Mason, J L Holtzman
Oct 1, 1979·Archives of Biochemistry and Biophysics·R Docampo, A O Stoppani
Feb 1, 1975·Journal of the American Oil Chemists' Society·A L Branen
Jan 1, 1992·Annual Review of Microbiology·A H Fairlamb, A Cerami
Jan 1, 1988·Comparative Biochemistry and Physiology. C, Comparative Pharmacology and Toxicology·A Morello
Jan 1, 1987·Transactions of the Royal Society of Tropical Medicine and Hygiene·L S Filardi, Z Brener
Dec 1, 1973·Experientia·A O Stoppani, J F De Boiso
Jul 1, 1968·The American Journal of Medicine·G B ElionG H Hitchings
May 18, 1981·FEBS Letters·W E Gutteridge, M J Davies
Mar 1, 1981·The Journal of Experimental Medicine·B A ArrickA Cerami
Mar 1, 1994·Comparative Biochemistry and Physiology. Pharmacology, Toxicology and Endocrinology·A MorelloY Repetto
Apr 1, 1996·Planta medica·S Sepúlveda-Boza, B K Cassels
Oct 1, 1996·Molecular and Biochemical Parasitology·R L Krauth-Siegel, H Lüdemann
Dec 10, 1997·Journal of the National Cancer Institute·H H BaileyG Wilding
Jul 29, 1998·Chemico-biological Interactions·M E Anderson
Jul 29, 1998·Chemico-biological Interactions·P CalvertP J O'Dwyer
Aug 6, 2000·Tropical Medicine & International Health : TM & IH·P KapoorR Madhubala
Jan 2, 2001·Journal of the American Veterinary Medical Association·K K BradleyL V Kirchhoff
Jan 21, 2001·The Journal of Biological Chemistry·M DormeyerR L Krauth-Siegel
Jun 15, 2001·Phytotherapy Research : PTR·I BergerW Kubelka
Jun 26, 2001·Journal of Natural Products·J A Bravo BC Lavaud
Jul 4, 2001·The Journal of Biological Chemistry·A MontalvettiR Docampo
Jul 27, 2001·Current Pharmaceutical Design·K AugustynsA Haemers
Aug 24, 2001·Biological Chemistry·C de OliveiraM L Oliva
Sep 26, 2001·Parasitology Research·M M CabralG A Schaub
Oct 10, 2001·Bioorganic & Medicinal Chemistry Letters·E del OlmoA San Feliciano

❮ Previous
Next ❯

Citations

Feb 16, 2010·Journal of Bioenergetics and Biomembranes·M P FernandesA E Vercesi
Mar 31, 2012·Antioxidants & Redox Signaling·Lucía PiacenzaRafael Radi
Oct 13, 2009·The Journal of Antimicrobial Chemotherapy·José A Pérez-MolinaRogelio López-Velez
Jul 8, 2009·Antimicrobial Agents and Chemotherapy·Jean Jerley N SilvaDouglas W Franco
Aug 8, 2012·Antimicrobial Agents and Chemotherapy·Alejandra B CiccarelliMaria Elisa Lombardo
Feb 9, 2012·Antimicrobial Agents and Chemotherapy·Shanshan HeMark E Drew
May 17, 2013·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Soodabeh SaeidniaAzita Haddadi
Feb 5, 2009·PLoS Neglected Tropical Diseases·Chiung-Kuang ChenLarissa M Podust
Aug 4, 2012·PLoS Neglected Tropical Diseases·Shamila S GunatillekeLarissa M Podust
May 24, 2014·PLoS Neglected Tropical Diseases·Andrea TrochineCarlos Robello
Oct 20, 2010·Drug Design, Development and Therapy·Werner Apt
Sep 4, 2012·Parasitology Research·Fabiana Oliveira Dos Santos GomesIvan da Rocha Pitta
Mar 19, 2014·Experimental Parasitology·Andrea TrochineCarlos Robello
Mar 6, 2009·Journal of Molecular Modeling·Fábio Alberto de MolfettaCarlos Alberto Montanari
Jul 28, 2012·Parasitology Research·Viviane Rodrigues EsperandimSérgio de Albuquerque
Jul 30, 2014·European Journal of Medicinal Chemistry·Anna KryshchyshynRoman Lesyk
Nov 2, 2013·Future Medicinal Chemistry·Roberto Figueroa GuíñezJuan Diego Maya
Oct 23, 2013·Future Medicinal Chemistry·Benjamín Aguilera-VenegasHernán Speisky
Mar 4, 2009·Expert Review of Anti-infective Therapy·Rodolfo ViottiAlejandro Armenti
Apr 8, 2016·International Journal for Parasitology. Drugs and Drug Resistance·Nir QvitDaria Mochly-Rosen
Jul 17, 2015·Drug Development and Industrial Pharmacy·M S GualdesiM A Raviolo
May 16, 2012·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Christian A Díaz-UrrutiaJuan D Maya
Apr 13, 2010·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lilian T Düsman ToninMaria Helena Sarragiotto
Sep 9, 2009·Experimental Parasitology·Rodrigo López-MuñozJuan D Maya
Sep 29, 2009·European Journal of Medicinal Chemistry·Mariana PaganoLucía Otero
Jul 25, 2009·International Journal of Cardiology·Carine Muniz RibeiroDanilo Wilhelm Filho
Mar 17, 2009·International Immunopharmacology·María Fernanda PascuttiEsteban Serra
Jul 1, 2008·Free Radical Biology & Medicine·Florencia IrigoínRafael Radi
Jul 17, 2015·Cancer Biology & Therapy·Karin Melanie Cabanillas StanchiUrsula Holzer
Jul 24, 2008·Cellular Microbiology·Nathalie VonlaufenWilliam J Sullivan
Mar 29, 2012·IUBMB Life·Patricia Silvia RomanoMaría Isabel Colombo
Jan 24, 2012·Drug Development Research·Cristiane MenezesWalderez O Dutra
Mar 28, 2016·European Journal of Medicinal Chemistry·Cristina Fonseca-BerzalVicente J Arán

❮ Previous
Next ❯

Related Concepts

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Shane R WilkinsonIan Cheeseman
Memórias do Instituto Oswaldo Cruz
José Rodriques Coura, S L de Castro
Trends in Parasitology
Simon L CroftJulio A Urbina
© 2022 Meta ULC. All rights reserved