TY - JOUR
T1 - Synthesis, biological evaluation and molecular docking of new benzenesulfonylhydrazone as potential anti-trypanosoma cruzi agents
AU - Elizondo-Jimenez, Silvia
AU - Moreno-Herrera, Antonio
AU - Reyes-Olivares, Rogelio
AU - DorantesGonzalez, Edith
AU - Nogueda-Torres, Benjamín
AU - De Oliveira, Eduardo Alves Gamosa
AU - Romeiro, Nelilma C.
AU - Lima, Lídia Moreira
AU - Palos, Isidro
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2016 Bentham Science Publishers.
PY - 2016
Y1 - 2016
N2 - Background: Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and N-acylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. Methods: Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. Results: Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 μM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 μM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. Conclusion: Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound.
AB - Background: Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and N-acylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. Methods: Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. Results: Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 μM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 μM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. Conclusion: Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound.
KW - Benzenesulfonyl
KW - Chagas disease
KW - Cruzain
KW - Inhibitors
KW - N-propionyl benzenesulfonylhydrazone
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=85010433186&partnerID=8YFLogxK
U2 - 10.2174/1573406412666160701022230
DO - 10.2174/1573406412666160701022230
M3 - Artículo
C2 - 27396731
SN - 1573-4064
VL - 12
SP - 149
EP - 158
JO - Medicinal Chemistry
JF - Medicinal Chemistry
ER -