TY - JOUR
T1 - Structure-based virtual screening of new benzoic acid derivatives as trypanosoma cruzi trans-sialidase inhibitors
AU - Vázquez-Jiménez, Lenci Karina
AU - Paz-González, Alma Delia
AU - Juárez-Saldivar, Alfredo
AU - Uhrig, María Laura
AU - Agusti, Rosalía
AU - Reyes-Arellano, Alicia
AU - Nogueda-Torres, Benjamín
AU - Rivera, Gildardo
N1 - Funding Information:
We thank Oscar Campetella and his group from the Uni-versidad Nacional General San Mart?n (UNSAM) Argentina, for their kind gift of transsialidase from T. cruzi. Support for this work from the Universidad de Buenos Aires, the CONICET and the ANPCyT is gratefully acknowledged. RA and MLU are research members of the CONICET. We wish to express our gratitude to the CONACyT (CB-2014-01, 241615) and the Secretar?a de Investigaci?n y Posgrado del Instituto Polit?cnico Nacional for the support granted (SIP-20190295, and SIP-20200495).
Funding Information:
We thank Oscar Campetella and his group from the Uni-versidad Nacional General San aMrtín U(NSAM) rAgentina, for their kind gift of trans-sialidase from T. cruzi. Support for this work from the Universidad de Buenos Aires, the CONICET and the ANPCyT is gratefully acknowledged. RA and MLU reaesrearch emmbers fohetOCNICET. eWiwsh to express our gratitude to the CONACyT (CB-2014-01, 241615) and the Secretaría de Investigación y Posgrado dl e Instituto Politécnico Nacional for the support granted (SIP-20190295, and SIP-20200495).
Publisher Copyright:
© 2021 Bentham Science Publishers.
PY - 2021
Y1 - 2021
N2 - Background: Chagas disease, caused by the parasite Trypanosoma cruzi, represents a worldwide epidemiological, economic, and social problem. In the last decades, the trans-sialidase enzyme of Trypanosoma cruzi has been considered an attractive target for the development of new agents with potential trypanocidal activity. Objective: In this work, the aim was to find new potential non-sugar trans-sialidase inhibitors using benzoic acid as a scaffold. Methods: A structure-based virtual screening of the ZINC15 database was carried out. Additionally, the enzyme and trypanocidal activity of the selected compounds was determined. Results: The results of this work detected 487 compounds derived from benzoic acid as potential trans-sialidase inhibitors with a more promising binding energy value (<-7.7 kcal/mol) than the known inhibi-tor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). In particular, two lead compounds, V1 and V2, turned out to be promising trans-sialidase inhibitors. Even though the trypanocidal activity displayed was low, these compounds showed trans-sialidase inhibition values of 87.6% and 29.6%, respectively. Conclusion: Structure-based virtual screening using a molecular docking approach is a useful method for the identification of new trans-sialidase inhibitors.
AB - Background: Chagas disease, caused by the parasite Trypanosoma cruzi, represents a worldwide epidemiological, economic, and social problem. In the last decades, the trans-sialidase enzyme of Trypanosoma cruzi has been considered an attractive target for the development of new agents with potential trypanocidal activity. Objective: In this work, the aim was to find new potential non-sugar trans-sialidase inhibitors using benzoic acid as a scaffold. Methods: A structure-based virtual screening of the ZINC15 database was carried out. Additionally, the enzyme and trypanocidal activity of the selected compounds was determined. Results: The results of this work detected 487 compounds derived from benzoic acid as potential trans-sialidase inhibitors with a more promising binding energy value (<-7.7 kcal/mol) than the known inhibi-tor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). In particular, two lead compounds, V1 and V2, turned out to be promising trans-sialidase inhibitors. Even though the trypanocidal activity displayed was low, these compounds showed trans-sialidase inhibition values of 87.6% and 29.6%, respectively. Conclusion: Structure-based virtual screening using a molecular docking approach is a useful method for the identification of new trans-sialidase inhibitors.
KW - Enzymatic inhibi-tion
KW - Molecular docking
KW - Trans-sialidase
KW - Trypanocidal activity
KW - Trypanosoma cruzi
KW - Virtual screening
UR - http://www.scopus.com/inward/record.url?scp=85103273747&partnerID=8YFLogxK
U2 - 10.2174/1573406416666200506084611
DO - 10.2174/1573406416666200506084611
M3 - Artículo
C2 - 32370720
AN - SCOPUS:85103273747
SN - 1573-4064
VL - 17
SP - 724
EP - 731
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 7
ER -
