Novel Antischistosomal Drug Targets: Identification of Alkaloid Inhibitors of SmTGR via Integrated In Silico Methods
Valéria V. M. Paixão,
Yria J. A. Santos,
Adriana O. Fernandes,
Elaine S. Conceição,
Ricardo P. Rodrigues,
Daniela A. Chagas-Paula,
Silvio S. Dolabella,
Tiago B. Oliveira
Affiliations
Valéria V. M. Paixão
Posgraduate Program in Chemistry—PPGQ, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil
Yria J. A. Santos
Posgraduate Program in Chemistry—PPGQ, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil
Adriana O. Fernandes
Postgraduate Program in Biotechnology—PROBIO, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil
Elaine S. Conceição
Posgraduate Program in Chemistry—PPGQ, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil
Ricardo P. Rodrigues
Faculty of Pharmaceutical Sciences, University of Campinas, Rua Cândido Portinari, 200, Cidade Universitária, Campinas 13083-871, SP, Brazil
Daniela A. Chagas-Paula
Chemistry Institute, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, Alfenas 37130-001, MG, Brazil
Silvio S. Dolabella
Postgraduate Program in Parasite Biology, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil
Tiago B. Oliveira
Posgraduate Program in Chemistry—PPGQ, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil
Schistosomiasis mansoni is a neglected tropical disease caused by the parasite Schistosoma mansoni, affecting approximately 200 million people annually. Currently, treatment relies primarily on a single drug, praziquantel (PZQ), which shows limited efficacy against the parasite’s immature forms. As a result, Thioredoxin Glutathione Reductase from S. mansoni (SmTGR) has emerged as a promising target for novel drug development. This study presents the development of integrated in silico methods to identify alkaloids from medicinal plants with potential activity against S. mansoni. Fourteen alkaloids were identified, with predicted activity ranging from 61.3 to 85.2%. Among these, lindoldhamine and daibucarboline A demonstrated, for the first time, potential SmTGR inhibition, with probabilities of 85.2% and 75.8%, respectively. These findings highlight the potential of these alkaloids as promising candidates for the development of new therapies against schistosomiasis.
