Targeting SmCB1: Perspectives and Insights to Design Antischistosomal Drugs.

Autor:	Dos Santos Nascimento IJ; Pharmacy Department, Cesmac University Center, Maceió, 57051-160, Brazil.; Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande 58429-500, Brazil.; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Estadual da Paraíba, Campina Grande, 58429-500, Brazil., Albino SL; Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande 58429-500, Brazil., da Silva Menezes KJ; Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande 58429-500, Brazil.; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Estadual da Paraíba, Campina Grande, 58429-500, Brazil., de Azevedo Teotônio Cavalcanti M; Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande 58429-500, Brazil.; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Estadual da Paraíba, Campina Grande, 58429-500, Brazil., de Oliveira MS; Coordination of Botany-Laboratory Adolpho Ducke, Avenida Perimetral, Museu Paraense Emílio Goeldi, 1901, Belém, 66077-530, PA Brazil., Mali SN; Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga East, Mumbai, 400019, India., de Moura RO; Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia, Universidade Estadual da Paraíba, Campina Grande 58429-500, Brazil.; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Estadual da Paraíba, Campina Grande, 58429-500, Brazil.
Jazyk:	angličtina
Zdroj:	Current medicinal chemistry [Curr Med Chem] 2024; Vol. 31 (16), pp. 2264-2284.
DOI:	10.2174/0109298673255826231011114249
Abstrakt:	Neglected tropical diseases (NTDs) are prevalent in tropical and subtropical countries, and schistosomiasis is among the most relevant diseases worldwide. In addition, one of the two biggest problems in developing drugs against this disease is related to drug resistance, which promotes the demand to develop new drug candidates for this purpose. Thus, one of the drug targets most explored, Schistosoma mansoni Cathepsin B1 (SmCB1 or Sm31), provides new opportunities in drug development due to its essential functions for the parasite's survival. In this way, here, the latest developments in drug design studies targeting SmCB1 were approached, focusing on the most promising analogs of nitrile, vinyl sulphones, and peptidomimetics. Thus, it was shown that despite being a disease known since ancient times, it remains prevalent throughout the world, with high mortality rates. The therapeutic arsenal of antischistosomal drugs (ASD) consists only of praziquantel, which is widely used for this purpose and has several advantages, such as efficacy and safety. However, it has limitations, such as the impossibility of acting on the immature worm and exploring new targets to overcome these limitations. SmCB1 shows its potential as a cysteine protease with a catalytic triad consisting of Cys 100 , His 270 , and Asn 290 . Thus, design studies of new inhibitors focus on their catalytic mechanism for designing new analogs. In fact, nitrile and sulfonamide analogs show the most significant potential in drug development, showing that these chemical groups can be better exploited in drug discovery against schistosomiasis. We hope this manuscript guides the authors in searching for promising new antischistosomal drugs. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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