Targeting SmCB1: Perspectives and Insights to Design Antischistosomal Drugs

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...

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Bibliographic Details
Published in:	Current medicinal chemistry Vol. 31; no. 16; p. 2264
Main Authors:	Dos Santos Nascimento, Igor José, Albino, Sonaly Lima, da Silva Menezes, Karla Joane, de Azevedo Teotônio Cavalcanti, Misael, de Oliveira, Mozaniel Santana, Mali, Suraj N, de Moura, Ricardo Olimpio
Format:	Journal Article
Language:	English
Published:	United Arab Emirates 01-01-2024
Subjects:	Animals Drug Design Humans Schistosoma mansoni - drug effects Schistosoma mansoni - enzymology Schistosomicides - chemistry Schistosomicides - pharmacology Schistosomicides - therapeutic use cysteine protease parasitic diseases Schistosoma drug discovery SmCB1 molecular modeling
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Summary:	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, 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 , His , and Asn . 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.
ISSN:	1875-533X
DOI:	10.2174/0109298673255826231011114249