Targeting SmCB1: Perspectives and Insights to Design Antischistosomal Drugs


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Abstract

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 Cys100, His270, and Asn290. 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.

About the authors

Igor dos Santos Nascimento

Pharmacy Department,, Cesmac University Center

Author for correspondence.
Email: info@benthamscience.net

Sonaly Albino

Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia,, Universidade Estadual da Paraíba

Email: info@benthamscience.net

Karla da Silva Menezes

Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia,, Universidade Estadual da Paraíba

Email: info@benthamscience.net

Misael de Azevedo Teotônio Cavalcanti

Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia,, Universidade Estadual da Paraíba

Email: info@benthamscience.net

Mozaniel de Oliveira

, Coordination of Botany-Laboratory Adolpho Ducke, Avenida Perimetral, Museu Paraense Emílio Goeldi

Email: info@benthamscience.net

Suraj Mali

Department of Pharmaceutical Sciences and Technology, I, Institute of Chemical Technology

Email: info@benthamscience.net

Ricardo de Moura

Laboratório de Desenvolvimento e Síntese de Fármacos, Departamento de Farmácia, Universidade Estadual da Paraíba,

Email: info@benthamscience.net

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