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Purine Nucleoside Phosphorylase as a Molecular Target to Develop Active Compounds Against Mycobacterium Tuberculosis

Rodrigo G. Ducati(1*), André A. Souto(2), Rafael A. Caceres(3), Walter F. de Azevedo(4), Luiz A. Basso(5), Diógenes S. Santos(6)

(1) Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
(2) Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
(3) Faculdade de Biociências, Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Laboratório de Bioquímica Estrutural, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
(4) Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
(5) Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
(6) Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
(*) Corresponding author


DOI: https://doi.org/10.15866/irebic.v1i1.1490

Abstract


Despite the availability of chemotherapic and prophylactic approaches to fight consumption, human tuberculosis (TB) continues to claim millions of lives annually, mostly in developing nations, generally due to limited resources available to ensure proper treatment and where human immunodeficiency virus infections are common. Moreover, rising drug-resistant cases have worsened even further this picture. Accordingly, new therapeutic approaches have become necessary. The use of defined molecular targets could be explored as an attempt to develop new and selective chemical compounds to be employed in the treatment of TB. The present review highlights purine nucleoside phosphorylase, a component enzyme of the purine salvage pathway, as an attractive target for the development of new antimycobacterial agents, since this enzyme has been numbered among targets for Mycobacterium tuberculosis persistence in the human host. Enzyme kinetics and structural data are discussed to provide a basis to guide the rational anti-TB drug design.
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Keywords


Enzyme Kinetics and Structural Analysis; Human Tuberculosis; Mycobacterium Tuberculosis; Purine Nucleoside Phosphorylase; Rational Drug Development

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References


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