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Analysis of non-peptidic compounds as potential malarial inhibitors against Plasmodial cysteine proteases via integrated virtual screening workflow.
Musyoka, Thommas M; Kanzi, Aquillah M; Lobb, Kevin A; Tastan Bishop, Özlem.
Afiliación
  • Musyoka TM; a Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology , Rhodes University , P.O. Box 94, Grahamstown 6140 , South Africa.
  • Kanzi AM; a Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology , Rhodes University , P.O. Box 94, Grahamstown 6140 , South Africa.
  • Lobb KA; b Faculty of Natural and Agricultural Sciences, Department of Genetics, Forestry and Agricultural Biotechnology Institute (FABI) , University of Pretoria , Pretoria , South Africa.
  • Tastan Bishop Ö; a Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology , Rhodes University , P.O. Box 94, Grahamstown 6140 , South Africa.
J Biomol Struct Dyn ; 34(10): 2084-101, 2016 Oct.
Article en En | MEDLINE | ID: mdl-26471975
Falcipain-2 (FP-2) and falcipain-3 (FP-3), haemoglobin-degrading enzymes in Plasmodium falciparum, are validated drug targets for the development of effective inhibitors against malaria. However, no commercial drug-targeting falcipains has been developed despite their central role in the life cycle of the parasites. In this work, in silico approaches are used to identify key structural elements that control the binding and selectivity of a diverse set of non-peptidic compounds onto FP-2, FP-3 and homologues from other Plasmodium species as well as human cathepsins. Hotspot residues and the underlying non-covalent interactions, important for the binding of ligands, are identified by interaction fingerprint analysis between the proteases and 2-cyanopyridine derivatives (best hits). It is observed that the size and chemical type of substituent groups within 2-cyanopyridine derivatives determine the strength of protein-ligand interactions. This research presents novel results that can further be exploited in the structure-based molecular-guided design of more potent antimalarial drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium / Modelos Moleculares / Inhibidores de Cisteína Proteinasa / Proteasas de Cisteína / Antimaláricos Tipo de estudio: Diagnostic_studies / Screening_studies Idioma: En Revista: J Biomol Struct Dyn Año: 2016 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium / Modelos Moleculares / Inhibidores de Cisteína Proteinasa / Proteasas de Cisteína / Antimaláricos Tipo de estudio: Diagnostic_studies / Screening_studies Idioma: En Revista: J Biomol Struct Dyn Año: 2016 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Reino Unido