Non-Ribosomal Halogenated Protease Inhibitors from Cyanobacterial Isolates as Attractive Drug Targets

Author(s)

Silva-Stenico, M. E. ^[1] ; Rigonato, J. ^[1] ; Leal, M. G. ^[1] ; Vaz, M. G. M. V. ^[1] ; Andreote, A. P. D. ^[1] ; Fiore, M. F. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ctr Nucl Energy Agr, Mol Ecol Cyanobacteria Lab, BR-13400970 Piracicaba, SP - Brazil

• Document type: Review article
• Source: Current Medicinal Chemistry; v. 19, n. 30, p. 5205-5213, OCT 2012.
• Web of Science Citations: 6

Abstract

Cyanobacteria possess the ability to produce compounds with remarkable biological activity, and have thus attracted the attention of the pharmaceutical industry. Cyanopeptides acting as protease inhibitors have shown potential in the field of pharmacotherapy through regulation of abnormal physiological processes in the human body. Despite the already described cyanopeptide protease inhibitors, the search for new congeners is of considerable interest which may pave the way for more efficient molecules. In this study, the presence of the protease inhibitors aeruginosin and cyanopeptolin with non-, mono- and dichlorination and also genes coding for their synthetases was investigated in 90 cyanobacterial strains. Mass spectrometry analyses highlighted production of 91, 19 and 3 non-, mono-and dichlorinated congeners, respectively. The purified extract of Microcystis botrys SPC759 inhibited 61% of pepsin protease. PCR amplifications of aeruginosin and cyanopeptolin synthetase gene regions were observed in 41 and 28% of evaluated strains, respectively. The sequences obtained for the aerA-aerB (aeruginosin) and mcnC-mcnE (cyanopeptolin) gene regions grouped together with their homologues found in other cyanobacterial strains in the phylogenetic analyses with high bootstrap support. Antimicrobial activity assays performed using all intracellular extracts inhibited 31 and 26% of Gram-negative and Gram-positive pathogenic bacterial growth, respectively. The results of this study showed the production of aeruginosin and cyanopeptolin and the presence of their genes in several cyanobacterial genera for the first time besides the discovery of novel congeners. (AU)

• FAPESP's process: 10/09867-9 - Bioprospection of cyanobacteria: screening cyanopeptides for pharmaceutical and biotechnological applications
• Grantee: Maria Estela Stenico
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 09/15402-1 - Cyanobacteria of the Atlantic Forest phyllosphere: isolation, taxonomy and bioprospecting
• Grantee: Ana Paula Dini Andreote
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/05474-5 - Bioprospection of cyanobacteria: screening cyanopeptides for pharmaceutical and biotechnological applications
• Grantee: Maria Estela Stenico
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 10/18732-0 - Bioactive natural products from marine cyanobacteria
• Grantee: Marcelo Gomes Marçal Vieira Vaz
• Support Opportunities: Scholarships in Brazil - Doctorate