Identification, In Vitro Testing and Molecular Docking Studies of Microginins' Mechanism of Angiotensin-Converting Enzyme Inhibition

Author(s)

Paiva, Fernanda C. R. ^{[1, 2]} ; Ferreira, Glaucio Monteiro ^[3] ; Trossini, Gustavo H. G. ^[3] ; Pinto, Ernani ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Ave Prof Lineu Prestes 580, Bl 17, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Ave Prof Lineu Prestes 1374, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharm, Ave Prof Lineu Prestes 580, Bl 13, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: Molecules; v. 22, n. 12 DEC 2017.
• Web of Science Citations: 2

Abstract

Cyanobacteria are able to produce a wide range of secondary metabolites, including toxins and protease inhibitors, with diverse biological activities. Microginins are small linear peptides biosynthesized by cyanobacteria species that act against proteases. The aim of this study was to isolate and identify microginins produced by the LTPNA08 strain of Microcystis aeruginosa, as well as to verify their potential to inhibit angiotensin-converting enzyme (ACE; EC. 3.4.15.1) using in vitro and in silico methods. The fractionation of cyanobacterial extracts was performed by liquid chromatography and the presence of microginins was monitored by both LC-MS and an ACE inhibition assay. Enzyme inhibition was assayed by ACE with hippuryl-histidyl-leucine as the substrate; monitoring of hippuric acid was performed by HPLC-DAD. Isolated microginins were confirmed by mass spectrometry and were used to carry out the enzymatic assay. Molecular docking was used to evaluate microginin 770 (MG 770) and captopril (positive control), in order to predict similar binding interactions and determine the inhibitory action of ACE. The enzyme assay confirmed that MG 770 can efficiently inhibit ACE, with an IC50 equivalent to other microginins. MG 770 presented with comparable interactions with ACE, having features in common with commercial inhibitors such as captopril and enalaprilate, which are frequently used in the treatment of hypertension in humans. (AU)

• FAPESP's process: 14/50420-9 - Secondary metabolites from aquatic microrganisms and their impact on seafood and freshwater fish aquaculture
• Grantee: Ernani Pinto Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08757-3 - Bioprospection of Brazilian cyanobacterial directed in order to obtain cyanopeptides protease inhibitors
• Grantee: Fernanda Cristina Rodrigues de Paiva
• Support Opportunities: Scholarships in Brazil - Master