Virtual screening of antibacterial compounds by similarity search of Enoyl-ACP reductase (FabI) inhibitors

Author(s):Show less -

Asse Junior, Leonardo Rander ^[1] ; Kronenberger, Thales ^[2] ; Magalhaes Serafim, Mateus Sa ^[3] ; Sousa, Yamara Viana ^[4] ; Franco, Isabella Drumond ^[1] ; Valli, Marilia ^[5] ; Bolzani, Vanderlan da Silva ^[5] ; Monteiro, Gustavo Claro ^[5] ; Bruno Prates, Joao Lucas ^[5] ; Kroon, Erna Geessien ^[3] ; Fernandes Mota, Bruno Eduardo ^[4] ; Ferreira, Diego dos Santos ^[1] ; de Oliveira, Renata Barbosa ^[1] ; Maltarollo, Vinicius Goncalves ^[1]

Affiliation

^[1] Univ Fed Minas Gerais, Fac Farma, Dept Prod Farmaceut, Av Antonio Carlos, 6627 Pampulha, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Hosp Tubingen, Dept Internal Med 8, Otfried Muller Str 14, D-72076 Tubingen - Germany

^[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Av Antonio Carlos, 6627 Pampulha, BR-31270901 Belo Horizonte, MG - Brazil

^[4] Univ Fed Minas Gerais, Fac Farm, Dept Anal Clin & Toxicol, Av Antonio Carlos, 6627 Pampulha, BR-31270901 Belo Horizonte, MG - Brazil

^[5] Univ Estadual Paulista UNESP, Inst Quim, Dept Quim Organ, Nucleo Bioensaios Biossintese & Ecofis Prod Nat N, BR-14800060 Araraquara, SP - Brazil

• Document type: Journal article
• Source: Future Medicinal Chemistry; v. 12, n. 1, p. 51-68, JAN 2020.
• Web of Science Citations: 0

Abstract

Aim: Antibiotic resistance is an alarming issue, as multidrug-resistant bacteria are growing worldwide, hence the decrease of therapeutic potential of available antibiotic arsenal. Among these bacteria, Staphylococcus aureus was pointed by the WHO in the pathogens list to be prioritized in drug development. Methods: We report the use of chemical similarity models for the virtual screening of new antibacterial with structural similarity to known inhibitors of FabI. The potential inhibitors were experimentally evaluated for antibacterial activity and membrane disrupting capabilities. Results \& conclusion: These models led to the finding of four new compounds with antibacterial activity, one of which having antimicrobial activity already reported in the literature. (AU)

• FAPESP's process: 19/05967-3 - Understanding the biological function of Natural Products' scaffolds from Databases for the design of active compounds for the treatment of infectious diseases
• Grantee: Marilia Valli
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support type: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC