Antimicrobial activity of some celastroloids and their derivatives

Author(s)

Inacio, Marielle Cascaes ; Paz, Tiago Antunes ; Wijeratne, E. M. Kithsiri ; Gunaherath, G. M. Kamal B. ; Guido, Rafael V. C. ; Gunatilaka, A. A. Leslie

• Document type: Journal article
• Source: MEDICINAL CHEMISTRY RESEARCH; v. 31, n. 9, p. 12-pg., 2022-07-13.

Abstract

Infections are among the 10 deadliest diseases in the world. Here we screened 19 celastroloids and their derivatives 1-19 against several strains of bacteria and yeast of biomedical significance. In general, quinonemethide-type celastroloids, except isoiguesterin (8) exhibited significant antibacterial activity for Staphylococcus aureus ATCC 25923, MRSA ATCC 33592, and the clinical isolate STA6 with MICs of 0.39-12.50 mu g/mL, whereas 14(15)-enequinonemethide, balaenol (12), showed antifungal activity against Candida albicans ATCC 10261 with an MIC of 3.12 mu g/mL. Among the phenolic triterpenes and their derivatives, zeylasterone (14) had an MIC of 1.56 mu g/mL for all 3 strains of S. aureus, and zeylasteral (15) was active against C. albicans at 3.12 mu g/mL. Cytotoxicity assays revealed that most quinonemethides were cytotoxic with IC(50)s of 0.16-0.36 mu g/mL that are below their MIC values. However, 14(15)-enequinonemethide 12 and phenolic triterpenes 14 and 15 exhibited antimicrobial activity at sub-cytotoxic concentrations, suggesting that these celastroloids are potential candidates for further studies. Molecular docking studies were used to investigate the theoretical affinities for potential protein targets of 12 and 14 in S. aureus, and 15 in C. albicans. Based on their docking scores, it can be inferred that 12 and 14 inhibits GyrB in S. aureus, and 15 inhibits Bdfl in C. albicans. [GRAPHICS] . (AU)

• FAPESP's process: 20/12904-5 - Discovery of Plasmodium falciparum inhibitors from Cerrado plants as lead compounds candidates for malaria: integrated studies of ultra-efficient chromatography, spectroscopy, and biological assays
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 14/19362-2 - Application of biotechnology to evaluate plant-microorganism interaction during production of secondary metabolites in Peritassa campestris and its endophytes
• Grantee: Marielle Cascaes Inácio
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/00143-0 - Fungal biotransformation of quinonemethide triterpenes and their (new) structure-activity relationship on tumor cell lines
• Grantee: Marielle Cascaes Inácio
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC