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Synthesis and Antibacterial Activity of Novel Semi‐Synthetic Triterpenoids
Author(s) -
Da Silva Gabriela Jorge,
Pereira Manuela,
Da Salvador Jorge
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.777.20
Subject(s) - enterococcus faecalis , antibacterial activity , antimicrobial , ursolic acid , staphylococcus aureus , bacteria , microbiology and biotechnology , chemistry , minimum inhibitory concentration , escherichia coli , biological activity , pseudomonas aeruginosa , broth microdilution , biology , biochemistry , in vitro , chromatography , gene , genetics
Emergence of antimicrobial resistance has become a critical public health concern worldwide. Novel antimicrobials are urgently needed, and plants with therapeutic properties constitute a rich source of biologically active compounds. Triterpenoids are a class of compounds found widely distributed in nature and have shown diverse biological activity, including anti‐tumoral activity. Structure‐activity studies have revealed that alterations in key carbons may enhance biological activity and reduce cytotoxicity. Little is known of the antibacterial activity of olealonic (OA) and ursolic (UA) acids. Moreover, the antibacterial activity of modified triterpene pentacyclic structures has yet to be characterized. AIM The objective of this study was to synthesize derivatives of olealonic (OA) and ursolic (UA) acids, and to test them against the antibiotic susceptible Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 strains, and methicillin‐resistant S. aureus and vancomycin‐resistant E. faecalis of clinical origin. METHODS and RESULTS Initially, OA, UA, and 14 semi‐synthetic derivatives were screened for antibacterial activity by the disk diffusion method. Minimum inhibitory concentrations (MIC) were determined by microdilution method. MICs ranged from 62.5 to 125 ug/mL in Gram negative bacteria, from 31.3 to 125 ug/mL for S. aureus strains and from 7.8 to 125 ug/mL for E. faecalis . In general, UA and compound 14, a derivative of UA, showed the best activity against Gram positive bacteria. No significant differences in MICs were observed between the antibiotic susceptible and resistant clinical strains. Both compounds reduced the bacterial growth of S. aureus ATCC 29213 and E. faecalis ATCC 29212 in the presence of 0,5xMIC, MIC, 2xMIC relatively to the control, more significant in the latter. MTT cytotoxicity assays revealed that compound 14 did not induce significant cell toxicity in macrophages (RAW 264.7), with 84% viability at concentrations delivering effective (MIC). Overall, the compounds tested showed a better antimicrobial activity against Gram‐positive bacteria. CONCLUSION The data indicate that compound 14 may offer a new avenue for the development of new antimicrobials with reduced cytotoxicity. This work also illustrates that modifications of the natural molecule and the study of structure‐activity relationship is crucial to unravel new biological activity.