XX Simposio de Investigaciones en Salud 2018, XX Simposio de investigaciones en salud "Enfermedades Crónicas No Transmisibles"

Por defecto: 
Biological evaluation of novel synthetic heterocyclic compounds against resistant bacteria.
Maria del Pilar Crespo Ortiz, Rodrigo Abonia Gonzalez, Braulio Insuasty Obando, Jairo Quiroga Puello

Última modificación: 2018-09-05


The biological activities conferred by structural modifications of synthetic heterocyclic compounds have been explored for designing novel therapeutic agents.The aim of this work was to identify leading molecules in a library of novel heterocyclics and its derivatives of easy and simple synthesis at low cost. Methods: A total of 570 compounds including series of quinolines, chalcones, pyridines, sulfonamides, pyrazolines, prolines, isobenzofuranones and indazole-derivatives were designed and synthesized. The compounds were assessed for antibacterial activity against wild type and multidrug resistant gram-negative and gram-positive bacteria including E. coli ATCC25922, methicillin-susceptible S.aureus ATCC25923 (MSSA), methicillin-resistant S.aureus ATCC43300 (MRSA), vancomycin-intermediate S.aureus(VISA), carbapenemase+ K. pneumoniae BAA1705, K. pneumoniae ATCC700603 (ESBL+), P. aeruginosa ATCC27853 and N. gonorrhoeae ATCC 31426 (beta lactamase+). Minimal inhibitory concentrations(MIC) were determined in those compounds with reproducible antimicrobial effects. For N.gonorrhoeae agar microdilution was performed. Results: The pyridine and pyrazoline derivatives were the most active compounds of the library particularly against MSSA, MRSA and N. gonorrhoeae: the substituted fluorophenylpyridine chalcone (MICs MRSA 2μg/mL, MSSA 16µg/mL) and the phenylpyridine chalcone (MICs MRSA 16µg/mL, MSSA 31.25µg/mL). One pirazole indolin-derivative was selectively active against VISA (MIC 3.9μg/mL) other pyrazole  was active against MRSA (MIC 3.9μg/mL) and N. gonorrhoeae 2.9μg/mL. E. coli was inhibited by two pyridine derivatives (MIC 7.8-15μg/mL).Three proline derivatives inhibited N. gonorrhoeae growth (MIC 3.9μg/mL). Conclusions: The compounds exhibited greater activity against S. aureus and little or no growth inhibition of gram-negative bacteria. The most biologically active compounds were the 4-chloro-substituted chalcones two of them having effects on VISA.