TY - JOUR
T1 - Physicochemical interpretation, with qsar/sar analysis, of how the barriers of pseudomonas aeruginosa bacteria were penetrated by parasubstituted n-arylbenzylimines
T2 - Synthesis, characterization, and in vitro antibacterial effect
AU - Quintana-Zavala, Delia
AU - Morán-Díaz, Jessica Rubí
AU - Ávila-Melo, José Luis
AU - Gómez-Pliego, Raquel
AU - Jiménez-Vázquez, Hugo Alejandro
AU - Trujillo-Ferrara, José Guadalupe
AU - Guevarasalazar, Juan Alberto
N1 - Publisher Copyright:
©2021, Sociedad Química de México.
PY - 2021
Y1 - 2021
N2 - Resistance to antibiotics is a growing problem that imposes limitations on current therapy around the world. The World Health Organization (WHO) recommends creating new antibacterial molecules to inhibit the most harmful bacteria by aiming at specific targets. Among such bacteria is multi-drug resistant Pseudomonas aeruginosa, a Gram-negative bacterium responsible for 70% of invasive infections worldwide. The aim of this investigation was to synthesize N-arylbenzylimines, examine their antibacterial activity against P. aeruginosa ATCC 27853, and determine their physicochemical properties by quantitative structure-activity relationship (QSAR/SAR) analysis. Seven N-arylbenzylimines were synthesized with yields ≥50%, all with the Econfiguration (as shown by NMR spectra and confirmed with X-ray diffraction). The in vitro microbiological evaluations were carried out with the Kirby-Bauer method, following the guidelines of the Clinical & Laboratory Standards Institute (CLSI). The N-arylbenzylimines produced a very good antibacterial effect on P. aeruginosa, with minimum inhibitory concentration (MIC) values ranging from 198.47-790.10 µM, calculated by the Hill method. Based on the slopes of the concentration-response curves, the mechanism of action is different between the test compounds and aztreonam, the reference drug. The QSAR study performed with in vitro experimental data found that biological activity correlates most significantly with molecular size, followed by lipophilicity and electronic effects. According to the SAR analysis of antibacterial activity, molecules cross bacterial barriers differently if they bear substituents with resonance versus inductive electronic effects. The physicochemical data presently described are of utmost importance for designing and developing new molecules to combat the pathogenicity and resistance of P. aeruginosa.
AB - Resistance to antibiotics is a growing problem that imposes limitations on current therapy around the world. The World Health Organization (WHO) recommends creating new antibacterial molecules to inhibit the most harmful bacteria by aiming at specific targets. Among such bacteria is multi-drug resistant Pseudomonas aeruginosa, a Gram-negative bacterium responsible for 70% of invasive infections worldwide. The aim of this investigation was to synthesize N-arylbenzylimines, examine their antibacterial activity against P. aeruginosa ATCC 27853, and determine their physicochemical properties by quantitative structure-activity relationship (QSAR/SAR) analysis. Seven N-arylbenzylimines were synthesized with yields ≥50%, all with the Econfiguration (as shown by NMR spectra and confirmed with X-ray diffraction). The in vitro microbiological evaluations were carried out with the Kirby-Bauer method, following the guidelines of the Clinical & Laboratory Standards Institute (CLSI). The N-arylbenzylimines produced a very good antibacterial effect on P. aeruginosa, with minimum inhibitory concentration (MIC) values ranging from 198.47-790.10 µM, calculated by the Hill method. Based on the slopes of the concentration-response curves, the mechanism of action is different between the test compounds and aztreonam, the reference drug. The QSAR study performed with in vitro experimental data found that biological activity correlates most significantly with molecular size, followed by lipophilicity and electronic effects. According to the SAR analysis of antibacterial activity, molecules cross bacterial barriers differently if they bear substituents with resonance versus inductive electronic effects. The physicochemical data presently described are of utmost importance for designing and developing new molecules to combat the pathogenicity and resistance of P. aeruginosa.
KW - Antibacterial activity
KW - E-configuration
KW - Electronic effects
KW - Partition coefficient
KW - QSAR/SAR
UR - http://www.scopus.com/inward/record.url?scp=85110424820&partnerID=8YFLogxK
U2 - 10.29356/jmcs.v65i3.1481
DO - 10.29356/jmcs.v65i3.1481
M3 - Artículo
AN - SCOPUS:85110424820
SN - 1870-249X
VL - 65
SP - 376
EP - 395
JO - Journal of the Mexican Chemical Society
JF - Journal of the Mexican Chemical Society
IS - 3
ER -