Synthesis, antimicrobial activity and QSAR studies of 2,5-disubstituted benzoxazoles.
In this study, a new series of 2,5-disubstituted benzoxazoles was synthesized and their structures were elucidated by elemental analysis, MASS, (1)H-NMR, (13)C-NMR and IR spectral data. Newly and previously synthesized 2,5-disubstituted benzoxazole derivatives were evaluated for antibacterial and antifungal activity against standard strains and their drug-resistant isolates. Microbiological results showed that the compounds presented a large spectrum of activity having MIC values of 250-7.8 microg mL(-1) against the tested microorganisms. Among the newly synthesized derivatives 3-22, compound 11 was the most active against Candida krusei out of all; however, it was one dilution less potent than standard drug fluconazole. In addition, all the new and previous compounds were more active than standard drugs ampicillin trihydrate and rifampicin against Pseudomonas aeruginosa and its gentamicin-resistant isolate. The 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a set of newly and previously synthesized benzoxazoles tested for growth inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) was also performed by using multivariable regression analysis. The activity contributions for substituent effects of these compounds were determined from the correlation equation for predictions of the lead optimization.
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara University, Ankara, Turkey.
M
M
Arisoy
O
O
Temiz-Arpaci
I
I
Yildiz
F
F
Kaynak-Onurdag
E
E
Aki
I
I
Yalcin
U
U
Abbasoglu
D000667:Ampicillin / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D015195:Drug Design; D005839:Gentamicins / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology; D013057:Spectrum Analysis; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001583:Benzoxazoles; D005839:Gentamicins; D000667:Ampicillin; D012293:Rifampin