RESUMEN
Libraries of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 1-14/15-28/29-42 and 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 43-48/49-54/55-60 were synthesized and their stereochemistry was established by 1D/2D NMR spectral and single crystal XRD studies. All the synthesized oximes and oxime ethers were screened for their in vitro antimicrobial activity against a panel of pathogenic bacteria (Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa) and fungi (Candida albicans, Candida parapsilosis, Aspergillus niger and Cryptococcus neoformans) using Gentamicin and Fluconazole as standards, respectively. From the SAR profile, the lead molecules were identified.
Asunto(s)
Antiinfecciosos/síntesis química , Compuestos de Azabiciclo/síntesis química , Éteres/química , Oximas/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Compuestos de Azabiciclo/química , Compuestos de Azabiciclo/farmacología , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Bibliotecas de Moléculas Pequeñas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Two series of bicyclic oxime ethers viz, 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one O-benzyloximes 13-24 and 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one O-benzyloximes 31-36 were synthesized and stereochemistry was established by their spectral (1D and 2D NMR) and crystal studies. Synthesized oxime ethers were screened for their in vitro antimicrobial activity against a set of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, Escherichia coli and Klebsiella pneumoniae) and fungi (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger and Aspergillus flavus) by twofold serial dilution method, respectively, using Ciprofloxacin and Amphotericin B as standards. Most of the molecules expressed promising antimicrobial profile against the tested pathogens and even a few compounds 16, 21, 22, 33 and 34 were better than standard drugs.
Asunto(s)
Antibacterianos/química , Antifúngicos/química , Compuestos Bicíclicos con Puentes/química , Éteres/química , Oximas/química , Antibacterianos/síntesis química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Compuestos Bicíclicos con Puentes/síntesis química , Compuestos Bicíclicos con Puentes/farmacología , Éteres/síntesis química , Éteres/farmacología , Hongos/efectos de los fármacos , Oximas/síntesis química , Oximas/farmacologíaRESUMEN
Three series of oxime ethers viz, 2,6-diarylpiperidin-4-one O-benzyloximes 5a-o, 2,6-diaryltetrahydropyran-4-one O-benzyloximes 7a-e and 2,6-diaryltetrahydrothiopyran-4-one O-benzyloximes 11a-b and 12a-c were synthesized and stereochemistry is established by their spectral and single crystal analysis. A SAR study has been carried out for the above oxime ethers against a panel of antibacterial (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi and Escherichia coli) and antifungal agents (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger, Aspergillus flavus and Cryptococcus neoformans), respectively, using Ciprofloxacin and Amphotericin B as standards. Most of the chloro/methyl/methoxy substituted compounds exerted moderate to good activity against all the tested organisms; moreover, some compounds (5i, 5l, 5n, 5o, 7c2, 7d1, 7d2, 7e, 11b and 12c) exhibited promising activity than standard drugs.