Designing, synthesis, and antimicrobial action of oxazoline and thiazoline derivatives of fatty acid esters
Creators: name: Ahmad, Anis
name: Ahmad, Aiman
name: Sudhakar, Raja
name: Himani Varshney
name: Naidu Subbarao
name: Ansari, Saba
name: Rauf, Abdul
name: Khan, Asad U.
Publisher: name: Taylor & Francis
Year: 2016
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: 60506 Virology

description: In this study, a novel series of oxazoline and thiazoline were designed as inhibitors of cytochrome P450 14 alpha-sterol demethylase (CYP51) from <i>Candida albicans</i> and peptide deformylase (PDF) of <i>Escherichia coli</i>. The long chain dibromo derivative of fatty acid esters on reaction with urea and thiourea gave their corresponding oxazolines and thiazolines, respectively. All the compounds were characterized by their spectral data (IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR and MS) and tested for antibacterial and antifungal activity by disk diffusion assay and minimum inhibitory concentration by the broth microdilution method against gram-positive and gram-negative strains of bacteria as well as fungus strains. The investigation into antimicrobial screening revealed that all the compounds were found to be potent antimicrobial agents. After calculating likeness drug properties of the compounds by Prediction of Activity Spectra for Substances software, ADMET-related descriptors were computed to predict the pharmacokinetic properties for the active and bioavailable compounds by discovery studio 2.5. Molecular docking studies have been performed on PDF of <i>E. coli</i> and CYP 450-14DM of <i>C. albicans</i> to understand the mode of binding of the molecules in the active site of the receptor. Compounds (2-amino-5-(carbomethoxyoctyl)-1,3-oxazoline, 2-amino-5-(carbomethoxyoctyl)-1,3-thiazoline and 2-amino-4-pentyl-5-[(8’R)-8’ hydroxy (carbomethoxydecyl)-1,3-oxazoline<b>)</b> showed excellent antimicrobial activity nearly equivalent to the control compounds and compounds, 2-amino-4-octyl-5-(carbomethoxyheptyl)-1,3-oxazolin, 2-amino-4-(2’R)(2’-hydroxy octyl)-5-(carbomethoxyheptyl)-1,3-oxazoline and 2-amino-4-pentyl-5-[(8’R)-8’-hydroxy(carbomethoxy decyl)-1,3-oxazolineshowed vasodilation and antihypertensive properties. Furthermore, a computational analysis of physicochemical parameters revealed that the most of the compounds possessed drug-like attributes. Using Bioinformatics approach, we found a correlation between the observed and predicted antimicrobial activities. A series of novel oxazoline and thiazoline derivatives of long chain unsaturated fatty acid esters were synthesized from urea and thiourea, respectively, and screened for their antibacterial activity against <i>Escherichia coli</i>, Methicillin-resistant <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, <i>Streptococcus pyogenes</i>, <i>Klebsiella pneumonia</i> and antifungal activity against <i>Candida albicans</i>, <i>Aspergillus fumigatus</i>, <i>Penicillium marneffei</i>, <i>Trichophyton mentagrophytes</i>.