title: Designing, synthesis, and antimicrobial action of oxazoline and thiazoline derivatives of fatty acid esters.
abstract: In this study, a novel series of oxazoline and thiazoline were designed as inhibitors of cytochrome P450 14 alpha-sterol demethylase (CYP51) from Candida albicans and peptide deformylase (PDF) of Escherichia coli. 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,1H NMR,13C 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 E. coli and CYP 450-14DM of C. albicans 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) 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.
authors: a Medical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202 002 , India.
authors: Anis
authors: A
authors: Ahmad
authors: b Department of Chemistry , Aligarh Muslim University , Aligarh 202 002 , India.
authors: Aiman
authors: A
authors: Ahmad
authors: c School of Computational and Integrative Sciences, Jawaharlal Nehru University , New Delhi , India.
authors: Raja
authors: R
authors: Sudhakar
authors: b Department of Chemistry , Aligarh Muslim University , Aligarh 202 002 , India.
authors: Himani
authors: H
authors: Varshney
authors: c School of Computational and Integrative Sciences, Jawaharlal Nehru University , New Delhi , India.
authors: Naidu
authors: N
authors: Subbarao
authors: d Department of Radiation Oncology , Miller School of Medicine/Sylvester Comprehensive Cancer Center, University of Miami , Miami , FL 33136 , USA.
authors: Saba
authors: S
authors: Ansari
authors: b Department of Chemistry , Aligarh Muslim University , Aligarh 202 002 , India.
authors: Abdul
authors: A
authors: Rauf
authors: a Medical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202 002 , India.
authors: Asad U
authors: AU
authors: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D052978:Disk Diffusion Antimicrobial Tests; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D007711:Klebsiella pneumoniae / Q000187:drug effects; D062105:Molecular Docking Simulation; D010080:Oxazoles / Q000737:chemistry* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004952:Esters; D010080:Oxazoles; D013844:Thiazoles
keywords: antimicrobial agent; docking; drug resistance; oxazoline; thiazoline