Synthesis, Molecular Properties Prediction, and Anti-staphylococcal Activity of N-Acylhydrazones and New 1,3,4-Oxadiazole Derivatives

Abstract

Abstract:Five new 1-(2-(5-nitrofuran-2-yl)-5-(aryl)-1,3,4-oxadiazol-3-(2H)-yl) ethanone compounds 5a-e were synthesized by cyclization of N-acylhydrazones 4a-e with acetic anhydride under reflux conditions. Their structures were fully characterized by IR, 1 H-NMR, and 13 C-NMR. Furthermore, evaluations of the antibacterial activity of the 1,3,4-oxadiazoles 5a-e and N-acylhydrazones 4a-e showed strong activity against several strains of Staphylococcus aureus, with MICs between 4 μg/mL to 32 μg/mL. In silico studies of the parameters of Lipinski's Rule of Five, as well as the topological polar surface area (TPSA), absorption percentage (% ABS), drug likeness and drug score indicate that these compounds, especially 4a and 5d, have potential to be new drug candidates.

Synthesis and testing of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives for antifungal activity against selected Candida Species

“…The 1 H and 13 C NMR spectroscopic techniques were sufficient to confirm the formation of the 1,3,4-oxadiazoline ring because of its very characteristic signals. 2,17 For example, in the 1 H NMR spectra of compounds of the series 1 (4a-l), two typical signals were observed, one assigned to the methyl protons of the acetyl group linked to the nitrogen atom N-3 in the aliphatic region of 2.27 to 2.30 ppm, and another assigned to methinic protons H-2 in the aromatic region 7.17 to 7.63 ppm. In the 13 C NMR spectra, signals characteristic of C=O around 167 ppm, and methyl carbon atom CH 3 in the range of 20.1-22.7 ppm, as well as the oxadiazole ring signal C-2 around 88.7 to 92.9 ppm, and C-5 around 152.5 to 163.4 ppm were observed, thus confirming its formation.…”

“…The characterization of series 3 (4 r-v) compounds was recently reported by our group. 2 In the infrared spectrum, compounds 4a-q showed amide C=O absorption bands from 1662 to 1674 cm -1 , C-O-C absorption stretches (oxadiazole ring) from 1095 to 1240 cm -1 , and C=N absorptions (oxadiazole ring) from 1604 to 1635 cm -1 . The compound 4-(3-acetyl-5-(pyridin-4-yl)-2,3-dihydro-1,3,4-oxadiazol-2-yl)phenyl acetate 4l and all compounds of series 2 (4m-q) also showed absorption bands in the 1755 to 1759 cm -1 range for C=O (acetoxy group).…”

“…The N-acylhydrazone compounds (3) were obtained from a condensation reaction between acylhydrazides, and aromatic/hetero-aromatic aldehydes according to the literature. 2 The cyclization reaction of the derivatives (3) with acetic anhydride afforded 1,3,4-oxadiazoline derivatives 4a-v in yields that were moderate to good (45.4-81.2%).…”

“…It has been noted that compounds containing the 1,3,4-oxadiazoline motif generally exhibit excellent antimicrobial activity. [2][3][4][5][6][7][8][9][10][11][12] Therefore, taking into consideration our ongoing research and the importance of the 1,3,4-oxadiazoline scaffold as a good source for the discovery of new and biologically active molecules, our group synthesized new 1,3,4-oxadiazoline heterocyclic compounds, (specifically 3-acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles), and pre-screened these compounds for candidacy as novel antifungal agents.…”

“…Compounds of series 3 (4r-v) were recently reported by our research group. 2 The purity of the compounds was verified examining their melting ranges and by gas chromatography (GC-MS) ( Table 1). Interestingly, all the compounds contain an acetyl group (which is polar) in the 3-position of the 1,3,4-oxadiazoline core, which gives to these compounds an intermolecular hydrogen bonding site with bio-macromolecules.…”