Synthesis and Biological Evaluation of Some Pyridine Derivatives as Antimicrobial Agents

Abstract

In this study, several pyridine derivatives were synthesized and evaluated for their in vitro antimicrobial activity against Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Aspergillus niger and Candida albicans). The intermediate chalcone derivatives 2a,b were synthesized by condensation of pyrazole aldehydes 1a,b with acetophenone in alcoholic KOH. Cylization of 2a,b with ethyl cyanoacetate and ammonium acetate resulted in pyridine carbonitrile derivatives 3a,b. Furthermore, condensation of pyridine-4-carboxaldeyde, 4 with different amino-derivatives gave rise to pyridine derivatives 5a,b, 6a,b. The oxadiazole derivative 7a was prepared by cylization of 6a with acetic anhydride. Characterization of the synthesized compound was performed using IR, 1H NMR, 13C NMR spectra and elemental microanalyses. The antimicrobial test results revealed that compounds 5a, 6b and 7a (MIC = 50 μg/ml) exhibited half fold antibacterial activity compared to ampicillin (MIC = 25 μg/ml), against B. cereus. On the other hand, compound 3b (MIC = 25 μg/ml) showed an equivalent activity compared to miconazole (MIC = 25 μg/ml) against C. albicans and to clotrimazole (MIC = 100 μg/ml) against the clinical isolate C. albicans 6647. Moreover, this compound was further tested for its acute toxicity profile. The results showed that its oral and parentral LD50s are more than 300 mg/kg and 100 mg/kg, respectively. Therefore, compound 3b is a good candidate as antifungal agent with good acute toxicity profile, and deserves more investigation to find out its mechanism of action and bioavailability.

Keywords: synthesis, pyridine derivatives, in vitro antibacterial, antifungal, acute toxicity