Pyrazole Linked-1,2,4-Oxadiazole Derivatives as Potential Pharmacological Agent: Design, Synthesis and Antimicrobial Study

Abstract

A new series of 3-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-5-aryl-1,2,4-oxadiazole (9a–x) have been synthesized by a reaction of 5-aryl-N′-hydroxy-1-phenyl-1H-pyrazole-3-carboximidamide (7a–d) with substituted methyl benzoate (8a–f). The newly synthesized 3-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-5-aryl-1,2,4-oxadiazole (9a–x) derivatives were characterized by spectroscopic techniques and screened for in vitro antibacterial activity against Gram-positive bacterial strains Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178). Gram-negative bacterial strains Escherichia coli (NCIM 2574), it was noticed that compounds 9h, 9i, and 9j in which R = 4-Cl and R¹ = 2-Cl/4-Cl or 4-CH₃ showed good activity against B. subtilis with MIC 31.25 μg/mL against standard S. albus having MIC 7.81 μg/mL. Proteus mirabilis (NCIM 2388) and in vitro antifungal activity against Aspergillus niger (ATCC 504) Candida albicans (NCIM 3100). 3-(5-Aryl-1-phenyl-1H-pyrazol-3-yl)-5-aryl-1,2,4-oxadiazole derivatives like compound 9a (R = H, R¹ = 2-Cl), 9b (R = H, R¹ = 2-Cl), 9d (R = H, R¹ = 4-Cl), and 9k (R = 4-Cl, R¹ = 4-OCH₃) showed good activity against A. niger with MIC 31.25 µg/mL, which are comparable to standard drug ravuconazole having MIC 31.5 µg/mL. Compounds 9h (R = 4-Cl, R¹ = 2-Cl) and 9j (R = 4-Cl, R¹ = 4-CH₃) showed activity against A. niger with MIC 7.81 µg/mL which is comparable to standard drug Fluconazole having MIC 7.81 µg/mL and fourfold more activity with respect to drug Ravuconazole. The antibacterial activity of 3-(5-aryl-1-phenyl-1H-pyrazol-3-yl)-5-aryl-1,2,4-oxadiazole (9a–x) derivatives led to the conclusion that these scaffolds could aid in the creation of lead drugs to treat microbial infection.

Keywords:

• Pyrazole
• 1,2,4-oxadiazole
• antibacterial activity
• antifungal activity

Disclosure statement

No potential conflict of interest was reported by the author(s).