IN VITRO5-LOX INHIBITORY POTENTIAL AND ANTIOXIDANT ACTIVITY OF NEW ISOXAZOLE DERIVATIVES

Abstract

ABSTRACT5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors are highly attractive. In this research the previously synthesized isoxazole derivatives has been investigated against 5-Lox inhibitory and antioxidant in vitro assay. The percent inhibition forC3were 89.93±1.73, 85.94±0.91, 81.90±1.32, 77.51±0.59 and 74.80±1.41 at various concentrations with IC50of 8.47 µM. The investigated compoundsC5also exhibited good 5-LOX inhibitory effect. The non-significant percent inhibition forC5were demonstrated as 91.30±1.42, 87.78±0.45, 84.44±0.86, 79.72±1.89 and 75.29±1.64 at various concentration (1000-62.5 µg/ml). The IC50demonstrated forC5was 10.48. Among the 10 synthesized compounds, the potential 5-LOX inhibitory effect was reported forC6. The most potent compound which showed excellent free radical scavenging effect wasC3with different percent inhibitions of 92.51±0.62, 87.65±0.70, 82.25±0.55, 79.37±0.69 and 75.72±0.51 having IC50value of 10.96 µM. The next most potent antioxidant activity was reported forC5which non-significantly showed free radical scavenging effect. The DPPH percent inhibition reported forC5was 92.63±0.64, 88.45±0.55, 83.53±0.41, 79.42±0.46 and 76.10±0.64 at different ranges of (1000, 500, 250, 125 and 62.5 µg/mL) concentrations, respectively. The IC50value observed forC5was 13.12 µM. CompoundC6also showed potent dose dependent antioxidant effect with IC50value of 18.87 µM having percent inhibition of 91.63±0.55, 88.45±0.49, 83.53±0.45, 78.42±0.66 and 73.72±0.64 at concentration 1000-62.5 µg/mL respectively.Among the tested compounds,C6was found most potent which showed significant 5-LOX percent inhibition assay and also reported the minimum IC50value comparable to the reference drug. Thein vitro5-Lox enzymes inhibition assays ofC5andC3also showed non-significant percent inhibition and good potency next toC6. We concluded that amongst the investigated designed molecules theC3was found best potent and showed significant dose dependent antioxidant activity against DPPH screening. The IC50value reported forC3was found good as compared to standard drug. Moreover,C5andC6also showed excellent free radical scavenging effect against DPPH assay.