In vitro 5-LOX inhibitory and antioxidant potential of isoxazole derivatives

5-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 compound 3 caused concentration dependent inhibition of 5-LOX with overall IC50 value of 8.47 μM. The investigated compounds C5 also exhibited good 5-LOX inhibitory effect. The IC50 demonstrated for C5 was 10.48. Among the 10 synthesized compounds, the potential 5-LOX inhibitory effect was reported for C6. The most potent compound which showed excellent free radical scavenging effect was C3 having IC50 value of 10.96 μM. The next most potent antioxidant activity was reported for C5 which non-significantly showed free radical scavenging effect. The IC50 value observed for C5 was 13.12 μM. Compound C6 also showed potent dose dependent antioxidant effect with IC50 value 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, C6 was found most potent which showed significant 5-LOX percent inhibition assay and also reported the minimum IC50 value comparable to the reference drug. The in vitro 5-LOX enzymes inhibition assays of C5 and C3 also showed excellent percent inhibition and good potency next to C6. We concluded that amongst the investigated designed molecules the C3 was found best potent and showed significant dose dependent antioxidant activity against DPPH screening. The IC50 value reported for C3 was found good as compared to standard drug. Moreover, C5 and C6 also showed excellent free radical scavenging effect against DPPH assay. Computational methods have also been employed to explore the probable interaction model of inhibitors and enzyme active sites, and also to correlate the results of in silico and in vitro studies.