Pharmacokinetic evaluation molecular docking and in vitro biological evaluation of 1 3 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

摘要

1, 3, 4-Oxadiazole derivatives >(4a–5f) were previously synthesized to investigate their anticancer properties. However, studies relating to their antioxidant potential and signal transducer and activator of transcription (STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives (>4a–5f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical (DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound >5e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound >5e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound >5e (-9.91kcal/mol). Through virtual screening, compound >5e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound >5e decreased the activation of STAT3 as observed with Western blot. In brief, compound >5e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.