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

Publication date: Available online 7 December 2018Source: Journal of Pharmaceutical AnalysisAuthor(s): Rashmin khanam, Iram I. Hejazi, Syed Shahabuddin, Abdul R. Bhat, Fareeda AtharAbstract1, 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, 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 SH-2 domain of STAT3 was the highest for compound 5e(-9.91 kcal/mol). Through virtual screening, compound 5ewas found to exhibit optimum competency in inhibiting STAT3 activity. Compound5e decreased t...
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research