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

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

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 synthesiz...

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Main Authors: Rashmin khanam, Iram I. Hejazi, Syed Shahabuddin, Abdul R. Bhat, Fareeda Athar
Format: Article
Language:English
Published: Elsevier 2019-04-01
Series:Journal of Pharmaceutical Analysis
Online Access:http://www.sciencedirect.com/science/article/pii/S2095177918305082
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spelling doaj-b164d29073e04ef0a22970eeb73101b42021-04-02T14:59:56ZengElsevierJournal of Pharmaceutical Analysis2095-17792019-04-0192133141Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitorsRashmin khanam0Iram I. Hejazi1Syed Shahabuddin2Abdul R. Bhat3Fareeda Athar4Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, IndiaResearch Centre for Nano-Materials and Energy Technology (RCNMET), School of Science and Technology, Sunway University, 47500 Selangor, MalaysiaDepartment of Chemistry, Sri Pratap College, Cluster University, Srinagar 190001, IndiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India; Corresponding author.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. Keywords: 1, 3, 4-oxadiazoles, Structure-activity relationship (SAR), Antioxidant activities, STAT3 inhibitors, Molecular dockinghttp://www.sciencedirect.com/science/article/pii/S2095177918305082
collection DOAJ
language English
format Article
sources DOAJ
author Rashmin khanam
Iram I. Hejazi
Syed Shahabuddin
Abdul R. Bhat
Fareeda Athar
spellingShingle Rashmin khanam
Iram I. Hejazi
Syed Shahabuddin
Abdul R. Bhat
Fareeda Athar
Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors
Journal of Pharmaceutical Analysis
author_facet Rashmin khanam
Iram I. Hejazi
Syed Shahabuddin
Abdul R. Bhat
Fareeda Athar
author_sort Rashmin khanam
title Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors
title_short Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors
title_full Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors
title_fullStr Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors
title_full_unstemmed Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors
title_sort pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and stat3 inhibitors
publisher Elsevier
series Journal of Pharmaceutical Analysis
issn 2095-1779
publishDate 2019-04-01
description 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. Keywords: 1, 3, 4-oxadiazoles, Structure-activity relationship (SAR), Antioxidant activities, STAT3 inhibitors, Molecular docking
url http://www.sciencedirect.com/science/article/pii/S2095177918305082
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