Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors

Gizem Erensoy; Kai Ding; Chang Guo Zhan; Ammar Elmezayen; Kemal Yelekçi; Merve Duracik; Özlem Bingöl Özakpinar; İlkay Küçükgüzel

doi:10.35333/jrp.2020.187

Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors

Gizem Erensoy
, Kai Ding
, Chang Guo Zhan
, Ammar Elmezayen
, Kemal Yelekçi
, Merve Duracik
, Özlem Bingöl Özakpinar
, İlkay Küçükgüzel

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, ¹H-/¹³C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC₅₀ of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.

Original language	English
Pages (from-to)	436-451
Number of pages	16
Journal	Journal of Research in Pharmacy
Volume	24
Issue number	4
DOIs	https://doi.org/10.35333/jrp.2020.187
State	Published - 2020

Bibliographical note

Publisher Copyright:
© 2020 Marmara University Press.

Funding

Acknowledgements: This study was supported by Marmara University Scientific Research Projects Commission under the grant no: SAG-C-DRP-081117-0616.

Funders	Funder number
Marmara University Scientific Research Projects Commission	SAG-C-DRP-081117-0616

Keywords

1,3,4-Oxadiazoles
ADME prediction
Anticancer activity
COX-1/2 inhibition
MPGES-1 inhibition
Molecular docking
Thioethers

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics
Pharmacology (medical)

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10.35333/jrp.2020.187

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title = "Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors",

abstract = "A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, 1H-/13C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-\{[2-methyl-5-(propan-2-yl)phenoxy]methyl\}-1,3,4-oxadiazol-2-yl)sulphanyl]-1(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.",

keywords = "1,3,4-Oxadiazoles, ADME prediction, Anticancer activity, COX-1/2 inhibition, MPGES-1 inhibition, Molecular docking, Thioethers",

author = "Gizem Erensoy and Kai Ding and Zhan, \{Chang Guo\} and Ammar Elmezayen and Kemal Yelek{\c c}i and Merve Duracik and \{Bing{\"o}l {\"O}zakpinar\}, {\"O}zlem and İlkay K{\"u}{\c c}{\"u}kg{\"u}zel",

note = "Publisher Copyright: {\textcopyright} 2020 Marmara University Press.",

year = "2020",

doi = "10.35333/jrp.2020.187",

language = "English",

volume = "24",

pages = "436--451",

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AU - Erensoy, Gizem

AU - Ding, Kai

AU - Zhan, Chang Guo

AU - Elmezayen, Ammar

AU - Yelekçi, Kemal

AU - Duracik, Merve

AU - Bingöl Özakpinar, Özlem

AU - Küçükgüzel, İlkay

PY - 2020

Y1 - 2020

N2 - A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, 1H-/13C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.

AB - A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, 1H-/13C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.

KW - 1,3,4-Oxadiazoles

KW - ADME prediction

KW - Anticancer activity

KW - COX-1/2 inhibition

KW - MPGES-1 inhibition

KW - Molecular docking

KW - Thioethers

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JO - Journal of Research in Pharmacy

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ER -

Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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