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DESIGN, SYNTHESIS AND ANTIDEPRESSANT ACTIVITY OF SOME N2-SUBSTITUTED NALIDIXIC ACID HYDRAZIDES AND THEIR CYCLIZED ANALOGUES

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Last updated: 04 Jan 2025

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Abstract

A series of N2-substituted nalidixic acid hydrazides 7-26 and some of their rigid analogues 29-31 in which the hydrazinocarbonyl moiety has been replaced by the corresponding 1,3,4-oxadiazole nucleus were synthesized as potential antidepressant agents. The preparation of the aforementioned compounds was achieved by reaction of nalidixic acid hydrazine 6 with the appropriate carbonyl compound or isothiocyanate derivative to afford the corresponding N-alkylidenes 7-11; N-arylidenes 12-26 or the thiocarbamoylhydrazinocarbonyl derivatives 27 and 28 respectively. Cyclodesulfurization of the latter derivatives yielded the corresponding 5-substituted amino-1,3,4-oxadiazoles 29 and 30. the unsubstituted 5-amino-1,3,4-oxadiazol-2-yl derivative 31 was synthesized by interaction of the hydrazide 6 with cyanogens bromide. The structures of the synthesized compounds were confirmed by IR; 1H-NMR and MS and their purity as assessed by TLC and elemental analyses. Eleven of the synthesized compounds and isocarboxazide as a reference drug were tested at three dose levels (0.5; 1.0 and 1.5 mg/kg) for antidepressant activity in mice. Reduction in the duration of immobility in forced swimming test was taken as a measure for antidepressant activity. Seven of the tested substituted compounds and the unsubstituted hydrazide 6 exhibited highly significant difference from the control group at a dose level of 1.5 mg/kg. The acetophenonylidene derivative 18 showed antidepressant activity comparable to that of the reference drug. The rigid substituted hydrazide analogues represented by compound 29 were found to be inactive at the lower dose level and showed moderately significant difference than the control group at the higher dose level. This indicates that, cyclization of the hydrazide moiety to the corresponding 1,3,4-oxadiazole derivatives greatly reduced the antidepressant activity.

DOI

10.21608/bfsa.1998.67767

Authors

First Name

Adel

Last Name

Youssef

MiddleName

F.

Affiliation

Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

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Orcid

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First Name

Farghaly

Last Name

Omar

MiddleName

A.

Affiliation

Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

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City

-

Orcid

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First Name

Hosney

Last Name

Elsherief

MiddleName

A.

Affiliation

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt

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Orcid

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First Name

Gamal El Din

Last Name

Abuo-Rahma

MiddleName

A. A.

Affiliation

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt

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Orcid

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Volume

21

Article Issue

1

Related Issue

10245

Issue Date

1998-06-01

Receive Date

1997-12-01

Publish Date

1998-06-30

Page Start

15

Page End

26

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 21_Issue 1_Pages 15-26.pdf

PDF . 653.1kB

Link

https://bpsa.journals.ekb.eg/article_67767.html

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https://bpsa.journals.ekb.eg/service?article_code=67767

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Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

DESIGN, SYNTHESIS AND ANTIDEPRESSANT ACTIVITY OF SOME N2-SUBSTITUTED NALIDIXIC ACID HYDRAZIDES AND THEIR CYCLIZED ANALOGUES

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Article

Created At

22 Jan 2023