Beta
ManageSearchChatDiscover
239441

SYNTHESIS, MOLECULAR MODELING STUDY, AND BIOLOGICAL EVALUATION OF N-ACYL-ANTHRANOYLANTHRANILIC ACID DERIVATIVES AND THEIR CYCLIZED BENZOXAZINONES AS NOVEL HIV-1 NONNUCLEOSIDE REV

Article

Last updated: 04 Jan 2025

OverviewSimilar Items

Subjects

-

Tags

-

Abstract

N-Acylanthranoylanthranilic acids (5a–n)and their cyclized 4H-benzo [d][1,3] oxazin-4-one derivatives (6a–n) were prepared via a three-step process.The synthesized compoundswere then screened to determine their human immunodeficiency virus (HIV-1) nonnucleoside reverse transcriptase (NNRT) inhibition activity. The half-maximal inhibitory concentrations of the compounds, (IC50), were found to be in the range of 30 nM–123 µM, using nevirapine as a reference HIV drug. The reverse transcriptase inhibition activity of the compounds was shown to be distinctly affected by the cyclized motif and the nature of the appended N-acyl moiety. Selected active compounds, 5a, 6d, 6h, and 6k (IC50 50 / IC50 . Most of the designed compounds fulfill Lipinski's requirements of druggability. Molecular docking studies reveal H–π, H–O (N), π–π, and halogen bonding between the docked compounds and the residues within the allosteric binding pocket close to the RT active site. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO)- derived energy descriptors are shown to be useful predictive tools for reverse transcriptase inhibition (RTI) activity and in silico binding to mutant nucleophilic side chain residues in the nonnucleoside inhibitor binding pocket motif.

DOI

10.21608/bfsa.2022.239441

Keywords

NNRTIs, Anthranilamide, Benzoxazinnone, docking, SAR

Authors

First Name

Hossam.

Last Name

Abdel-Aziz

MiddleName

M.

Affiliation

Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt./ Present Affiliation, Department of Medicinal Chemistry, Faculty of Pharmacy, South Valley University, Qena, 83511, Egypt.

Email

-

City

-

Orcid

-

First Name

Ahmed

Last Name

Ali

MiddleName

M.

Affiliation

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

Email

-

City

-

Orcid

-

First Name

Atef

Last Name

Abdel-Hafez

MiddleName

A-M.

Affiliation

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

Email

-

City

-

Orcid

-

First Name

Adel

Last Name

Youssef

MiddleName

F.

Affiliation

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

Email

-

City

-

Orcid

-

Volume

45

Article Issue

1

Related Issue

34403

Issue Date

2022-06-01

Receive Date

2021-12-28

Publish Date

2022-06-01

Page Start

201

Page End

222

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 45_Issue 1_Pages 201-222.pdf

PDF . 1.2MB

Link

https://bpsa.journals.ekb.eg/article_239441.html

Detail API

https://bpsa.journals.ekb.eg/service?article_code=239441

Order

17

Type

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

SYNTHESIS, MOLECULAR MODELING STUDY, AND BIOLOGICAL EVALUATION OF N-ACYL-ANTHRANOYLANTHRANILIC ACID DERIVATIVES AND THEIR CYCLIZED BENZOXAZINONES AS NOVEL HIV-1 NONNUCLEOSIDE REV

Details

Type

Article

Created At

22 Jan 2023