SPECIFIC BRAIN DELIVERY OF PYRIDYL CHLOROETHYLUREA DERIVATIVES AS POTENTIAL ANTITUMOR AGENTS: SYNTHESIS, EVALUATION AND MOLECULAR MODELING STUDY - Egyptian Knowledge Bank

147026

SPECIFIC BRAIN DELIVERY OF PYRIDYL CHLOROETHYLUREA DERIVATIVES AS POTENTIAL ANTITUMOR AGENTS: SYNTHESIS, EVALUATION AND MOLECULAR MODELING STUDY

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Last updated: 25 Dec 2024

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Abstract

The present investigation describes the synthesis; evaluation and molecular modeling studies of a series of 1-substituted-1,4-dihydropyridine-3-chloroethylurea derivatives IIIa-e as potential agents for treatment of brain tumors. The incorporation of the 1,4-dihydropyridine moiety in the structure attains an efficient site specific chemical delivery system (CDS) of the chloroethylurea (CEU) as a known antitumor pharmacophore to the brain. The target compounds IIIa-e were synthesized through reduction of the corresponding quaternary compounds IIa-e. The in-vitro oxidation studies showed that, compounds IIIa-e could be oxidized into their corresponding quaternary compounds IIa-e, respectively which attains their “locked in" characteristics as brain antitumor agents. The in-vivo studies showed that compound IIIa was able to cross the BBB at detectable concentration. In addition the in-vitro alkylating activity studies using 4-(4-nitrobenzyl)pyridine (NBP) revealed that compound IIe is an efficient alkylating agent with activity comparable to reference drug chlorambucil. The target compounds were tested for their binding to the colchicine-binding site (CBS) of b-tubulin using Molecular Operating Environment (MOE) software.

DOI

10.21608/bfsa.2010.147026

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First Name

Nawal

Last Name

A. El-Koussi

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Affiliation

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

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9726

Issue Date

2010-06-01

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2010-03-13

Publish Date

2010-06-30

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Print ISSN

1110-0052

Online ISSN

3009-7703

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BFSA_Volume 33_Issue 1_Pages 69-78.pdf

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https://bpsa.journals.ekb.eg/article_147026.html

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Bulletin of Pharmaceutical Sciences Assiut University

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

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