Design, synthesis and biological evaluation of some novel substituted quinazolines as antitumor agents

Amer M Alanazi; Alaa A-M Abdel-Aziz; Ibrahim A Al-Suwaidan; Sami G Abdel-Hamide; Taghreed Z Shawer; Adel S El-Azab

doi:10.1016/j.ejmech.2014.04.029

Design, synthesis and biological evaluation of some novel substituted quinazolines as antitumor agents

Eur J Med Chem. 2014 May 22:79:446-54. doi: 10.1016/j.ejmech.2014.04.029. Epub 2014 Apr 12.

Authors

Amer M Alanazi¹, Alaa A-M Abdel-Aziz², Ibrahim A Al-Suwaidan¹, Sami G Abdel-Hamide³, Taghreed Z Shawer⁴, Adel S El-Azab⁵

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, Alkharj, Saudi Arabia.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
⁵ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt. Electronic address: adelazaba@yahoo.com.

PMID: 24763265
DOI: 10.1016/j.ejmech.2014.04.029

Abstract

A novel series of 6-chloro-2-p-tolylquinazolinone and substituted-(4-methylbenzamido)benzamide (1-20) were designed, synthesized and evaluated for their in-vitro antitumor activity. Compounds 3, 14 and 16 possessed remarkable broad-spectrum antitumor activity. Compound 16 was found to be a particularly active growth inhibitor of the renal cancer (GI50 = 4.07 μM), CNS cancer (GI50 = 7.41 μM), ovarian cancer (GI50 = 7.41 μM) and non-small cell lung cancer (GI50 = 7.94 μM). Compound 16 ranks as nearly 1.5-fold more potent (mean GI50 = 15.8 μM) compared to 5-FU (mean GI50 = 22.6 μM).

Keywords: In-vitro antitumor evaluation; NCI; Quinazoline; Selective activity; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclization
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Quinazolines / chemical synthesis
Quinazolines / chemistry
Quinazolines / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Quinazolines