Development of certain novel N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)-benzamides and 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones as CFM-1 analogs: design, synthesis, QSAR analysis and anticancer activity

Ahmed M Alafeefy; Abdelkader E Ashour; Onkar Prasad; Leena Sinha; Shilendra Pathak; Fatimah A Alasmari; Arun K Rishi; Hatem A Abdel-Aziz

doi:10.1016/j.ejmech.2014.12.048

Development of certain novel N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)-benzamides and 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones as CFM-1 analogs: design, synthesis, QSAR analysis and anticancer activity

Eur J Med Chem. 2015 Mar 6:92:191-201. doi: 10.1016/j.ejmech.2014.12.048. Epub 2014 Dec 27.

Authors

Ahmed M Alafeefy¹, Abdelkader E Ashour², Onkar Prasad³, Leena Sinha³, Shilendra Pathak³, Fatimah A Alasmari⁴, Arun K Rishi⁵, Hatem A Abdel-Aziz⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Salman Bin Abdulaziz University, P.O. Box 173, Alkharj, 11942, Saudi Arabia. Electronic address: a.alafeefy@sau.edu.sa.
² Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
³ Department of Physics, University of Lucknow, 226007, Lucknow, India.
⁴ Department of Chemistry, College of Science, King Saud University, PO Box 22955, Riyadh, 11416, Saudi Arabia.
⁵ John D. Dingell VA Medical Center, Wayne State University, Detroit, MI, USA; Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; Department of Oncology, Wayne State University, Detroit, MI, USA.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, 12622, Egypt. Electronic address: hatem_741@yahoo.com.

PMID: 25555142
DOI: 10.1016/j.ejmech.2014.12.048

Abstract

The reaction of N-(2-(hydrazinecarbonyl)aryl)benzamides 2a, b with indoline-2,3-diones 4ae in acidified ethanolic solution furnished the corresponding N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)benzamides 5aj, respectively. Furthermore, 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones 6aj were prepared by the reaction of 3-amino-2-arylquinazolin-4(3H)-one 3a, b with 4ae. Six derivatives of the twenty newly synthesized compounds showed remarkable antitumor activity against most of the tested cell lines, Daoy, UW228-2, Huh-7, Hela and MDA-MB231. Although these six compounds were more potent than the standard drug (CFM-1), indeed compounds 5b, 5d and 6b were the best candidates with IC50 values in the range 1.866.87, 4.4210.89 and 1.468.60 μg/ml and percentage inhibition in the range 77.188.7, 59.4184.8 and 75.488.0%, respectively. QSAR analyses on the current series of derivatives also have been performed for all five cancer cell lines and thus 10 statistically significant models were developed and internally cross validated.

Keywords: 2-oxoindolin-3-ylidene; Anticancer agents; CFM analogues; Hydrazones; Quinazoline.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Benzamides / chemical synthesis
Benzamides / chemistry
Benzamides / pharmacology*
Benzodiazepinones / chemical synthesis
Benzodiazepinones / chemistry
Benzodiazepinones / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
HeLa Cells
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Molecular Structure
Quantitative Structure-Activity Relationship*
Quinazolinones / chemical synthesis
Quinazolinones / chemistry
Quinazolinones / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzamides
Benzodiazepinones
CFM 1
Indoles
N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)-benzamide
Quinazolinones