title: 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.
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.
authors.affiliation: 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.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Alafeefy
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Abdelkader E
authors.initials: AE
authors.lastname: Ashour
authors.affiliation: Department of Physics, University of Lucknow, 226007, Lucknow, India.
authors.forename: Onkar
authors.initials: O
authors.lastname: Prasad
authors.affiliation: Department of Physics, University of Lucknow, 226007, Lucknow, India.
authors.forename: Leena
authors.initials: L
authors.lastname: Sinha
authors.affiliation: Department of Physics, University of Lucknow, 226007, Lucknow, India.
authors.forename: Shilendra
authors.initials: S
authors.lastname: Pathak
authors.affiliation: Department of Chemistry, College of Science, King Saud University, PO Box 22955, Riyadh, 11416, Saudi Arabia.
authors.forename: Fatimah A
authors.initials: FA
authors.lastname: Alasmari
authors.affiliation: 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.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Rishi
authors.affiliation: 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.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D001570:Benzodiazepinones; C119032:CFM 1; D007211:Indoles; C000602698:N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)-benzamide; D052999:Quinazolinones
keywords: 2-oxoindolin-3-ylidene; Anticancer agents; CFM analogues; Hydrazones; Quinazoline