title: Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives.
abstract: 1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7-11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12-15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18-21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated that compounds 8 and 16 showed the best results, exhibiting the highest inhibitory effects towards the three tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic towards normal cells (IC50 values > 100 μg/mL).
authors.affiliation: Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Monawarah 1343, Saudi Arabia. emanmflefel@yahoo.com.|Department of Photochemistry, National Research Centre, Dokki, Cairo 12622, Egypt. emanmflefel@yahoo.com.
authors.forename: Eman
authors.initials: E
authors.lastname: M Flefel
authors.affiliation: Department of Photochemistry, National Research Centre, Dokki, Cairo 12622, Egypt. hebatallah201528@yahoo.com.|Department of Chemistry, College of Science, King Khalid University, Abha 9004, Saudi Arabia. hebatallah201528@yahoo.com.
authors.forename: Hebat-Allah
authors.initials: HA
authors.lastname: S Abbas
authors.affiliation: Department of Photochemistry, National Research Centre, Dokki, Cairo 12622, Egypt. randaabdelmagid@yahoo.com.
authors.forename: Randa
authors.initials: R
authors.lastname: E Abdel Mageid
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt. wzaghary@yahoo.com.
authors.forename: Wafaa
authors.initials: W
authors.lastname: A Zaghary
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D004095:Dihydropyridines; D004317:Doxorubicin
keywords: 4-fluorophenylpyridine; acetohydrazide; chloropyridine; cytotoxicity; nicotinonitrile