Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives

Molecules

Eman M. Flefel³  Hebat-Allah S. Abbas²  Randa E. Abdel Mageid²  Wafaa A. Zaghary¹  Derek J. McPhee⁴ 

[1] Department of Pharmaceutical Chemistry, College of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt;Department of Photochemistry, National Research Centre, Dokki, Cairo 12622, Egypt;Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Monawarah 1343, Saudi Arabia;;Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Monawarah 1343, Saudi Arabia

关键词: nicotinonitrile;    4-fluorophenylpyridine;    acetohydrazide;    chloropyridine;    cytotoxicity;   

DOI  :  10.3390/molecules21010030

来源: mdpi

【 摘 要 】

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).

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.