Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives
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 ph...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/21/1/30 |
| _version_ | 1818346773357264896 |
|---|---|
| author | Eman M. Flefel Hebat-Allah S. Abbas Randa E. Abdel Mageid Wafaa A. Zaghary |
| author_facet | Eman M. Flefel Hebat-Allah S. Abbas Randa E. Abdel Mageid Wafaa A. Zaghary |
| author_sort | Eman M. Flefel |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-12-13T17:23:36Z |
| format | Article |
| id | doaj.art-61da1b6027d64496b6cdbf86285214db |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T17:23:36Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-61da1b6027d64496b6cdbf86285214db2022-12-21T23:37:15ZengMDPI AGMolecules1420-30492015-12-012113010.3390/molecules21010030molecules21010030Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile DerivativesEman M. Flefel0Hebat-Allah S. Abbas1Randa E. Abdel Mageid2Wafaa A. Zaghary3Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Monawarah 1343, Saudi ArabiaDepartment of Photochemistry, National Research Centre, Dokki, Cairo 12622, EgyptDepartment of Photochemistry, National Research Centre, Dokki, Cairo 12622, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt1-(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).http://www.mdpi.com/1420-3049/21/1/30nicotinonitrile4-fluorophenylpyridineacetohydrazidechloropyridinecytotoxicity |
| spellingShingle | Eman M. Flefel Hebat-Allah S. Abbas Randa E. Abdel Mageid Wafaa A. Zaghary Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives Molecules nicotinonitrile 4-fluorophenylpyridine acetohydrazide chloropyridine cytotoxicity |
| title | Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives |
| title_full | Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives |
| title_fullStr | Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives |
| title_full_unstemmed | Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives |
| title_short | Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives |
| title_sort | synthesis and cytotoxic effect of some novel 1 2 dihydropyridin 3 carbonitrile and nicotinonitrile derivatives |
| topic | nicotinonitrile 4-fluorophenylpyridine acetohydrazide chloropyridine cytotoxicity |
| url | http://www.mdpi.com/1420-3049/21/1/30 |
| work_keys_str_mv | AT emanmflefel synthesisandcytotoxiceffectofsomenovel12dihydropyridin3carbonitrileandnicotinonitrilederivatives AT hebatallahsabbas synthesisandcytotoxiceffectofsomenovel12dihydropyridin3carbonitrileandnicotinonitrilederivatives AT randaeabdelmageid synthesisandcytotoxiceffectofsomenovel12dihydropyridin3carbonitrileandnicotinonitrilederivatives AT wafaaazaghary synthesisandcytotoxiceffectofsomenovel12dihydropyridin3carbonitrileandnicotinonitrilederivatives |