<abstract xmlns="http://www.w3.org/1999/xhtml">To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4-substituted)-<italic>N</italic>-(quinolin-3-yl) acrylamide derivatives <bold>2–24</bold>, chromenes <bold>25, 26</bold> and benzochromenes <bold>27, 28</bold> were synthesized. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, 1H NMR and 13C NMR spectroscopies. In addition, the structure of compound <bold>1</bold> was confirmed through X-ray crystallography. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. The corresponding 2-cyano-3-(4-hydroxy-3-methoxyphenyl)-<italic>N</italic>-(quinolin-3-yl) acrylamide (<bold>15</bold>), 3-oxo-<italic>N</italic>-(quinolin-3-yl)-3<italic>H</italic>-benzol[<italic>f</italic>] chromene-2-carboxamide (<bold>27</bold>), 2-cyano-3-(4-fluorophenyl-<italic>N</italic>-(quinolin-3-yl) acrylamide (<bold>7</bold>), 2-cyano-5-(4-(dimethyl-amino) phenyl)-<italic>N</italic>-(quinolin-3-yl) penta-2,4-dienamide (<bold>19</bold>) exhibited higher activity compared to doxorubicin (with <italic>IC</italic>50 value of 47.9 μmol L−1) as a reference drug, with <italic>IC</italic>50 values of 29.8, 39.0, 40.0, 40.4 μmol L−1, resp. Also, quinoline acrylamides containing 2,3,4-trimethoxyphenyl <bold>17</bold>, 2-chlorophenyl <bold>10</bold>, benzo[<italic>d</italic>][1,3]dioxol <bold>12</bold>, 2-methoxynaphthalen <bold>22</bold>, 2,4-dichlorophenyl <bold>18</bold> and quinoline carrying a chromene-3-carboxamide moiety <bold>25</bold> were nearly as active as doxorubicin, while quinoline acrylamides incorporating unsubstituted phenyl <bold>2</bold>, <italic>p</italic>-tolyl <bold>3</bold>, 2,4-dienamide <bold>8</bold>, 3-nitrophenyl <bold>13</bold>, 4-nitrophenyl <bold>14</bold>, 3,4-dimethoxyphenyl <bold>16</bold> and chromene <bold>26</bold> exhibited a moderate activity. In addition, quinoline with acetamide <bold>1</bold>, 4-hydroxyphenyl <bold>4</bold>, 4-dimethylaminophenyl <bold>9</bold>, 4-chlorophenyl <bold>11</bold>, 3-bromophenyl <bold>20</bold>, 4-bromophenyl <bold>21</bold> and 3-thienyl moiety <bold>24</bold> showed less activity than doxorubicin. On the other hand, quinoline having 2-methoxyphenyl <bold>5</bold>, 4-methoxyphenyl <bold>6</bold>, 4-metho xynaphthalene <bold>23</bold> and chromene-2-carboxamide <bold>28</bold> showed no activity.</abstract>

To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4-substituted)-N-(quinolin-3-yl) acrylamide derivatives 2–24, chromenes 25, 26 and benzochromenes 27, 28 were synthesized. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, 1H NMR and 13C NMR spectroscopies. In addition, the structure of compound 1 was confirmed through X-ray crystallography. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. The corresponding 2-cyano-3-(4-hydroxy-3-methoxyphenyl)-N-(quinolin-3-yl) acrylamide (15), 3-oxo-N-(quinolin-3-yl)-3H-benzol[f] chromene-2-carboxamide (27), 2-cyano-3-(4-fluorophenyl-N-(quinolin-3-yl) acrylamide (7), 2-cyano-5-(4-(dimethyl-amino) phenyl)-N-(quinolin-3-yl) penta-2,4-dienamide (19) exhibited higher activity compared to doxorubicin (with IC50 value of 47.9 μmol L−1) as a reference drug, with IC50 values of 29.8, 39.0, 40.0, 40.4 μmol L−1, resp. Also, quinoline acrylamides containing 2,3,4-trimethoxyphenyl 17, 2-chlorophenyl 10, benzo[d][1,3]dioxol 12, 2-methoxynaphthalen 22, 2,4-dichlorophenyl 18 and quinoline carrying a chromene-3-carboxamide moiety 25 were nearly as active as doxorubicin, while quinoline acrylamides incorporating unsubstituted phenyl 2, p-tolyl 3, 2,4-dienamide 8, 3-nitrophenyl 13, 4-nitrophenyl 14, 3,4-dimethoxyphenyl 16 and chromene 26 exhibited a moderate activity. In addition, quinoline with acetamide 1, 4-hydroxyphenyl 4, 4-dimethylaminophenyl 9, 4-chlorophenyl 11, 3-bromophenyl 20, 4-bromophenyl 21 and 3-thienyl moiety 24 showed less activity than doxorubicin. On the other hand, quinoline having 2-methoxyphenyl 5, 4-methoxyphenyl 6, 4-metho xynaphthalene 23 and chromene-2-carboxamide 28 showed no activity.

Anti-breast cancer activity of some novel quinoline derivatives

Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"Anti-breast cancer activity of some novel quinoline derivatives"}

To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4-substituted)-N-(quinolin-3-yl) acrylamide derivatives 2–24, chromenes 25, 26 and...

Anti-breast cancer activity of some novel quinoline derivatives

Publicado en línea: 30 sept 2015

Páginas: 271 - 283

Aceptado: 01 jul 2015

DOI: https://doi.org/10.1515/acph-2015-0030

Palabras clave
quinolineacrylamides, chromenes, benzochromenes, anti-breast cancer activity

© Mostafa M. Ghorab et al.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Anti-breast cancer activity of some novel quinoline derivatives

Publicado en línea: 30 sept 2015

Páginas: 271 - 283

Aceptado: 01 jul 2015

DOI: https://doi.org/10.1515/acph-2015-0030

Palabras clavequinolineacrylamides, chromenes, benzochromenes, anti-breast cancer activity

© Mostafa M. Ghorab et al.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Palabras clave
quinolineacrylamides, chromenes, benzochromenes, anti-breast cancer activity