2,4-CYCLOADDITION REACTIONS: PREPARATION AND CYTOTOXICITY OF NOVEL QUINOLINE AND PYRROLO [3,4-f] QUINOLINE DERIVATIVES

Objective: the present work aimed to synthesize novel quinoline and pyrroloquinoline derivatives and study their cytotoxic activity.Methods: Diels–Alder reaction (4+2) was used for the synthesis of new quinolone and pyrrolo quinoline derivatives via the reactions of compound 1 with N-maleimide (4a-d) derivatives, ethyl acrylate (6) methylmethacrylate (8) and acetylene dicarboxylic acid (10). The synthesized compounds were characterized by NMR and Mass spectral data. Some of the synthesized compounds were screened for their antitumor activity against three different cell lines (MCF-7, HepG2 and HCT).Results: The tested compounds exhibited antiproliferative activity against the three different cell lines, especially against MCF-7.Conclusion: New quinoline and pyrroloquinoline derivatives were synthesized starting with 6-methyl-4-phenyl-2-thioxo-5-(4-methylphenylthio)-1,2-dihydropyridine-3-carbonitrile. Two new compounds 3 and 5a were tested for their in vitro antiproliferative activity against MCF-7, HepG2 and HCT cancer cell lines. The result showed that compound 3 exhibited more potent antiproliferative activity than compound 5a in case of MCF-7 and HCT cell lines.Â

Facile synthesis and characterization of novel pyrido[3′,2′:4,5]thieno[3,2-<i>d</i>]pyrimidin-4(3<i>H</i>)-one and pyrido[2′,3′:3,4]pyrazolo[1,5-<i>a</i>]pyrimidine incorporating 1,3-diarylpyrazole moiety

<p>4-(3-(4-Hydroxyphenyl)-1-phenyl-1<i>H</i>-pyrazol-4-yl)-6-phenyl-2-thioxo-1,2-di hydro-pyridine-3-carbonitrile (<b>1</b>) reacted with ethyl chloroacetate (<b>2</b>) in ethanolic sodium acetate solution to yield the corresponding ethyl (3-cyanopyridin-2-ylsulphanyl)acetate derivative <b>3</b>. Intramolecular cyclization of compound <b>3</b> was achieved by its heating in DMF containing potassium carbonate to afford the corresponding ethyl 3-aminothieno[2,3-<i>b</i>]pyridine-2-carboxylate derivative <b>4</b> which reacted with hydrazine hydrate in refluxing pyridine to yield the starting material 3-aminothieno[2,3-<i>b</i>]pyridine-2-carbohydrazide derivative <b>7</b>. Compound <b>7</b> reacted with different reagents such as triethylorthoformate, formic acid, acetic acid and acetic anhydride to afford the target molecules pyrido[3′,2′:4,5]thieno[3,2-<i>d</i>]pyrimidin-4(3<i>H</i>)-one derivatives <b>8–10</b>, <b>12</b> and <b>13</b> in good to excellent yields. On the other hand, pyridine-2(1<i>H</i>)-thione derivative <b>1</b> reacted with hydrazine hydrate in refluxing pyridine to give the other starting material 3-amino-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridine derivative <b>20</b> which reacted with acetylacetone under reflux to afford the target molecule pyrido[2′,3′:3,4]pyrazolo[1,5-<i>a</i>]-pyrimidine derivative <b>21</b> in a good yield. The structures of target molecules were elucidated using elemental analyses and spectral data.</p