الفهرس 
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Abstract
Synthesis of Novel Multi-heterocyclic Compounds of Expected Biological Activities from Several Functional Pyranoquinolinones
A series of monobromo-pyrano[3,2-c]quinoline-2,5-diones 2a-c were synthesized via reaction of pyranoquinolinones 1a-c with phosphorus pentabromide under free solvent reaction conditions at 100oC.
Bromination of 3-nitropyrano[3,2-c]quinoline-2,5-diones 3a-c using phosphorus pentabromide under free solvent condition produced dibromo pyrano[3,2c]quinolinediones 4a-c.
3-Amino-4-bromopyrano[3,2-c]quinolinediones 6a-c were obtained via reaction of 3-aminopyrano[3,2-c]quinoline-2,5-diones 5a-c with phosphorus pentabromide at 100oC.
The newly synthesized compounds were tested for their antitumor activity against several cancer cell lines A-549 (human lung cancer), HCT-116 (human colon cancer), MCF-7 (breast cancer), and HePG-2 (human liver cancer). The inhibitory activity of the synthesized compounds was compared with 5-fluorouracil (positive reference drug). The cytotoxic activity results showed that most of the cited compounds exhibited significant inhibitory affects all tested cell lines. Notably, the target compound 4c, containing two bromine atoms on pyrano moiety, was the most potent antitumor agent toward four tumor cell lines compared with the positive reference drug (5-fluoro uracil). The presence of the alkyl group (R) effects on antitumor activity. As N-alkyl chain length increases, the antiproliferative activity toward tumor cell lines increases. Also, the insertion of the electron-withdrawing group (Br) and the electron-donating group (NH2) enhanced the inhibitory activity. The presence of an amino group at position 3 with bromine group at position 4 in pyranoquinolinone moiety enhanced the cytotoxicity of the synthesized compounds.
Besides, the existence of two bromine atoms at positions 3 and 4 on pyrano moiety played a vital role in increasing inhibition activity.
Treatment of N-ethyl-3-nitro pyranoquinolinone 3b with hydrazine hydrate using absolute ethanol as a solvent under reflux produced pyrazolylquinolinone derivative 7 which was reduced by concentrated HCl and tin to afford the corresponding amino derivative 8. Compound 8 condensed with some different aldehydes in presence of acetic acid to give the target Schiff bases.
Reaction of N-ethyl-3-nitro pyranoquinolinone 3b with phosphorus oxychloride in the presence of triethylamine gave N-ethyl-4-chloro-3-nitropyrano quinolindione 12. The latter compound 12 was stirred in ethanol with hydrazine hydrate to afford 4-hydrazinyl-3-nitro pyranoquinolinone 13. Compound 13 was reacted with some aldehydes in the presence of glacial acetic acid to get the desired hydrazinyl pyranoquinolinone derivatives 14-16.
Antiproliferative activity of two series of the obtained Schiff bases and hydrazone derivatives was estimated toward three tumor cell lines A-549 (human lung cancer), HCT-116 (human colon cancer), and MCF-7 (breast cancer). The inhibition effects of the synthesized compounds were compared with 5-fluorouracil as a chemotherapeutic drug. Insertion of chlorine atom improved the inhibition activity as in compound 11 which showed good anticancer activity toward A-549 and HCT116 cell lines. Also, existence of nitro group enhances anticancer activity as in compound 15 has high cytotoxic activity than compounds 14, 16 compared to standard drug.