الفهرس 
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Abstract
PART I:Synthesis And Biological Evaluation Of Some Novel Fused Pyrazolo Heterocyclic Rings Incorporating A Benzothiazole Ring System: Due to diverse biological importance of benzothiazole and pyrazole heterocyclic rings, we aim in this work to synthesize a new series of heterocyclic compounds bearing pyrazole nucleus linked to benzothiazole nucleus and to assess their anti-carcinogenic effects against hepatocellular carcinoma (liver) HePG-2, mammary gland (breast) MCF-7, Human (prostate) cancer cell line PC3 and Colorectal carcinoma (colon) HCT-116. Thus, reflux of 2-hydrazinylbenzo[d]thiazole (1) with acetyl acetone for long time afforded 2-(3,5-dimethyl-1H-pyrazol-1-yl)benzo[d]thiazole (2). 1-(1,3-Benzothiazol-2-yl)-3- methyl-1,4-dihydro-5H-pyrazol-5-one (4) was prepared by the treatment of compound 1 with ethyl acetoacetate (3) in boiling acetic acid or in boiling ethanolic potassium hydroxide. The condensation between(4) with two heterocyclic aldehydes such as furfural (5a) and isonicotinaldehyde(5b), furnished the corresponding title compounds 2-(benzo[d]thiazol-2-yl)-4-(furan-2-ylmethylene)-5-methyl-2,4-dihydro-3H-pyrazol-3-one (6a) and 2-(benzo[d]thiazol-2-yl)-5-methyl-4-(pyridin-4-ylmethylene)-2,4-dihydro-3H-pyrazol-3-one (6b).Compounds 6a, b were used a versatile material for synthesis of fused pyrazolo heterocyclic rings, thus on treatment 6a, b with hydrazine hydrate in boiling dimethylformamide in case of 6a or in boiling ethanol for 6b, it afforded 2-(4-(furan-2-yl)-3-methyl-5,6-dihydropyrazolo[3,4-c]pyrazol-1(4H)-yl)benzo[d]thiazole (9a) and 2-(4-(4-pyridyl)-3-methyl-5,6-dihydropyrazolo[3,4-c]pyrazol-1(4H)-yl)benzo[d]thiazole (9b) respectively.In a similar manner, pyrazolo[4,3-d]isoxazole derivatives were synthesized on treatment 6a, b with hydroxylamine hydrochloride in presence of a catalytic amount of piperdine, it afforded 6-(benzo[d]thiazol-2-yl)-3-(furan-2-yl)-4-methyl-3,6-dihydro-2H-pyrazolo[4,3-d]isoxazole (12a) and 6-(benzo[d]thiazol-2-yl)-3-(pyridin-4-yl)-4-methyl-3,6-dihydro-2H-pyrazolo[4,3-d]isoxazole (12b).A pyrano[2,3-c]pyrazole derivatives were synthesized by reaction of 6a, b with ketonic compounds. Thus reaction of 6a, b with cyclopentanone or cyclohexanone 13a, b in refluxing dimethylformamide containing a catalytic amount of piperidine, it afforded 14a-d.Also, pyrano[2,3-c]pyrazole derivatives were synthesized by reaction of 6a, b with keto active methylene compounds such as acetylacetone (15a) and ethyl acetoacetate (15b) in boiling dimethylformamide containing a catalytic amount of piperidine. The reaction gave the corresponding compounds 18a-d.Similar treatment of compounds 6a, b with a compounds possessing active methylene nitrile groups such as malononnitrile and /or ethyl cyanoacetate (19a, b) in refluxing dimethylformamide under basic conditions afforded the pyrano[2,3-c]pyrazole derivatives 23a-d.On treatment of 6a, b with cyanoacetamide in refluxing dimethylformamide (6a) or refluxing ethanol (6b) , it behave different behavior and it gave 1-(benzo[d]thiazol-2-yl)-3-methyl-6-oxo-4-aryl-6,7-dihydro-1H-pyrazolo [3,4-b]pyridine-5-carbonitrile derivatives (25a, b) instead of pyranopyrazole derivatives (24a, b).On treatment 6a, b with cyanoacetohydrazide (26) in refluxing dimethylformamide containing a catalytic amount of piperdine of afforded7-(benzo[d]thiazol-2-yl)-5-methyl-4-aryl-1,4,7,8-tetrahydrodipyrazolo[3,4-b:4’,3’-e]pyridin-3(2H)-one (27a, b).Substituted 1-(benzo[d]thiazol-2-yl)- 3-methyl-4-aryl-1,4-dihydropyrazolo[3,4-d][1,3]thiazine )31a-d (was synthesized from the reaction of 6a, b with thioamide derivatives 28a, b in boiling dimethylformamide containing a catalytic amount of triethylamine or piperidine afforded the Michael adduct 29. Nucleophilic addition of imino group to carbonyl group led to formation of intermediate 30, which underwent dehydration to form compounds 31a-d.On reaction of 6a, b with guandine nitrate in refluxing dimethylformamide containing a catalytic amount of piperdine afforded 1-(benzo[d]thiazol-2-yl)-3-methyl-4-aryl-1H-pyrazolo[3,4-d]pyrimidin-6-amine (35a, b).PART II:Synthesis Of Novel Acetohydrazides And Sulphonamides Containing Benzothiazole Moiety: In conjunction with acetohydrazide as important functionality and a key precursors for the synthesis of several bioactive heterocyclic compounds.In the present work we wish to report a simple synthesis of N’-(benzo[d]thiazol-2-yl)-2-((4-aryl)amino)acetohydrazide derivatives (39a-c), (41) and (43a,b), thus on treatment of 1 with chloroacetyl chloride )36( in chloroform as solvent containing a catalytic amount of potassium carbonate afforded N’-(benzo[d]thiazol-2-yl)-2-chloroacetohydrazide (37).On boiling 37 with different aryl amines 38a-c in dimethylformamide containing a catalytic amount of triethylamine for 14-16 hours afforded the corresponding compounds 39a-c.Thus, on refluxing 37 with benzenesulphonamides (40) in dimethylformamide containing a catalytic amount of triethylamine for long time afforded (41).Also, refluxing 37 with some sulpha drugs 42a, b afforded the benzenesulphonamide 43a, b .PART III: Biological Evaluation Of New Synthized Compounds:1-Antioxidant activity: It can be suggested that all compounds except 2, 6a, 12a, 14a, 14d, 18d, 23b, 25b, 31b, 31c, 35a and 35b exhibit moderate to very strong antioxidant activity. The compounds 6b, 9b, 12b, 18b, 23a, 27a and 31d gave very strong antioxidant activity. Compounds 9b and 6b displayed the best antioxidant property (88.23%) and (87.84%) respectively even more than the standard L-Ascorbic acid (87.45%).2-Cytotoxic Screening:The In vitro cytotoxicity IC50 (µmol/L) of the newly synthesized compounds were studied using the 5-fluorouracil as reference drug, including HePG-2 (liver), MCF-7 (breast), PC3 (prostate) and HCT-116 (colon).All compounds showed cytotoxicity against HePG2, PC3, HCT-116and MCF-7 except compounds 2, 6a, 25b and 31c have not any activity against HePG2, PC3, HCT-116 and MCF-7.Compounds 6b and 9b showed cytotoxicity more than 5-FU except showed very strong against MCF-7 and PC3 respectively, even compound 12b showed cytotoxicity more strong than standard drug 5-FU against HePG2 but showed very strong for other test. The compound 18a is has very strong cytotoxicity towards the four cell lines, while compound 27a is very strong cytotoxicity against HePG2 and MCF-7, but is has strong cytotoxicity against HCT-116and PC3, while compounds 23a and 31d are have strong cytotoxicity towards the cell lines except have very strong cytotoxicity against HCT-116 and MCF-7, respectively.