SYNTHESIS OF NOVEL 1,4,5,6,7,8-HEXAHYDROQUINOLINES OF POTENTIAL ANTIMICROBIAL ACTIVITY.

A number of 2,3-disubstituted-1-cyclohexyl 4-(3,4-dimethoxyphenyl-1,4,5,6,7,8)-hexahydroquinolines and 5-(3,4-dimethoxyphenyl-10-cyclohexyl-3,4,5,6,7,8,9,10-octahydro)-3H-pyrimido[4,5-b]quinolines were synthesized and evaluated for antimicrobial activities. Preliminary results indicated that most compounds tested in this study demonstrated considerable activity against Gram positive, Gram negative bacteria and fungi.

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF CYANOPYRIDINYL TETRAHYDRONAPHTHALENE DERIVATIVES.

A novel series of cyanopyridinyl tetrahydronaphthalene incorporated with different heterocycles were synthesized. The key compounds 2a,b were condensed with chloroacetone and ethyl chloroacetate to give 3a,b and 4a,b, respectively. Also condensation of 4a,b with hydrazine hydrate gave the corresponding hydrazide 5a,b. Reaction of 5b with different isothiocyanates gave the corresponding thiosemicarbazide derivatives 6a-c. Also, condensation of 5a with chloroacetic acid, methyl iodide and/or acetic anhydride yielded 7- 9, respectively. Moreover, reaction of 5a with acetylacetone, ethyl acetoacetate, diethylmalonate, ethyl cyanoacetate, chloroacetone, ethyl chloroacetate, urea, phthalic anhydride, malic anhydride and/ or different aldehydes yielded the corresponding derivatives 10-18, respectively. Newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium, Sarcina lutea, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli) and antifungal (Saccharomyces cerevisiae and Candida albicans) activity. The results revealed that some of novel compounds have exhibited significant biological activity against the tested microorganisms.

Synthesis, antitumor activity and molecular docking study of novel benzofuran-2-yl pyrazole pyrimidine derivatives.

A new series of (benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl) pyrimidine derivatives were synthesized from 3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-carbaldehyde (1) through different routes of cyclocondensation reactions. Condensation of 1 with active methylene compounds afforded compounds 2-8. The cyclization of 2 with chloroacetic acid, ortho substituted benzoic acid and/or ethanolamine gave compounds 9-12. Also condensation of 2 with hydrazine hydrate followed by cyclocondensation afforded corresponding triazines and pyrazole derivatives 18-27. Some docking studies of the newly prepared compounds as thymidylate synthase inhibitors have been done. Also the cytotoxic activity of some of the prepared compounds as a representative examples was evaluated against HEPG2 (human liver carcinoma cell line) in comparison with 5-fluorouracil (5-Fu).

Novel benzimidazole derivatives as expected anticancer agents.

A series of 1-(1H-benzimidazol-2-yl)-3-(substituted)-2-propen-1-one and its 1-methyl analogues 2c-h were synthesized and cyclized with different reagents such as ethyl cyanoacetate, thiourea, hydroxylamine hydrochloride, guanidinium sulfate, methylhydrazine, phenylhydrazine and/or hydrogen peroxide in different reactions to produce pyridones 3a,b, pyrimidinethione 4a,b, isoxazole 5a,b, aminopyrimidine 6a,b, pyrazoline 7i-k and epoxy derivative 8, respectively. Acetohydrazide 10 reacted with formic acid, acetic anhydride, carbon disulfide and/or thiosemicarbazide to yield compounds 11-19. Also compound 21a,b was condensed with different monosaccharides to yield the corresponding N-glycoside Schiff's bases derivatives 22a-h, which upon treatment with acetic anhydride afforded 23a-h derivatives. The anticancer activity of some of the newly synthesized compounds was evaluated against HEPG2 (human liver carcinoma cell line) and PC12 (pheochromocytoma of the rat adrenal medulla) cells. Benzimidazole-2-isoxazole 5a derivative exhibited high potency against HEPG2 and PC12 cells. Benzimidazole chalcones 2c,e, benzimidazole mercaptoacetohydrazide 14 and benzimidazole thiosemicarbazide 15a,b derivatives gave high potency against PC12 cells.