Acta Pharm. 60 (2010) 311-323
Original research paper
Design and synthesis of novel
thiophenecarbohydrazide, thienopyrazole and thienopyrimidine derivatives as
antioxidant and antitumor agents
AMEEN ALI ABU-HASHEM, MOHAMED
FATHY EL-SHEHRY and FARID ABD-ELRAHEEM BADRIA
1 Photochemistry Department (Heterocyclic Unit),
National Research Center, 12622 Dokki,
Giza, Egypt
2 Green Chemistry Department ,National Research
Center, 12622 Dokki,
Giza, Egypt
3 Department of Pharmacognosy, Faculty of Pharmacy, Mansoura
University, 35516 Mansoura, Egypt
Accepted July 16, 2010
2-Amino-5-acetyl-4-methyl-thiophene-3-carboxylic acid ethyl ester (1) and 5-acetyl-2-amino-4-methylthiophene-3-carbohydrazide (2) were synthesized and used as starting materials for the synthesis of new series of 1-(5-amino-4-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3a), 1-(5-amino-4-(4-chloro-3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3b), 1-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) pyrazolidine-3,5-dione (4), (Z)-N'-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) formohydrazonic acid (5a), (Z)-ethyl-N'-(4-methyl-2-amino-5-acetylthiophene-3-carbonylformo hydrazonate (5b), 6-acetyl-3-amino-2,5-dimethylthieno[2,3-d]pyrimidin-4(3H)-one (8), 5-methyl-3-amino-2-mercapto-6-acetylthieno[2,3-d]pyrimidin-4(3H)-one (10) and 5-methyl-6-acetyl-2-thioxo-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-one (12) as potential antioxidant and antitumor agents. Pharmacological results showed that compounds 6a, 6b, 8, 10 and 12 exhibited promising antitumor and antioxidant activity.
Keywords: thienopyrazole, thieno[2,3-d]pyrimidines, thiophenecarbohydrazide, antioxidant activity, bleomycin-dependent DNA damage, antitumor activity