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Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

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Volume 60, Issue 3 (Sep 2010)

Issues

Design and synthesis of novel thiophenecarbohydrazide, thienopyrazole and thienopyrimidine derivatives as antioxidant and antitumor agents

Ameen Abu-Hashem
  • Photochemistry Department (Heterocyclic Unit), National Research Center, 12622 Dokki Giza, Egypt
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mohamed El-Shehry / Farid Badria
Published Online: 2010-12-06 | DOI: https://doi.org/10.2478/v10007-010-0027-6

Design and synthesis of novel thiophenecarbohydrazide, thienopyrazole and thienopyrimidine derivatives as antioxidant and antitumor agents

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 tests showed that compounds 6a, 6b, 8, 10 and 12 exhibited significant antitumor and antioxidant activity.

Dizajniranje i sinteza novih derivata tiofenkarbohidrazida, tienopirazola i tienopirimidina s antioksidativnim i antitumorskim djelovanjem

Etilni ester 2-amino-5-acetil-4-metil-tiofen-3-karboksilne kiseline (1) i 5-acetil-2-amino-4-metiltiofen-3-karbohidrazid (2) sintetizirani su i upotrebljeni kao reaktanti u sintezi novih spojeva 1-(5-amino-4-(3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3a), 1-(5-amino-4-(4-klor-3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3b), 1-(4-metil-2-amino-5-acetiltiofen-3-karbonil) pirazolidin-3,5-diona (4), (Z)-N'-(4-metil-2-amino-5-acetiltiofen-3-karbonil) formohidrazonske kiseline (5a), (Z)-etil-N'-(4-metil-2-amino-5-acetiltiofen-3-karbonilformo hidrazonata (5b), 6-acetil-3-amino-2,5-dimetiltieno.2,3-d.pirimidin-4(3H)-one (8), 5-metil-3-amino-2-merkapto-6-acetiltieno.2,3-d.pirimidin-4(3H)-ona (10) i 5-metil-6-acetil-2-tiokso-2,3-dihidrotieno.2,3-d.pirimidin-4(1H)-ona (12) kao potencijalnih antioksidansa i citostatika. Farmakološka ispitivanja ukazuju na to da spojevi 6a, 6b, 8, 10 i 12 imaju značajno antitumorsko i antioksidativno djelovanje.

Keywords: thienopyrazole; thieno[2,3-d]pyrimidines; thiophenecarbohydrazide; antioxidant activity; bleomycin-dependent DNA damage; antitumor activity

Keywords: tienopirazol; tieno[2,3-d]pirimidini; tiofenkarbohidrazid; antioksidativno djelovanje; bleomicin-ovisno DNA oštećenje; antitumorsko djelovanje

  • K. Dore, S. Dubus, H. A. Ho, I. Levesque, M. Brunette, G. Corbeil, M. Boissinot, G. Boivin, M. Bergeron, D. Boudreau and M. Leclerc, Fluorescent polymeric transducers for the rapid, simple and specific detection of nucleic acids at the zeptomole level, J. Am. Chem. Soc. 126 (2004) 263-287.Google Scholar

  • R. L. Jarvest, I. L. Pinto, S. M. Ashman, C. E. Dabrowski, A.V. Fernandez, L. J. Jennings, P. Lavery and D. G. Taw, Inhibition of herpes proteases and antiviral activity of 2-substituted thieno[2,3-d]oxazinones, Bioog. Med. Chem. Lett. 9 (1999) 443-448.CrossrefGoogle Scholar

  • L. Aurelio, H. Figler, L. B. Flynn, J. Linden and J. P. Scammells, 5-Substituted 2-aminothiophenes as A1 adenosine receptor allosteric enhancers, J. Bioorg. Med. Chem. 16 (2008) 1319-1328; DOI: 10.1016/J.BMC.Web of ScienceGoogle Scholar

  • H. Lütjens, A. Zickgraf, H. Figler, J. Linden, R. Olsson and J. P. Scammells, 2-Aminothienopy-ridazines as novel adenosine A1 receptor allosteric modulators and antagonists, J. Med. Chem. 46 (2003) 1870-1877.Google Scholar

  • K. A. Ghakraborti, B. Gopalakrishnan, M. E. Sobhia and A. Malde, Three D-QSAR studies on thieno [3,2-d] pyrimidines as phosphodiesterase IV inhibitors, Bioorg. Med. Chem. Lett. 13 (2003) 1403-1408.CrossrefGoogle Scholar

  • G. Nikolakopoulos, H. Figler, J. Linden and P. J. Scammells, 2-Aminothiophene-3-carboxylates and carboxamides as adenosine A1 receptor allosteric enhancers, Bioorg. Med. Chem. 14 (2006) 2358-2365; DOI: 10.1016/j.bmc.2005.11.018.CrossrefGoogle Scholar

  • S. Sasaki, N. Cho, Y. Nara, M. Harada, S. Endo, N. Suzuki, Sh. Furuya and M. Fujino, Discovery of a thieno [2,3-d] pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: a highly potent and orally bioavailable non-peptide antagonist for the human utilizing hormone-releasing hormone receptor, J. Med. Chem. 46 (2003) 113-124.CrossrefGoogle Scholar

  • M. O. Nassan, Y. A. Hassan, I. H. Heiba and M. M. Ghorb, Synthesis and reactions of some mercaptoheterocyclic compounds and their radioprotection, Al-Azhar Bull. Sci. 8 (1997) 435-444; ref. Chem. Abstr. 130 (1999) 110174.Google Scholar

  • I. H. Heiba, M. M. Ghorab, E. N. Amin and L. Ramadan, Synthesis of 2-[(5,6,7,8-tetrahydrobenzo [b] thieno[2,3-d]pyrimidin-4-y)thio]-N-(4-aryl-3-chloro-2-oxoazetidin-1-yl) acetamides and biochemical screening for radioprotective character, Egypt. J. Biotechnol. 4 (1998) 16-30; ref. Chem. Abstr. 132 (2000) 49937.Google Scholar

  • H. N. Hafez and A. B. A. El-Gazzar, Design and synthesis of 3-pyrazolyl-thiophene, thieno [2,3-d] pyrimidines as new bioactive and pharmacological activities, Bioorg. Med. Chem. Lett. 18 (2008) 5222-5227; DOI: 10.1016/j.bmcl.2008.08.071.CrossrefGoogle Scholar

  • A. Rosowsky, K. K. N. Chen and M. Lin, 2,4-Diaminothieno [2,3-d] pyrimidines as antifolates and antimalarials, J. Med. Chem. 16 (1973) 191-194.CrossrefGoogle Scholar

  • F. Shuichi and S. Nobuhiro, Preventives/Remedies for Alzheimer's Disease, Japan Pat. 01 78, 780 (Cl. A61K45/00), 25 Oct 2001, JP Appl. 2000/112, 046, 13 Apr 2000; ref. Chem. Abstr. 135 (2001) 313627w.Google Scholar

  • I. Hirotsune, K. Takashi, N. Eisuke, K. Hidetaka, O. Masamichi, T. Takashi and N. Atsushi, Preparation of thienopyrimidine derivatives as antagonists of metabotropic glutamate receptors, Japan Pat. 02 62,803 (Cl. C07D495/04) 15 Aug 2002, Appl. 2001/32, 121; ref. Chem. Abstr. 137 (2002) 169542m.Google Scholar

  • W. Lichen, R. Jinzhi, L. Baolin, L. Jiaxuan and Y. Jing, Synthesis and cardiac activity of thieno [3,4-d] pyrimidine-2,4-dione derivatives, Journal of Zhongguo Yaoke Daxue Xuebao 29 (1998) 331-335; ref. Chem. Abstr. 130 (1999) 139309d.Google Scholar

  • T. H. Brown, R. J. Ife and C. A. Leach, Preparation and formulation of thienopyrimidine derivatives as antiulcer agents, Eur. Pat. 404356 (Cl.C07D495/0; ref. Chem. Abstr. 115 (1991) 356-361.Google Scholar

  • A. B. A. El-Gazzar, R. A. H. Hussein and N. H. Hafez, Synthesis of 4-substituted pyrido[2,3-d] pyrimidin-4(1H)-one as analgesic and anti-inflammatory agents, Acta Pharm. 57 (2007) 395-411; DOI: 10.2478/v10007-007-0032-6.CrossrefGoogle Scholar

  • Y. Morimoto, K. Tanaka, Y. Iwakiri, S. Tokuhiro, S. Fukushima and Y. Takeuchi Erythrocyte hemolysis was mediated by peroxyl radicals in this assay system, Biol. Pharm. Bull. 18 (1995) 1417-1422.CrossrefGoogle Scholar

  • E. Lissi, B. Modak, R. Torres, J. Escobar and A. Urzua, Total antioxidant potential of resinous exudates from Heliotropium species, and a comparison of the ABTS and DPPH methods, Free Radical. Res. 30 (1999) 471-477.Google Scholar

  • A. B. A. El-Gazzar, H. N. Hafez, A. A. Abu-Hashem and A. S. Aly, Synthesis and antioxidant, anti-inflammatory, and analgesic activity of novel polycyclic pyrimido[4,5-b]quinolines, Phosphorus Sulfur 184 (2009) 379-405; DOI: 10.1080/10426500802167027.CrossrefWeb of ScienceGoogle Scholar

  • A. B. A. El-Gazzar, A. M. S. Youssef, M. M. Youssef, A. A. Abu-Hashem and F. A. Badria, Design and synthesis of azolopyrimidoquinolines, pyrimidoquinazolines as anti-oxidant, anti-inflammatory and analgesic activities, Eur. J. Med. Chem. 44 (2009) 609-624; DOI: 10.1016/j. ejmech.2008.03.022.CrossrefGoogle Scholar

  • R. Aeschlach, J. Loliger, C. B. Scott, A. Murcia, J. Butler, B. Halliwell and I. O. Aruoma, Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol, Food Chem. Toxicol. 32 (1994) 31-36.CrossrefGoogle Scholar

  • T. Fujita, Y. Takeda, S. Han-dong, Y. Minami, T. Marunaka, S. Takeda, Y. Yamada and T. Togo, Cytotoxic and antitumor activities of Rabdosia diterpenoids, Planta Med. 54 (1988) 414-417; DOI: 10.1055/s-2006-962485.CrossrefPubMedGoogle Scholar

  • K. Gewald, E. Schink and H. Brottcher, Gewald aminothiophene synthesis, Chem. Ber. 99 (1966) 94-100.CrossrefGoogle Scholar

  • V. Alagarsamy, S. Meena, V. K. Ramseshu, R. V. Solomon, K. Thirumurugan, K Dhanabal and M. Murugan, Synthesis, analgesic, anti-inflammatory, ulcerogenic index and antibacterial activities of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno [2,3-d] pyrimidin-4(3H)-ones, Eur. J. Med. Chem. 41 (2006) 1293-1300. DOI: 10.1002/chin.200711131.CrossrefGoogle Scholar

About the article


Published Online: 2010-12-06

Published in Print: 2010-09-01


Citation Information: Acta Pharmaceutica, ISSN (Online) 1846-9558, ISSN (Print) 1330-0075, DOI: https://doi.org/10.2478/v10007-010-0027-6.

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