Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

4 Issues per year


IMPACT FACTOR 2016: 1.288
5-year IMPACT FACTOR: 1.600

CiteScore 2016: 1.55

SCImago Journal Rank (SJR) 2016: 0.353
Source Normalized Impact per Paper (SNIP) 2016: 0.854

Open Access
Online
ISSN
1846-9558
See all formats and pricing
More options …
Volume 63, Issue 1 (Mar 2013)

Issues

Synthesis and anti-tumor evaluation of novel hydrazide and hydrazide-hydrazone derivatives

Wagnat Wahba Wardakhan / El-Sayed Nahed Nasser Eid
  • National Organization for Drug Control and Research P.O. 29 Cairo, A. R. Egypt
  • College of Science, Department of Chemistry, King Saud University Women Students – Medical Studies and Science Sections P.O. Box 22452, Riyadh 11495 Kingdom of Saudi Arabia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rafat Milad Mohareb
Published Online: 2013-03-12 | DOI: https://doi.org/10.2478/acph-2013-0004

The reaction of cyclopentanone with cyanoacetylhydrazine gave 2-cyano-2-cyclopentylideneacetohydrazide (1). Treatment of compound 1 with elemental sulphur in the presence of triethylamine afforded 2-amino-5,6-dihydro- -4H-cyclopenta[b]thiophene-3-carbohydrazide (2), which in-turn formed the corresponding intermediate diazonium salt. The latter was coupled with either ethyl cyanoacetate or ethyl acetoacetate to form 2-cyano-2-(3-(hydrazinecarbonyl)- 5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)hydrazono) acetate (3) and ethyl 2-(2-(3-(hydrazinecarbonyl)-5,6-dihydro- 4H-cyclopenta[b]thiophen-2-yl)hydrazono)-3-oxobutanoate (4), respectively. On the other hand, the reaction of compound 1 with either benzaldehyde or acetophenone afforded N’-benzylidene-2-cyano-2-cyclopentylideneacetohydrazide (7) and 2-cyano-2-(2-cyclopentylidene)phenylacetohydrazide (10), respectively. Moreover, compound 1 was used to synthesize 2-cyano-2-cyclopentylidene- N'-(arylthiazol-2(3H)-ylidene)acetohydrazides (6a,b), 2-(2-benzylidenecyclopentylidene)-2-cyanoacetohydrazide (8), 2-amino-N'-benzylidene-5,6-dihydro-4H- -cyclopenta[b]thiophene-3-carbohydrazide (9), 2-cyano- -2-(2-(2-phenylhydrazono)cyclopentylidene)acetohydrazide (11), N'-(1-chloropropan-2-ylidene)-2-cyano-2-cyclopentylideneacetohydrazide (12), and 2-cyclopentylidene-3- -(3,5-disubstituted-1H-pyrazol-1-yl)-3-oxopropanenitriles (13a,b) through its reaction with the respective reagents. Antitumor evaluation of the newly synthesized compounds against the three human tumor cells lines, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of the described compounds exhibited higher inhibitory effects towards the three tumor cell lines than the reference compound doxorubicin.

Keywords: hydrazide; hydrazide-hydrazone; thiophene; pyrazole; antitumor

  • 1. S. K. Bharti, G. Nath, R. Tilak and S. K. Singh, Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring, Eur. J. Med. Chem. 45 (2010) 651-660; DOI: 10.1016/j.ejmech.2009.11.008.CrossrefGoogle Scholar

  • 2. C. Loncle, J. M. Brunel, N. Vidal, M. Dherbomez and Y. Letourneux, Synthesis and antifungal activity of cholesterol-hydrazone derivatives, Eur. J. Med. Chem. 39 (2004) 1067-1071; DOI: 10.1016/ j.ejmech.2004.07.005.CrossrefGoogle Scholar

  • 3. S. P. Garoufalias, N. Pouli, P. Marakos and A. C. Ladas, Synthesis, antimicrobial and antifungal activity of some new 3-substituted derivatives of 4-(2,4-dichlorophenyl)-5-adamantyl-1H-1,2,4- -triazole, Farmaco 57 (2002) 973-977; DOI: 10.1016/S0014-827X(02)01273-9.CrossrefGoogle Scholar

  • 4. P. Vicini, F. Zani, P. Cozzini and I. Doytchinova, Hydrazones of 1,2-benzisothiazole hydrazides: synthesis, antimicrobial activity and QSAR investigations, Eur. J. Med. Chem. 37 (2002) 553-567; DOI: 10.1016/S0223-5234(02)01378-8.CrossrefGoogle Scholar

  • 5. F. D. Popp, Potential anticonvulsant. XII. Anticonvulsant activity of some aldehyde derivatives, Eur. J. Med. Chem. 24 (1989) 313-316; DOI: 10.1016/0223-5234(89)90016-0.CrossrefGoogle Scholar

  • 6. S. K. Sridhar, S. N. Pandeya, J. P. Stables and R. Atmakuru, Anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin derivatives, Eur. J. Pharm. Sci. 16 (2002) 129-132; DOI: 10.1016/S0928-0987(02)00077-5.CrossrefGoogle Scholar

  • 7. S. G. Küçükgüzel, S. Rollas, I. Küçükgüzel and M. Kiraz, Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones, Eur. J. Med. Chem. 34 (1999) 1093-1100; DOI: 10.1016/S0223-5234(99)00129-4.CrossrefGoogle Scholar

  • 8. B. K. Kaymakçýoǧlu and S. Rollas, Synthesis, characterization and evaluation of antituberculosis activity of some hydrazones, Farmaco 57 (2002) 595-599; DOI: 10.1016/S0014-827X(02)01255-7.CrossrefGoogle Scholar

  • 9. S. G. Küçükgüzel, A. Mazi, F. Sahin, S. Öztürk and J. P. Stables, Synthesis and biological activities of diflunisal hydrazide-hydrazones, Eur. J. Med. Chem. 38 (2003) 1005-1013; DOI: 10.1016/ j.ejmech.2003.08.004.CrossrefGoogle Scholar

  • 10. A. R. Todeschini, A. L. P. de Miranda, K. C. M. da Silva, S. C. Parrini and E. Barreiro, Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2-pyridylarylhydrazone derivatives, Eur. J. Med. Chem. 33 (1998) 189-199; DOI: 10.1016/S0223-5234(98)80008-1.CrossrefGoogle Scholar

  • 11. M. A. Gaston, L. R. S. Dias, A. C. C. Freitas, A. L. P. Miranda and E. J. Barreiro, Synthesis and analgesic properties of new 4-arylhydrazone 1H pyrazole[3,4-b]pyridine derivatives, Pharm. Acta Helv. 71 (1996) 213-219; DOI: 10.1016/0031-6865(96)00012-X.CrossrefGoogle Scholar

  • 12. P. Melnyk, V. Leroux, C. Sergheraert and P. Grellier, Design, synthesis and in vitro antimalarial activity of an acylhydrazone library, Bioorg. Med. Chem. Lett. 16 (2006) 31-35; DOI: 10.1016/j.bmcl. 2005.09.058.CrossrefGoogle Scholar

  • 13. N. Terzioglu and A. Gursoy, Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazide, Eur. J. Med. Chem. 38 (2003) 781-786; DOI: 10.1002/chin.200401111.CrossrefGoogle Scholar

  • 14. S. M. Sondhi, M. Dinodia and A Kumar, Synthesis, anti-inflammatory and analgesic activity evaluation of some amidine and hydrazone derivatives, Bioorg. Med. Chem. 14 (2006) 4657-4663; DOI: 10.1016/j.bmc.2006.02.014.CrossrefPubMedGoogle Scholar

  • 15. C. Boga, L. Fiume, M. Baglioni, C. Bertucci, C. Farina, F. Kratz, M. Manerba, M. Naldi and G. Stefano, Characterisation of the conjugate of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin with lactosaminated human albumin by 13C NMR spectroscopy, Eur. J. Pharm. Sci.38 (2009) 262-269; DOI: 10.1016/j.ejps.2009.08.001.CrossrefWeb of ScienceGoogle Scholar

  • 16. M. C. Garnett, Targeted drug conjugates: principles and progress, Adv. Drug Deliv. Rev. 53 (2001) 171-216; DOI: 10.1016/S0169-409X(01)00227-7.CrossrefGoogle Scholar

  • 17. P. C. Rodrigues, K. Scheuermann, C. Stockmar, G. Maier, H. Fiebig, C. Unger, R. Mülhaupt and F. Kratz, Synthesis and in-vitro efficacy of acid-sensitive poly(ethylene glycol) paclitaxel conjugates, Bioorg. Med. Chem. Lett. 13 (2003) 355-360; DOI: 10.1016/S0960-894X(02)01002-8.CrossrefGoogle Scholar

  • 18. O. I. El-Sabbagh and H. M. Rady, Synthesis of new acridines and hydrazones derived from cyclic â-diketone for cytotoxic and antiviral evaluation, Eur. J. Med. Chem. 44 (2009) 3680-3686; DOI: 10.1002/chin.200948062.CrossrefGoogle Scholar

  • 19. H. Krakovicova, T. Etrych and K. Ulbrich, HPMA-based polymer conjugates with drug combination, Eur. J. Pharm. Sci. 37 (2009) 405-412; DOI: 10.1016/j.ejps.2009.03.011.CrossrefGoogle Scholar

  • 20. H. Z. Zhang, J. Drewe, B. Tseng, S. Kasibhatla and S. X. Cai, Discovery and SAR of indole-2- -carboxylic acid benzylidene-hydrazides as a new series of potent apoptosis inducers using a cell-based HTS assay, Bioorg. Med. Chem. 12 (2004) 3649-3655; DOI: 10.1016/j.bmc.2004.04.017.CrossrefGoogle Scholar

  • 21. P. Vicini, M. I. Incerti, P. L. Colla and R. Loddo, Anti-HIV evaluation of benzo[d]isothiazole hydrazones, Eur. J. Med. Chem. 44 (2009) 1801-1807; DOI: 10.1016/j.ejmech.2008.05.030.CrossrefGoogle Scholar

  • 22. V. M. Rahman, S. Mukhtar, W. H. Ansari and G. Lemiere, Synthesis, stereochemistry and biological activity of some novel long alkyl chain substituted thiazolidin-4-ones and thiazan-4-one from 10- undecenoic acsid hydrazide, Eur. J. Med. Chem. 40 (2005) 173-184; DOI: 10.1016/j.ejmech.2004. 10.003.CrossrefGoogle Scholar

  • 23. J. R. Dimmock, S. C. Vashishtha and J. P. Stables, Anticonvulsant properties of various acetylhydrazones, oxamoylhydrazones and semicarbazones derived from aromatic and unsaturated carbonyl compounds, Eur. J. Med. Chem. 35 (2000) 241-248; DOI: 10.1016/S0223-5234(00)00123-9.CrossrefGoogle Scholar

  • 24. D. Kaushik, S. A. Khan, G. Chawla and S. Kumar, N'-[5-chloro-3-methyl-1-phenyl-1H-pyrazol- -4-yl)methylene]2/4-substituted hydrazide: Synthesis and anticonvulsant activity, Eur. J. Med. Chem. 45 (2010) 3943-3949; DOI: 10.1016/j.ejmech.2010.05.049.CrossrefWeb of ScienceGoogle Scholar

  • 25. S. G. Küçükgüzel, A. Mazi, F. Sahin, S. Öztürk and J. Stables, Synthesis and biological activities of diflunisal hydrazide-hydrazones, Eur. J. Med. Chem. 38 (2003) 1005-1013. DOI: 10.1016/ j.ejmech.2003.08.004.CrossrefGoogle Scholar

  • 26. Y. L. Xia, F. Chuan-Dong, B. X. Zhao, J. Zhao, D. S. Shin and J. Y. Miaom, Synthesis and structure- activity relationships of novel 1-arylmethyl-3-aryl-1H pyrazole-5-carbohydrazide hydrazone derivatives as potential agents against A549 lung cancer cells, Eur. J. Med. Chem. 43 (2008) 2347-2353; DOI: 10.1016/j.ejmech.2008.01.021.Web of ScienceCrossrefGoogle Scholar

  • 27. C. Menendez, A. Chollet, F. Rodriguez, C. Inard, M. R. Pasca, C. Lherbet and M. Baltas, Chemical synthesis and biological evaluation of triazole derivatives as inhibitors of InhA and antituberculosis agents, Eur. J. Med. Chem. 52 (2012) 275-283; DOI: 10.1016/j.ejmech.2012.03.029.CrossrefGoogle Scholar

  • 28. N. Özbek, S. Alyar and N. Karacan, Experimental and theoretical studies on methanesulfonic acid 1-methylhydrazide: Antimicrobial activities of its sulfonyl hydrazone derivatives, J. Mol. Struct. 938 (2009) 48-53; DOI: 10.1016/j.molstruc.2009.09.002.Web of ScienceCrossrefGoogle Scholar

  • 29. R. M. Mohareb and J. Schatz, Anti-tumor and anti-leishmanial evaluations of 1,3,4-oxadiazine, pyran derivatives derived from cross-coupling reactions of b-bromo-6H-1,3,4-oxadiazine derivatives, Bioorg. Med. Chem. 19 (2011) 2707-2713; DOI: 10.1016/j.bmc.2011.02.051.CrossrefWeb of ScienceGoogle Scholar

About the article

Published Online: 2013-03-12

Published in Print: 2013-03-01


Citation Information: Acta Pharmaceutica, ISSN (Online) 1846-9558, ISSN (Print) 1330-0075, DOI: https://doi.org/10.2478/acph-2013-0004.

Export Citation

This content is open access.

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
R. Mohammed Shafeeulla, G. Krishnamurthy, H.S. Bhojynaik, H.P. Shivarudrappa, and Yallappa Shiralgi
Beni-Suef University Journal of Basic and Applied Sciences, 2017
[3]
Elham Mousavi, Shahrzad Tavakolfar, Ali Almasirad, Zahra Kooshafar, Soudeh Dehghani, Ahoo Afsharinasab, Amir Amanzadeh, Samira Shafiee, and Mona Salimi
Cancer Chemotherapy and Pharmacology, 2017, Volume 79, Number 6, Page 1195
[4]
Vanita D. Saharan and Supriya S. Mahajan
Bioorganic & Medicinal Chemistry Letters, 2017, Volume 27, Number 4, Page 808
[6]
Fatima Al-Omran and Adel Abou El-Khair
International Journal of Organic Chemistry, 2016, Volume 06, Number 01, Page 31
[7]
Kristina Mickevičienė, Rūta Baranauskaitė, Kristina Kantminienė, Maryna Stasevych, Olena Komarovska-Porokhnyavets, and Volodymyr Novikov
Molecules, 2015, Volume 20, Number 2, Page 3170
[8]
Zhou-Qin Xu, Xian-Jie Mao, Lei Jia, Jun Xu, Tao-Feng Zhu, Hong-Xin Cai, Hong-Yan Bie, Ru-Hua Chen, and Tie-liang Ma
Journal of Molecular Structure, 2015, Volume 1102, Page 86
[10]
Felipe A.R. Rodrigues, Igor da S. Bomfim, Bruno C. Cavalcanti, Claudia do Ó. Pessoa, James L. Wardell, Solange M.S.V. Wardell, Alessandra C. Pinheiro, Carlos Roland Kaiser, Thais C.M. Nogueira, John N. Low, Ligia R. Gomes, and Marcus V.N. de Souza
Bioorganic & Medicinal Chemistry Letters, 2014, Volume 24, Number 3, Page 934

Comments (0)

Please log in or register to comment.
Log in