Skip to main content

Advertisement

SpringerLink
Log in

Facile synthesis and biological assays of novel 2,4-disubstituted hydrazinyl-thiazoles analogs

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A convenient, one-pot multi-component synthesis of new 2,4-disubstituted hydrazinyl-thiazoles was accomplished using different aldehydes/ketones, thiosemicarbazide, and 4-methoxy phenacyl bromide in the presence of a catalytic amount of AcOH in EtOH. Products were obtained in reasonable yields and high purity. The in vitro antioxidant activity of hydrazinyl-thiazoles was evaluated by DPPH radical scavenging activity in comparison to ascorbic acid. Synthesized thiazoles 14c and 14g possessed the lowest \(\hbox {IC}_{50}\) values. Also, hydrazinyl-thiazoles were screened for their in vitro antibacterial activity against six strains of bacteria including S. aureus, M. luteus, E. coli, Ps. aeruginosa, B. subtilis, and A. hydrophila where some products showed good antibacterial activity. Moreover, compound 14a showed anticancer activity against melanoma cancerous cell lines A375 with \(\hbox {LC}_{50}= 0.55\hbox { mg}/\hbox {mL}\), slightly selective versus normal cell lines (Hu-2) with \(\hbox {LC}_{50}= 1.19\hbox { mg}/\hbox {mL}\).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Scheme 1
Scheme 2
Fig. 3
Scheme 3
Fig. 4

Similar content being viewed by others

References

  1. Hargrave KD, Hess FK, Oliver JT (1983) \(N\)-(4-substituted-thiazolyl)oxamic acid derivatives, a new series of potent, orally active antiallergy agents. J Med Chem 26:1158–1163. doi:10.1021/jm00362a014

    Article  CAS  PubMed  Google Scholar 

  2. Patt WC, Hamilton HW, Taylor MD, Ryan MJ, Taylor DG Jr, Connolly CJC, Doherty AM, Klutchko SR, Sircar I, Steinbaugh BA, Batley BL, Painchaud CA, Rapundalo ST, Michniewicz BM, Olson SCJ (1992) Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors. J Med Chem 35:2562–2572. doi:10.1021/jm00092a006

    Article  CAS  PubMed  Google Scholar 

  3. Aggarwal R, Kumar S, Kaushik P, Dhirender K, Girish Kumar G (2013) Synthesis and pharmacological evaluation of some novel 2-(5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles. Eur J Med Chem 62:508–514. doi:10.1016/j.ejmech.2012.11.046

    Article  CAS  PubMed  Google Scholar 

  4. Cantrell AS, Engelhardt P, Högberg M, Jaskunas SR, Gunnar Johansson N, Jordan CL, Kangasmetsä J, Kinnick MD, Lind P, Morin JM, Muesing MA Jr, Noreén R, Öberg B, Pranc P, Sahlberg C, Ternansky RJ, Vasileff RT, Vrang L, West SJ, Zhang H (1996) Phenethythiazolethiourea (PETT) compounds; a new class of HIV-1 reverse transcriptase inhibitors. Synthesis and basic structure activity relationship studies of PETT analogs. J Med Chem 39:4261–4274. doi:10.1021/jm950639r

    Article  CAS  PubMed  Google Scholar 

  5. Jaen JC, Wise LD, Caprathe BW, Tecle H, Bergmeier S, Humblet CC, Heffner TG, Meltzner LT, Pugsley TA (1990) 4–1,2,5,6-Tetrahydro-l-alkyl-3-pyridinyl)-2-thizolamines: A novel class of compounds with central dopamine agonist properties. J Med Chem 33:311–317. doi:10.1021/jm00163a051

    Article  CAS  PubMed  Google Scholar 

  6. Tsuji K, Ishikawa H (1994) Synthesis and anti-pseudomonal activity of new 2-isocephems with a dihydroxypyridone moiety at C-7. Bioorg Med Chem Lett 4:1601–1606. doi:10.1016/S0960-894X(01)80574-6

    Article  CAS  Google Scholar 

  7. Jukič M, Đorđević A, Lazarević J, Gobec M, Šmelcerović A, Anderluh A (2013) Antimicrobial activity and cytotoxicity of some 2-amino-5-alkylidene-thiazol-4-ones. Mol Divers 17:773–780. doi:10.1007/s11030-013-9474-6

    Article  PubMed  Google Scholar 

  8. Li M, Sim Y, Wook Ham S (2010) Discovery of 2-aminothiazole derivatives as antitumor agents. Bull Korean Chem Soc 31:1463–1464. doi:10.5012/bkcs.2010.31.6.1463

    Article  CAS  Google Scholar 

  9. Regnier G, Canevar L, Le RJ, Douarec JC, Halstop S, Daussy J (1972) Triphenylpropylpiperazine derivatives as new potent analgetic substances. J Med Chem 15:295–301. doi:10.1021/jm00273a600

    Article  CAS  PubMed  Google Scholar 

  10. Siddiqui N, Waquar A (2010) Triazole incorporated thiazoles as a new class of anticonvulsants: Design, synthesis and in vivo screening. Eur J Med Chem 45:1536–1543. doi:10.1016/j.ejmech.2009.12.062

    Article  CAS  PubMed  Google Scholar 

  11. Ha YM, Uehara Y, Park D, Jeong HO, Park JY, Park YJ, Lee JY, Lee HJ, Song YM, Moon HR, Chung HY (2012) Synthesis and preliminary in vitro biological evaluation of 5-chloro-2-(substituted Phenyl)benzo[d]thiazole derivatives designed as novel antimelanogenesis agents. Appl Biochem Biotechnol 168:1416–1433. doi:10.1007/s12010-012-9867-5

    Article  CAS  PubMed  Google Scholar 

  12. Chandra Sekhar KVG, Rao VS, Deuther-Conrad W, Sridhar D, Nagesh HN, Kumar VS, Brust P, Kumar MMK (2013) Design, synthesis, and preliminary in vitro and in vivo pharmacological evaluation of 4-{4-[2-(4-(2-substitutedquinoxalin-3-yl)piperazin-1-yl)ethyl]phenyl}thiazoles as atypical antipsychotic agents. Med Chem Res 22:1660–1673. doi:10.1007/s00044-012-0164-1

    Article  CAS  Google Scholar 

  13. Anbazhagan R, Sankaran KR (2013) Syntheses, spectral characterization, single crystal X-ray diffraction and DFT computational studies of novel thiazole derivatives. J Mol Struct 1050:73–80. doi:10.1016/j.molstruc.2013.07.019

    Article  CAS  Google Scholar 

  14. McIntyre NA, McInnes C, Griffiths G, Barnett AL, Kontopidis G, Slawin AM, Jackson W, Thomas M, Zheleva DI, Wang S, Blake DG, Westwood NJ, Fischer PM (2010) Design, synthesis, and evaluation of 2-methyl- and 2-amino-\(N\)-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors. J Med Chem 53:2136–2145. doi:10.1021/jm901660c

    Article  CAS  PubMed  Google Scholar 

  15. Mohammed Khan K, Karim A, Saied S, Ambreen N, Rustamova X, Naureen S, Mansoor S, Ali M, Perveen S, Choudhary MI, Antonio Morales G (2014) Evaluation of the thiazole Schiff bases as \(\beta \) -glucuronidase inhibitors and their in silico studies. Mol Divers 18:295–306. doi:10.1007/s11030-013-9500-8

    Article  Google Scholar 

  16. Imramovsky A, Pejchal V, Štepánková Š, Vorcáková K, Jampílek J, Vancod J, Šimunek P, Královec K, Brucková L, Mandíková J, Trejtnar F (2013) Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors. Bioorg Med Chem 21:1735–1748. doi:10.1016/j.bmc.2013.01.052

    Article  CAS  PubMed  Google Scholar 

  17. Carradori S, Secci D, Bolasco A, Rivanera D, Mari E, Zicari A, Lotti LV, Bizzarri B (2013) Synthesis and cytotoxicity of novel (thiazol-2-yl)hydrazine derivatives as promising anti-candida agents. Eur J Med Chem 65:102–111. doi:10.1016/j.ejmech.2013.04.042

    Article  CAS  PubMed  Google Scholar 

  18. Abbasi Shiran J, Yahyazadeh A, Mamaghani M, Rassa M (2013) Regioselective synthesis of novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole and \(2,2^\prime \)-(1,3-phenylene)bis(3-substituted-2-imino-4-phenyl-3H-thiazole) derivatives as antibacterial agents. J Mol Struct 1039:113–118. doi:10.1016/j.molstruc.2013.02.003

    Article  CAS  Google Scholar 

  19. Kudrjasova J, Herckens R, Penxten H, Adriaensens P, Lutsen L, Vanderzandea D, Maes W (2014) Direct arylation as a versatile tool towards thiazolo[5,4-d]thiazole-based semiconducting materials. Org Biomol Chem 12:4663–4672. doi:10.1039/C4OB00360H

    Article  CAS  PubMed  Google Scholar 

  20. Giridhar T, Cho W, Park J, Park J-S, Gal Y-S, Kang S, Leec JY, Jin S-H (2013) Facile synthesis and characterization of iridium(III) complexes containing an N-ethylcarbazole-thiazole main ligand using a tandem reaction for solution processed phosphorescent organic light-emitting diodes. J Mater Chem C 1:2368–2378. doi:10.1039/C3TC00323J

    Article  CAS  Google Scholar 

  21. Hela A, Harun M, Choi C-H, Kima H-S (2012) New regioisomeric naphthol-substituted thiazole based ratiometric fluorescence sensor for \(\text{ Zn }^{2+}\) with a remarkable red shift in emission spectra. Tetrahedron 68:647–653. doi:10.1016/j.tet.2011.10.106

    Article  Google Scholar 

  22. Sharifzadeh B, Mahmoodi NO, Mamaghani M, Tabatabaeian K, Salimi Chirani A, Nikokar I (2013) Facile regioselective synthesis of novel bioactive thiazolyl-pyrazoline derivatives via a three-component reaction and their antimicrobial activity. Bioorg Med Chem Lett 23:548–551. doi:10.1016/j.bmcl.2012.11.024

  23. Mahmoodi NO, Parvizi J, Sharifzadeh B, Rassa M (2013) Facile regioselective synthesis of novel bis-thiazole derivatives and their antimicrobial activity. Arch Pharm Chem Life Sci 346:860–864. doi:10.1002/ardp.201300187

    Article  CAS  Google Scholar 

  24. Mahmoodi NO, Safari N, Sharifzadeh B (2014) One-Pot synthesis of novel 2-(thiazol-2-yl)-4,5-dihydropyridazin-\(3(2H)\)-one derivatives catalyzed by activated KSF. Synth Commun 44:245–250. doi:10.1080/00397911.2013.801077

  25. Mahmoodi NO, Ramzanpour S, Ghanbari Pirbasti F (2015) One-pot multi-component synthesis of 1,4-dihydropyridines using \(\text{ Zn }^{2+}\)@KSF and evaluation their antibacterial and antioxidant activities. Arch der Pharm 348:275–282. doi:10.1002/ardp.201400414

    Article  CAS  Google Scholar 

  26. Mahmoodi NO, Mamaghani M, Behzadi T (2012) Synthesis and structure-behavior relationships of tetra-substituted imidazole derivatives of 1, 3-diazabicyclo [3, 1, 0] hex-3-ene. Mol Divers 16:737–747. doi:10.1007/s11030-012-9409-7

    Article  CAS  PubMed  Google Scholar 

  27. Caputto ME, Ciccarelli A, Frank F, Moglioni AG, Moltrasio GY, Vega D, Lombardo E, Finkielsztein LM (2012) Synthesis and biological evaluation of some novel 1-indanone thiazolylhydrazone derivatives as anti-trypanosoma cruzi agents. Eur J Med Chem 55:155–163. doi:10.1016/j.ejmech.2012.07.013

    Article  CAS  PubMed  Google Scholar 

  28. Secci D, Bolasco A, Carradori S, D’Ascenzio M, Nescatelli R, Yáñez M (2012) Recent advances in the development of selective human MAO-B inhibitors: (Hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines. Eur J Med Chem 58:405–417. doi:10.1016/j.ejmech.2012.10.032

    Article  CAS  PubMed  Google Scholar 

  29. Gaikwad ND, Patil SV, Bobade VD (2012) Hybrids of ravuconazole: synthesis and biological evaluation. Eur J Med Chem 54:295–302. doi:10.1016/j.ejmech.2012.05.010

    Article  CAS  PubMed  Google Scholar 

  30. Arshad A, Osman H, Bagley MC, Kit Lam C, Mohamad S, Safirah A, Zahariluddin M (2011) Synthesis and antimicrobial properties of some new thiazolyl coumarin derivatives. Eur J Med Chem 46:3788–3794. doi:10.1016/j.ejmech.2011.05.044

    Article  CAS  PubMed  Google Scholar 

  31. Hassan AA, Ibrahim YR, El-Sheref EM, Abdel-Aziz M, Bräse S, Nieger M (2013) Synthesis and antibacterial activity of 4-aryl-2-(1-substituted ethylidene)thiazoles. Arch Pharm Chem Life Sci 346:562–570. doi:10.1002/ardp.201300099

    Article  CAS  Google Scholar 

  32. Osman H, Arshad A, Kit Lam C, Bagley MC (2012) Microwave-assisted synthesis and antioxidant properties of hydrazinyl thiazolyl coumarin derivatives. Chem Cent J 6:32. doi:10.1186/1752-153X-6-32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bharti SK, Nath G, Tilak R, Singh SK (2010) Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring. J Med Chem 45:651–660. doi:10.1016/j.ejmech.2009.11.008

    Article  CAS  Google Scholar 

  34. Alam MS, Liu L, Lee YE, Lee DU (2011) Cytotoxicity of new 5-phenyl-4,5-dihydro-1,3,4-thiadiazole analogues. Chem Pharm Bull 59:568–573. doi:10.1002/chin.201215131

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are greatly thankful to Dr. Zohreh Ramezanpour and Miss Somaie Rasouli Dogaheh for their helpful assistance in running biological assays. The authors appreciate the valuable and helpful comments of Professor Dr. Guillermo A. Morales, Editor-In-Chief of Molecular Diversity.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Guilan, P.O. Box 41335-1914, Rasht, Iran

    Fateme Ghanbari Pirbasti & Nosrat O. Mahmoodi

Authors
  1. Fateme Ghanbari Pirbasti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nosrat O. Mahmoodi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nosrat O. Mahmoodi.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (docx 3907 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghanbari Pirbasti, F., Mahmoodi, N.O. Facile synthesis and biological assays of novel 2,4-disubstituted hydrazinyl-thiazoles analogs. Mol Divers 20, 497–506 (2016). https://doi.org/10.1007/s11030-015-9654-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-015-9654-7

Keywords

Search

Navigation