Skip to main content
SpringerLink
Log in

Novel quinolyl-thienyl chalcones and their 2-pyrazoline derivatives with diverse substitution pattern as antileishmanial agents against Leishmania major

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A series of twenty-two new pyrazoline derivatives was prepared from quinoline-based chalcones which in turn were synthesized by condensing formylquinolines with diverse acetylthiophenes. The titled compounds were characterized by spectroscopic techniques (NMR, IR and MS) and elemental analysis. All the compounds were screened for antileishmanial activities. Compounds 1e, 1f, 2a, 2c, 2d, 2g, 2k, and 4a were found potentially active antileishmanial agents. Bioassay results show that the type and positions of the substituents seem to be critical for their antileishmanial activities.

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
Scheme 1
Fig. 2

Similar content being viewed by others

References

  • Alhaider AA, Abdelkader MA, Lien EJ (1985) Design, synthesis, and pharmacological activities of 2-substituted 4-phenyl quinolines as potential antidepressant drugs. J Med Chem 28:1394–1398

    Article  PubMed  CAS  Google Scholar 

  • Ali SA, Iqbal J, Yasinzai MM (1997) In vitro maintenance of Leishmania promastigote in an egg based biphasic culture medium. Methods Cell Sci 19:107–110

    Article  Google Scholar 

  • Althuis TH, Khadin SB, Czuba LJ, Moore PF, Hess HJ (1980) Structure-activity relationships in a series of novel 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylic acid antiallergy agents. J Med Chem 23:262–269

    Article  PubMed  CAS  Google Scholar 

  • Awad IMA, Abdel-Rehman AE, Bakhite EA (1991) Synthesis and application of some new S-(substituted) thio- and thienoquinoline derivatives as antimicrobial agents. Collect Czech Chem Commun 56:1749–1760

    Article  CAS  Google Scholar 

  • Azarifar D, Shaebanzadeh M (2002) Synthesis and characterization of new 3,5-dinaphthyl substituted 2-pyrazolines and study of their antimicrobial activity. Molecules 7:885–895

    Article  CAS  Google Scholar 

  • Ballesteros JF, Sanz MJ, Ubeda A, Miranda MA, Iborra S, Paya M, Alcaraz M (1995) Synthesis and pharmacological evaluation of 2′-hydroxychalcones and flavones as inhibitors of inflammatory mediators generation. J Med Chem 38:2794–2797

    Article  PubMed  CAS  Google Scholar 

  • Barsoum FF, Hosni HM, Girgis AS (2006) Novel bis(1-acyl-2-pyrazolines) of potential anti-inflammatory and molluscicidal properties. Bioorg Med Chem 14:3929–3937

    Article  PubMed  CAS  Google Scholar 

  • Bilgin AA, Palaska E, Sunal R (1993) Studies on the synthesis and antidepressant activity of some 1-thiocarbamoyl-3,5-diphenyl-2-pyrazolines. Arzneimforsch Drug Res 43:1041–1044

    CAS  Google Scholar 

  • Boeck P, Falcão CAB, Leal PC, Yunes RA, Filho VC, Santos ECT, Bergmann BR (2006) Synthesis of chalcone analogues with increased antileishmanial activity. Bioorg Med Chem 14:1538–1545

    Article  PubMed  CAS  Google Scholar 

  • Budakoti A, Abid M, Azam A (2006) Synthesis and antiamoebic activity of new 1-N-substituted thiocarbamoyl-3,5-diphenyl-pyrazoline derivatives and their Pd(ll) complexes. Eur J Med Chem 41:63–70

    Article  PubMed  CAS  Google Scholar 

  • Campbell SF, Hardstone JD, Palmer MJ (1988) 2,4-Diamino-6,7-dimethoxyquinoline derivatives as alpha1-adrenoceptor antagonists and antihypertensive agents. J Med Chem 31:1031–1035

    Article  PubMed  CAS  Google Scholar 

  • Dillard RD, Pavey DE, Benslay DN (1973) Synthesis and antiinflammatory activity of some 2,2-dimethyl-1,2-dihydroquinolines. J Med Chem 16:251–253

    Article  PubMed  CAS  Google Scholar 

  • Du W (2003) Towards new anticancer drugs: a decade of advances in synthesis of camptothecins and related alkaloids. Tetrahedron 59:8649–8687

    Article  CAS  Google Scholar 

  • Ginsburg H, Ward SA, Bray PG (1999) An integrated model of chloroquine action. Parasitol Today 15:357–360

    Article  PubMed  CAS  Google Scholar 

  • Lévai A (2005) Synthesis of chlorinated 3,5-diaryl-2-pyrazolines by the reaction of chlorochalcones with hydrazines. ARKIVOC 9:344–352

    Google Scholar 

  • Lévai A, Silva AMS, Pinto DCGA, Cavaleiro JAS, Alkorta I, Elguero J, Jekő J (2004) Synthesis of pyrazolyl-2-pyrazolines by treatment of 3-(3-aryl-3-oxopropenyl)-chromen-4-ones with hydrazine and their oxidation to bis(pyrazoles). Eur J Org Chem 2004:4672–4679

    Article  Google Scholar 

  • Li R, Kenyon GL, Cohen FE, Chen X, Gong B, Dominguez JN, Davidson E, Kurzban G, Miller RE, Nuzum EO, Rosenthal PJ, McKerrow JH (1995) In vitro antimalarial activity of chalcones and their derivatives. J Med Chem 38:5031–5037

    Article  PubMed  CAS  Google Scholar 

  • Loaiza PR, Quintero A, Rodríguez-Sotres R, Solano JD, Rocha AL (2004) Synthesis and evaluation of 9-anilinothiazolo[5,4-b]quinoline derivatives as potential antitumorals. Eur J Med Chem 39:5–10

    Article  Google Scholar 

  • Manske RHF, Kulka M (1953) The skraup synthesis of quinolines. Org React 7:59–98

    Google Scholar 

  • Meth-Cohn O (1993) The synthesis of pyridines, quinolines and other related systems by the Vilsmeier and reverse Vilsmeier method. Heterocycles 35:539–557

    Article  CAS  Google Scholar 

  • Meth-Cohn O, Narine B (1978) A versatile new synthesis of quinolines, thiopyrimidines and related fused pyridines. Tetrahedron Lett 23:2045–2048

    Article  Google Scholar 

  • Meth-Cohn O, Narine B, Tarnowski B (1981) A versatile new synthesis of quinolines and related fused pyridines, Part 5. The synthesis of 2-chloroquinoline-3-carbaldehydes. J Chem Soc Perkin Trans I 1520–1530

  • Michael JP (2003) Quinoline, quinazoline and acridone alkaloids. Nat Prod Rep 20:476–493

    Article  PubMed  CAS  Google Scholar 

  • Michael JP (2004) Quinoline, quinazoline and acridone alkaloids. Nat Prod Rep 21:650–668

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S, Kumar V, Prasad AK, Raj HG, Brakhe ME, Olsen CE, Jain SC, Parmar VP (2001) Synthetic and biological activity evaluation studies on novel 1,3-diarylpropenones. Bioorg Med Chem 9:337–339

    Article  PubMed  CAS  Google Scholar 

  • Nauduri D, Reddy GB (1998) Antibacterial and antimycotics : Part 1: synthesis and activity of 2-pyrazoline derivatives. Chem Pharm Bull Tokyo 46:1254–1260

    Article  PubMed  CAS  Google Scholar 

  • Nowakowska Z (2007) A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 42:125–137

    Article  PubMed  CAS  Google Scholar 

  • Ozdemir Z, Kandilici HB, Gumusel B, Calis U, Bilgin AA (2007) Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 42:373–379

    Article  PubMed  Google Scholar 

  • Ramalingham K, Thyvekikakath GX, Berlin KD, Chesnut RW, Brown RA, Durham NN, Ealick SE, Van der Helm D (1977) Synthesis and biological activity of some derivatives of thiochroman-4-one and tetrahydrothiapyran-4-one. J Med Chem 20:847–850

    Article  Google Scholar 

  • Rezende RM, Paiva-Lima P, Reis WGPD, Camêlo VM, Bakhle YS, de Francischi JN (2010) Celecoxib induces tolerance in a model of peripheral inflammatory pain in rats. Neuropharmacology 59:551–557

    Article  PubMed  CAS  Google Scholar 

  • Rizvi UF, Siddiqui HL, Ahmad S, Ahmad M, Parvez M (2008) Novel chalcones derived from 2-chloro-6-methylquinoline. Acta Crystallogr C 64:547–549

    Article  Google Scholar 

  • Shibata S (1994) Anti-tumorigenic chalcones. Stem Cells 12:44–52

    Article  PubMed  CAS  Google Scholar 

  • Singh SP, Parmar SS, Stenberg VI (1978) Carbon-13 nuclear magnetic resonance spectra of potent antimalarials: primaquine and chloroquine. J Heterocycl Chem 15:9–11

    Article  CAS  Google Scholar 

  • Sivakumar PM, Geetha BabuSK, Mukesh D (2007) QSAR studies on chalcones and flavonoids as anti-tuberculosis agents using genetic function approximation (GFA) method. Chem Pharm Bull 55:44–49

    Article  PubMed  CAS  Google Scholar 

  • Taylor EC, Patel HH (1992) Synthesis of pyrazolo[3,4,-d]pyrimidine analogues of the potent antitumor agent N-{4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-l-glutamic acid (LY231514). Tetrahedron 48:8089–8100

    Article  CAS  Google Scholar 

  • Trivedi JC, Bariwal JB, Upadhyay KD, Naliapara YT, Joshi SK, Pannecouque CC, Clercq ED, Shah AK (2007) Improved and rapid synthesis of new coumarinyl chalcone derivatives and their antiviral activity. Tetrahedron Lett 48:8472–8474

    Article  CAS  Google Scholar 

  • Viana GS, Bandeira MA, Matos F (2003) Analgesic and antiinflamatory effects of chalcones isolated from Myracrodrum urundeiva. J Phytomedicine 10:189–195

    Article  CAS  Google Scholar 

  • Wattenberg LW, Coccia JB, Galbraith AR (1994) Inhibition of carcinogen-induced pulmonary and mammarycarcinogenesis by chalcone administered subsequent to carcinogen exposure. Cancer Lett 83:165–169

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Wilairat P, Go M (2002) Antimalarial activity of ferrocenyl chalcones. Bioorg Med Chem Lett 12:2299–2302

    Article  PubMed  CAS  Google Scholar 

  • Wu JH, Wang XH, Yi YH, Lee KH (2003) Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos. Bioorg Med Chem Lett 13:1813–1815

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The author is grateful to Higher Education Commission, Pakistan and Institute of Chemistry, University of the Punjab, Lahore, for financial support. We are also thankful to International Centre for Chemical and Biological Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi, for spectral measurements and Dr. M. Masoom Yasinzai, Institute of Biochemistry, University of Balochistan, Quetta, Pakistan for evaluation of antileishmanial activities.

Author information

Authors and Affiliations

  1. Institute of Chemistry, University of the Punjab, Lahore, 54590, Pakistan

    Syed Umar Farooq Rizvi, Hamid Latif Siddiqui, Matloob Ahmad & Mujahid Hussain Bukhari

  2. Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan

    Muhammad Nisar Ahmad

Authors
  1. Syed Umar Farooq Rizvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hamid Latif Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhammad Nisar Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matloob Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mujahid Hussain Bukhari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hamid Latif Siddiqui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rizvi, S.U.F., Siddiqui, H.L., Ahmad, M.N. et al. Novel quinolyl-thienyl chalcones and their 2-pyrazoline derivatives with diverse substitution pattern as antileishmanial agents against Leishmania major . Med Chem Res 21, 1322–1333 (2012). https://doi.org/10.1007/s00044-011-9647-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-011-9647-8

Keywords

Search

Navigation