Skip to main content
Log in

Perspective: the potential of pyrazole-based compounds in medicine

  • Published:
BioMetals Aims and scope Submit manuscript

Abstract

Pyrazoles are widely used as core motifs for a large number of compounds for various applications such as catalysis, agro-chemicals, building blocks of other compounds and in medicine. The attractiveness of pyrazole and its derivatives is their versatility that allows for synthesis of a series of analogues with different moieties in them, thus affecting the electronics and by extension the properties of the resultant compounds. In medicine pyrazole is found as a pharmacophore in some of the active biological molecules. While pyrazole derivatives have been extensively studied for many applications including anticancer, antimicrobial, anti-inflammatory, antiglycemic, anti-allergy and antiviral, much less has been reported on their metal counterparts in spite of the fact that metals have been shown to impart activity to ligands. Thus this perspective is intended to demonstrate the potential of pyrazole and pyrazolyl metal complexes in the areas of drug discovery and development. Several examples, that include palladium, platinum, copper, gold, zinc, cobalt, nickel, iron, copper, silver and gallium complexes, are used to bolster the above point. For the purposes of this review three areas are discussed, that is pyrazole metal complexes as: (i) anticancer, (ii) antibacterial/parasitic and (iii) antiviral agents.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abunada NM, Hassaneen HM, Kandile NG, Miqdad OA (2008) Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3, 4-d]-pyrimidine and Pyrazolo[4, 3-e][1, 2, 4]-triazolo[1, 5-c]pyrimidine derivatives. Molecules 13:1501–1517

    Article  PubMed  CAS  Google Scholar 

  • Adnan AB, Abdel-Aziem T (2004) Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory-antimicrobial agents. Bioorg Med Chem 12:1935–1945

    Article  CAS  Google Scholar 

  • Aiello E, Aiello S, Mingoia F, Bacchi A, Pelizzi G, Musiu C, Setzu MG, Pani A, La Colla P, Marongiu ME (2000) Synthesis and antimicrobial activity of new 3-(1-R-3(5)-methyl-4-nitroso-1H-5(3)-pyrazolyl)-5-methylisoxazoles. Bioorg Med Chem 8:2719–2728

    Article  PubMed  CAS  Google Scholar 

  • Akbas E, Berber I (2005) Antibacterial and antifungal activities of new pyrazolo[3, 4-d]pyridazin derivatives. Eur J Med Chem 40:401–405

    Article  PubMed  CAS  Google Scholar 

  • Al-Allaf TAK, Rashan LJ (2001) Cis- and trans-platinum and palladium complexes: a comparative study review as antitumor agents. Boll Chim Farm 140:205–210

    PubMed  CAS  Google Scholar 

  • Al-Allaf TAK, Al-Bayati RH, Khalaf SH (1993) Synthesis and spectroscopic studies on organotin(IV) complexes of some pyrazoles and pyrazol-5-ones and their antibacterial activity. Appl Organomet Chem 7:635–640

    Article  CAS  Google Scholar 

  • Bauer VJ, Dalalian HP, Fanshawe WJ, Safir SR, Tocus EC, Boshart CR (1968) 4-[3(5)-pyrazolyl]pyridinium salts. A new class of hypoglycemic agents. J Med Chem 11:981–984

    Article  PubMed  CAS  Google Scholar 

  • Bebernitz GR, Argentieri G, Battle B, Brennan C, Balkan B, Burkey BF, Eckhardt M, Gao J, Kapa P, Strohschein RJ, Schuster HF, Wilson M, Xu DD (2001) The effect of 1, 3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob mice. J Med Chem 44:2601–2611

    Article  PubMed  CAS  Google Scholar 

  • Bekhit AA, Fahmy HTY, Rostom SAF, Baraka AM (2003) Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial agents. Eur J Med Chem 38:27–36

    Google Scholar 

  • Bekhit AA, Ashour HMA, Guemei AA (2005) Novel pyrazole derivatives as potential promising anti-inflammatory antimicrobial agents. Arch Pharm 338:167–174

    Article  CAS  Google Scholar 

  • Bekhit AA, Abdel-Rahman HM, Guemei AA (2006) Synthesis and biological evaluation of some hydroxypyrazole derivatives as anti-inflammatory-antimicrobial agents. Archiv der Pharmazie 339:81–87

    Google Scholar 

  • Bildirici I, Sener A, Tozlu I (2007) Further derivatives of 4-benzoyl-1, 5-diphenyl-1Hpyrazole-3-carboxylic acid and their antibacterial activities. Med Chem Res 16:418–426

    Article  CAS  Google Scholar 

  • Biot IC, Glorian G, Maciejewski L, Brocard L, Domarle O, Blampaim G, Millet P, Georges AJ, Abesolo H, Dive O, Lebibi J (1997) Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene–chloroquine analogue. J Med Chem 40:3715–3718

    Article  PubMed  CAS  Google Scholar 

  • Blomstrand R (1972) In: Akeson A, Ehrenberg A (eds) Structure and function of oxidation–reduction enzymes. Pergamon, Oxford, pp 667–679

  • Blomstrand R, Ostling-Wintzell H, Lof A, McMartin K, Tolf B, Hedstrom K (1979) Pyrazoles as inhibitors of alcohol oxidation and as important tools in alcohol research: an approach to therapy against methanol poisoning. Proc Natl Acad Sci USA 76:3499–3503

    Article  PubMed  CAS  Google Scholar 

  • Braddock PD, Connors TA, Jones M, Khokhar AR, Melzack DH, Tobe ML (1975) Structure and activity relationships of platinum complexes with anti-tumour activity. Chem-Biol Interact 11:145–161

    Article  PubMed  CAS  Google Scholar 

  • Bravi G, Corfield JA, Grimes RM, Guidetti R, Lovegrove VLH, Mordaunt JE, Shah P, Slater MJ (2005) 4-Carboxpyrazole derivatives useful as antivirals agents. Pat. No. WO/2005/092863

  • Broomhead JA, Rendina I, Sterns M (1992) Dinuclear complexes of platinum with the 4,4′-dipyrazolylmethane ligand. Synthesis, characterization, and x-ray crystal structure of.gamma.-bis(4,4′-dipyrazolylmethane-N,N′)bis[dichloroplatinum(II)]-N,N-dimethylformamide (1/2) and related complexes. Inorg Chem 31:1880–1889

    Article  CAS  Google Scholar 

  • Broomhead JA, Rendina I, Webster LK (1993) Dinuclear complexes of platinum having anticancer properties. DNA-binding studies and biological activity of Bis(4,4′-dipyrazolylmethane-N,N′)-bis[dichloroplatinum(II)] and related complexes. J Inorg Biochem 49:221–234

    Article  PubMed  CAS  Google Scholar 

  • Broomhead JA, Camm G, Sterns M, Webster L (1998) Dinuclear complexes of first transition series metals with 4,4′-dipyrazolylmethane: characterisation, DNA binding and anticancer properties. Inorg Chim Acta 271:151–159

    Article  CAS  Google Scholar 

  • Budakoti A, Abid M, Azam A (2007) Syntheses, characterization and in vitro antiamoebic activity of new Pd(II) complexes with 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives. Eur J Med Chem 42:544–551

    Article  PubMed  CAS  Google Scholar 

  • Budzisz E, Malecka M, Nawrot B (2004a) Synthesis and structure of highly substituted pyrazole ligands and their complexes with platinum(II) and palladium(II) metal ions. Tetrahedron 60:1749–1759

    Article  CAS  Google Scholar 

  • Budzisz E, Krajewska U, Rozalski M, Szulawska A, Czyz M, Nawrot B (2004b) Biological evaluation of novel Pt(II) and Pd(II) complexes with pyrazole-containing ligands. Eur J Pharmacol 502:59–65

    Article  PubMed  CAS  Google Scholar 

  • Budzisz E, Miernicka M, Lorenz I-P, Mayer P, Krajewska U, Rozalski M (2009) Synthesis and X-ray structure of platinum(II), palladium(II) and copper(II) complexes with pyridine–pyrazole ligands: influence of ligands’ structure on cytotoxic activity. Polyhedron 28:637–645

    Article  CAS  Google Scholar 

  • Burguete A, Pontiki E, Hadjipavlou-Litina D, Villar R, Vicente E, Solano B, Ancizu S, Perez-Silanes S, Aldana I, Monge A (2007) Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. Bioorg Med Chem Lett 17:6439–6443

    Google Scholar 

  • Carabateas PM, Diana GD (1980) Antiviral arylenedioxyalkyl substituted pyrazoles. Pat. No. 06/008412

  • Casas JS, Castellano EE, Ellena J, García-Tasende MS, Pérez-Parallé ML, Sánchez A, Sánchez-González A, Sordo J, Touceda A (2008) New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity. J Inorg Biochem 102:33–45

    Article  PubMed  CAS  Google Scholar 

  • Chande MS, Thakkar NV, Patil DV (1999) Synthesis and antimicrobial activity of bis[6-phenyl-4-methyl-3-substituted-pyrazo[4,5-d]pyrazol-1-yl]thioketones. Drug Res 56:207–210

    CAS  Google Scholar 

  • Ciesielska E, Szulawska A, Studzian K, Ochocki J, Malinowska K, Kik K, Szmigiero L (2006) Comparative studies on the mechanism of cytotoxic action of novel platinum II complexes with pyrazole ligands. J Inorg Biochem 100:1579–1585

    Article  PubMed  CAS  Google Scholar 

  • Comber RN, Gray RJ, Secrist JA III (1991) Acyclic analogues of pyrazofurin: syntheses and antiviral evaluation. Carbohydr Res 216:441–452

    Article  PubMed  CAS  Google Scholar 

  • Dahlbom R, Tolf BR, Akeson A, Lundquist G, Theorell H (1974) On the inhibitory power of some further pyrazole derivatives of horse liver alcohol dehydrogenase. Biochem Biophys Res Commun 57:549–5353

    Article  PubMed  CAS  Google Scholar 

  • Damljanovic I, Vukicevic M, Radulovic N, Palic R, Ellmerer E, Ratkovic Z, Joksovic MD, Vukicevic RD (2009) Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit. Bioorg Med Chem Lett 19:1093–1096

    Article  PubMed  CAS  Google Scholar 

  • Di Parsia MT, Suarez C, Vitolo MJ, Marquez VE, Beyer B, Urbina C, Hurtado I (1981) Synthesis and study of the potential antiallergic activity of some pyrazole derivatives. J Med Chem 24:117–119

    Article  PubMed  CAS  Google Scholar 

  • Dias HVR, Batdorf KH, Fianchini M, Diyabalanage HVK, Carnahan S, Mulcahy R, Rabiee A, Nelson K, van Waasbergen LG (2006) Antimicrobial properties of highly fluorinated silver(I) tris(pyrazolyl)borates. J Inorg Biochem 100:158–160

    Article  PubMed  CAS  Google Scholar 

  • Ding L, Grehn L, De Clercq E, Andrei G, Snoeck R, Balzarini J, Fransson B, Ragnarsson U (1989) Synthesis and antiviral activity of three pyrazole analogues of distamycin A. Acta Chem Scand (Copenhagen, Denmark) 48:498–505

    Google Scholar 

  • Dombrowski KE, Baldwin W, Sheats JE (1986) Metallocenes in biochemistry, microbiology & medicine. J Organomet Chem 302:281–306

    Article  CAS  Google Scholar 

  • Duivenvoorden WCM, Liu Y-N, Schatte G, Kraatz H-B (2005) Synthesis of redox-active ferrocene pyrazole conjugates and their cytotoxicity in human mammary adenocarcinoma MCF-7 cells. Inorg Chim Acta 358:3183–3189

    Article  CAS  Google Scholar 

  • Eklund H, Nordström B, Zeppezauer E, Söderlund G, Ohlsson I, Boiwe T, Söderberg BO, Tapia O, Brändén CI, Akeson A (1976) Three-dimensional structure of horse liver alcohol dehydrogenase at 2–4 Å resolution. J Mol Biol 102:27–59

    Article  PubMed  CAS  Google Scholar 

  • Eklund H, Samama J-P, Wallen L (1982) Pyrazole binding in crystalline binary and ternary complexes with liver alcohol dehydrogenase. Biochemistry 21:4858–4866

    Article  PubMed  CAS  Google Scholar 

  • El-Gaby MSA, Atalla AA, Gaber AM, Al-Wahab KAA (2000) Studies on aminopyrazoles: antibacterial activity of some novel pyrazolo[1, 5-a]pyrimidines containing sulfonamido moieties. Farmaco 55:596–602

    Article  PubMed  CAS  Google Scholar 

  • Elguero J, Goya P, Jagerovic N, Silva AMS (2002) Pyrazoles as drugs: facts and fantasies. Targets Heterocycl Syst 6:52–98

    CAS  Google Scholar 

  • El-Sabbagh OI, Baraka MM, Ibrahim SM, Pannecouque C, Andrei G, Snoeck R, Balzarini J, Rashad AA (2009) Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur J Med Chem 44:3746–3753

    Article  PubMed  CAS  Google Scholar 

  • Fang J, Jin Z, Li Z, Liu W (2003) Synthesis, structure and antibacterial activities of novel ferrocenyl-containing 1-phenyl-3-ferrocenyl-4-triazolyl-5-aryl-dihydropyrazole derivatives. J Organomet Chem 674:1–9

    Article  CAS  Google Scholar 

  • Farghaly AM, Soliman FSG, El Semary MMA, Rostom SAF (2001) Polysubstituted pyrazoles, part 4: synthesis, antimicrobial and anti-inflammatory activity of some pyrazoles. Pharmazie 56:28–32

    PubMed  CAS  Google Scholar 

  • Fonteh P, Keter FK, Meyer D, Guzei IA, Darkwa J (2009) Tetra-chloro-bis(3, 5-dimethylpyrazolylmethane)gold(III) chloride: an HIV-1 reverse transcriptase and protease inhibitor. J Inorg Biochem 103:190–194

    Article  PubMed  CAS  Google Scholar 

  • Gama S, Mendes F, Marques F, Santos IC, Carvalho MF, Correia I, Pessoa JC, Santos I, Paulo A (2011) Copper(II) complexes with tridentate pyrazole-based ligands: synthesis, characterization, DNA cleavage activity and cytotoxicity. J Inorg Biochem 105:637–644

    Article  PubMed  CAS  Google Scholar 

  • Gamage SA, Spicer JA, Rewcastle GW, Milton J, Sohal S, Dangerfield W, Mistry P, Vicker N, Charlton PA, Denny WA (2002) Structure–activity relationships for pyrido-, imidazo-, pyrazolo-, pyrazino-, and pyrrolophenazinecarboxamides as topoisomerase-targeted anticancer agents. J Med Chem 45:740–743

    Article  PubMed  CAS  Google Scholar 

  • Garg HG, Singhal A, Mathur JML (1973) Synthesis and biological activity of 1,5-diphenyl-4-arylazopyrazoles and 5,5-dimethylcyclohexane-1,2,3-trione-bishydrazones. J Pharm Sci 62:494–496

    Article  PubMed  CAS  Google Scholar 

  • Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RJ, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH (2000a) Substituent effects on the antibacterial activity of nitrogen–carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms haemophilus influenzae and moraxella catarrhalis. J Med Chem 43:953–970

    Article  PubMed  CAS  Google Scholar 

  • Genin MJ, Biles C, Keiser BJ, Poppe SM, Swaney SM, Tarpley WG, Yagi Y, Romero DL (2000b) Novel 1,5-Diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives. J Med Chem 43:1034–1040

    Article  PubMed  CAS  Google Scholar 

  • Graham J, Muhsin M, Kirkpatrick P (2004) Oxaliplatin. Nat Rev Drug Discov 3:11–12

    Article  PubMed  CAS  Google Scholar 

  • Haque TS, Tadesse S, Marcinkeviciene J, Rogers MJ, Sizemore C, Kopcho LM, Amsler K, Ecret LD, Zhan DL, Hobbs F, Slee A, Trainor GL, Stern AM, Copeland RA, Combs AP (2002) Parallel synthesis of potent, pyrazole-based inhibitors of helicobacter pylori dihydroorotate dehydrogenase. J Med Chem 45:4669–4678

    Article  PubMed  CAS  Google Scholar 

  • Harrap KR (1985) Preclinical studies identifying carboplatin as a viable cisplatin alternative. Cancer Treat Rev 12:21–23

    Article  PubMed  CAS  Google Scholar 

  • Hirschmann R, Buchschacher P, Steinberg NG, Fried JH, Ellis R, Kent GJ, Tishler M (1964) Synthesis and structure of steroidal Pregn-4-eno- and 5α-Pregnano [3,2-c]pyrazoles. A novel class of potent anti-inflammatory steroids. J Am Chem Soc 86:1520–1527

    Article  CAS  Google Scholar 

  • Johansson A, Poliakov A, Åkerblom E, Lindeberg G, Winiwarter S, Samuelsson B, Danielson UH, Hallberg A (2002) Tetrapeptides as potent protease inhibitors of hepatitis C virus full-length NS3 (protease–helicase/NTPase). Bioorg Med Chem 10:3915–3922

    Article  PubMed  CAS  Google Scholar 

  • Jungheim LN (1989) Bicyclic pyrazolidinone antibacterial agents. Synthesis of side chain analogues of carbapenems PS-5 and thienamycin. Tetrahedron Lett 30:1889–1892

    Article  CAS  Google Scholar 

  • Kaymakcıoglu BK, Rollas S (2002) Synthesis, characterization and evaluation of antituberculosis activity of some hydrazones. Il Farmaco 57:595–599

    Article  Google Scholar 

  • Kees KL, Fitzgerald JJ Jr, Steiner KE, Mattes JF, Mihan B, Tosi T, Mondoro D, McCaleb ML (1996) New potent antihyperglycemic agents in db/db mice: synthesis and structure–activity relationship studies of (4-substituted benzyl)(trifluoromethyl)pyrazoles and -pyrazolones. J Med Chem 39:3920–3928

    Article  PubMed  CAS  Google Scholar 

  • Kelland LR, Sharp SY, O’Neill CF, Raynaud FI, Beale PJ, Judson IR (1999) Mini-review: discovery and development of platinum complexes designed to circumvent cisplatin resistance. J Inorg Biochem 77:111–115

    Article  PubMed  CAS  Google Scholar 

  • Keter FK, Kanyanda S, Darkwa J, Rees DJG, Meyer M (2008) In vitro evaluation of dichloro-bis(pyrazole)palladium(II) and dichloro-bis(pyrazole)platinum(II) complexes as anticancer agents. Cancer Chemother Pharmacol 63:127–138

    Article  PubMed  CAS  Google Scholar 

  • Keter FK, Nell MJ, Omondi B, Guzei IA, Darkwa J (2009a) Anticancer activities of bis(pyrazol-1-ylthiocarbonyl)disulfides against HeLa cells. J Chem Res 5:322–325

    Article  Google Scholar 

  • Keter FK, Ojwach SO, Oyetunji OA, Guzei IA, Darkwa J (2009b) Bis(pyrazolyl) palladium(II), platinum(II) and gold(III) complexes: syntheses, molecular structures and substitution reactions with l-cysteine. Inorg Chim Acta 362:2595–2602

    Article  CAS  Google Scholar 

  • Kidani Y, Noji M, Tashiro T (1980) Antitumor activity of platinum(II) complexes of 1,2-diamino-cyclohexane isomers. Gann 71:637–643

    PubMed  CAS  Google Scholar 

  • Komeda S, Lutz M, Spek AL, Chikuma M, Reedijk J (2000) New antitumor-active azole-bridged dinuclear platinum(II) complexes: synthesis, characterization, crystal structures, and cytotoxic studies. Inorg Chem 39:4230–4236

    Article  PubMed  CAS  Google Scholar 

  • Kratz F, Nuber B, Weiss J, Keppler BK (1992) Synthesis and characterization of potential antitumour and antiviral gallium(III) complexes of N-heterocycles. Polyhedron 11:487–498

    Article  CAS  Google Scholar 

  • Kucukguzel SG, Rollas S, Erdeniz H, Kivaz M, Ekinci AC, Vidin A (2000) Synthesis, characterization and pharmacological properties of some 4-arylhydrazono-2-pyrazoline-5-one derivatives obtained from heterocyclic amines. Eur J Med Chem 35:761–771

    Article  CAS  Google Scholar 

  • Kulkarni NV, Revankar VK (2011) Synthesis, antimicrobial screening, and DNA-binding/cleavage of new pyrazole-based binuclear CoII, NiII, CuII, and ZnII complexes. J Coord Chem 64:725–741

    Article  CAS  Google Scholar 

  • La Colla P, Manfredini S, Simoni D, Baraldi PG, Pani A (1996) Pyrazole-related derivatives endowed with antitumor and antiviral activities, procedures for their preparation, pharmaceutical formulations containing them. Pat. No. WO/1996/040704

  • Li TK, Theorell H (1969) Human liver alcohol dehydrogenase: inhibition by pyrazole and pyrazole analogs. Acta Chem Scand 23:892–902

    Article  PubMed  CAS  Google Scholar 

  • Li H, Nukui S, Scales SA, Teng’ M, Yin C (2010). Novel 3-aminopyrrolo[3,4-C]pyrazole-5(1H, 4H, 6H) carbaldehyde derivatives. Pat No. 20100130501

  • Li G, Fathi R, Yang Z, Liao Y, Zhu Q, Lam A, Sandrasagra A, Nawoschik K, Cho H-J, Cao J, Ruoqiu W, Wobbe CR, Liu Y (2011) 4-Ethnyl pyrazole derivative compounds and methods for treatment of HCV. Pat. No. US 7923004

  • Mahmud K, Khan MA, Iqbal MZ (2001) Antibacterial property of some transition metal complexes of pyrazole derivatives. Pak J Biol Sci 4:1000–1001

    Article  Google Scholar 

  • Manfredini S, Bazzanini R, Baraldi PG, Guarneri M, Simoni D, Marongiu ME, Pani A, La Colla P, Tramontano E (1992) Pyrazole-related nucleosides. Synthesis and antiviral/antitumor activity of some substituted pyrazole and pyrazolo[4,3-d]-1,2,3-triazin-4-one nucleosides. J Med Chem 35:917–924

    Article  PubMed  CAS  Google Scholar 

  • Manikannan R, Venkatesan R, Muthusubramanian S, Yogeeswari P, Sriram D (2010) Pyrazole derivatives from azines of substituted phenacyl aryl/cyclohexyl sulfides and their antimycobacterial activity. Bioorg Med Chem Lett 20:6920–6924

    Article  PubMed  CAS  Google Scholar 

  • Menozzi G, Mosti L, Fossa P, Mattioli F, Ghia M (1997) ω-Dialkylaminoalkyl ethers of phenyl-(5-substituted 1-phenyl-1H-pyrazol-4-yl)methanols with analgesic and anti-inflammatory activity. J Heterocycl Chem 34:963–968

    Google Scholar 

  • Mosoarca EM, Pantenburg I, Tudose R, Meyer G, Popa NC, Han A, Alexandrova R, Kalfin R, Linert W, Costisor O (2011) Synthesis, structure and cytotoxic activity of mixed-valent Cu(I)/Cu(II) salt containing a pyrazolone derivative as ligand. Inorg Chim Acta. doi:10.1016/j.ica.2011.02.035

    Google Scholar 

  • Moukha-chafiq O, Taha ML, Lazrek HB, Vasseur J–J, Pannecouque C, Witvrouw M, De Clercq E (2002) Synthesis and biological activity of some 4-substituted 1-[1-(2,3-dihydroxy-1-propoxy)methyl-1,2,3-triazol-(4&5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines. Farmaco 57:27–32

    Article  PubMed  CAS  Google Scholar 

  • Narlawar R, Baumann K, Schubenel R, Schmidt B (2007) Curcumin derivatives inhibit or modulate beta-amyloid precursor protein metabolism. Neurodegener Dis 4:88–93

    Article  PubMed  CAS  Google Scholar 

  • Narlawar R, Pickhardt M, Leuchtenberger S, Baumann K, Krause S, Dyrks T, Weggen S, Mandelkow E, Schmidt B (2008) Curcumin-derived pyrazoles Swiss army knives or blunt Alzheimer’s disease? ChemMedChem 3:165–172

    Article  PubMed  CAS  Google Scholar 

  • Negm NA, Said MM, Morsy SMI (2010) Pyrazole derived cationic surfactants and their tin and copper complexes: synthesis, surface activity, antibacterial and antifungal efficacy. J Surfactants Deterg 13:521–528

    Article  CAS  Google Scholar 

  • Nomiya K, Noguchi R, Ohsawa K, Tsuda K, Oda M (2000) Synthesis, crystal structure and antimicrobial activities of two isomeric gold(I) complexes with nitrogen-containing heterocycle and triphenylphosphine ligands, [Au(L)(PPh3)] (HL = pyrazole and imidazole). J Inorg Biochem 78:363–370

    Article  PubMed  CAS  Google Scholar 

  • Onoa GB, Moreno V, Font-Bardia M, Solans X, Pérez JM, Alonso C (1999) Structural and cytotoxic study of new Pt(II) and Pd(II) complexes with the bi-heterocyclic ligand mepirizole. J Inorg Biochem 75:205–212

    Article  PubMed  CAS  Google Scholar 

  • Ouyang G, Cai X-J, Chen Z, Song B-A, Bhadury PS, Yang S, Jin L-H, Xue W, Hu D-Y, Zeng S (2008) Synthesis and antiviral activities of pyrazole derivatives containing an oxime moiety. J Agric Food Chem 56:10160–10167

    Article  PubMed  CAS  Google Scholar 

  • Pancic F, Steinberg BA, Diana GD, Carabateas PM, Gorman WG, Came PE (1981) Antiviral activity of Win 41258-3, a pyrazole compound, against herpes simplex virus in mouse genital infection and in guinea pig skin infection. Antimicrob Agents Chemother 19:470–476

    PubMed  CAS  Google Scholar 

  • Panda J, Srinivas SV, Rao ME (2002) Synthesis and antimicrobial activity of some pyrazoline derivatives of 4(3H)-quinazolinones. J Indian Chem Soc 79:770–776

    CAS  Google Scholar 

  • Park H-J, Lee K, Park S-J, Ahn B, Lee J-C, Cho HY, Lee K-I (2005) Identification of antitumor activity of pyrazole oxime ethers. Bioorg Med Chem Lett 15:3307–3312

    Article  PubMed  CAS  Google Scholar 

  • Pereira EF, Aracava Y, Aronstam RS, Barreiro EJ, Albuquerque EXJ (1992) Pyrazole, an alcohol dehydrogenase inhibitor, has dual effects on N-methyl-d-aspartate receptors of hippocampal pyramidal cells: agonist and noncompetitive antagonist. Pharmacol Exp Ther 261:331–340

    CAS  Google Scholar 

  • Pettinari C, Caruso F, Zaffaroni N, Villa R, Marchetti F, Pettinari R, Phillips C, Tanski J, Rossi M (2006) Synthesis, spectroscopy (IR, multinuclear NMR, ESI-MS), diffraction, density functional study and in vitro antiproliferative activity of pyrazole-beta-diketone dihalotin(IV) compounds on 5 melanoma cell lines. J Inorg Biochem 100:58–69

    Article  PubMed  CAS  Google Scholar 

  • Pinto DCGA, Silva AMS, Cavaleiro JAS, Foces-Foces C, Llamas-Saiz AL, Jagerovic N, Elguero J (1999) Synthesis and molecular structure of 3-(2-benzyloxy-6-hydroxyphenyl)-5-styrylpyrazoles. Reaction of 2-styrylchromones and hydrazine hydrate. Tetrahedron 55:10187–10200

    Article  CAS  Google Scholar 

  • Radi S, Salhi S, Radi A (2010) Synthesis and preliminary biological activity of some new pyrazole derivatives as acyclonucleoside analogues. Lett Drug Des Discov 7:27–30

    Article  CAS  Google Scholar 

  • Rathelot P, Azas N, El-Kashef H, Delmas F, Di Giorgio C, Timon-David P, Maldonado J, Vanelle P (2002) 1,3-Diphenylpyrazoles: synthesis and antiparasitic activities of azomethine derivatives. Eur J Med Chem 37:671–679

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg B, van Camp L, Krigas T (1965) Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205:698–699

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg B, van Camp L, Trosko JE, Mansour VH (1969) Platinum compounds: a new class of potent antitumour agents. Nature (London) 222:385–386

    Article  CAS  Google Scholar 

  • Rostom SAF, Shalaby MA, El-Demellawy MA (2003) Polysubstituted pyrazoles, part 5. Synthesis of new 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived ring systems. A novel class of potential antitumor and anti-HCV agents. Eur J Med Chem 38:959–974

    Article  PubMed  CAS  Google Scholar 

  • Russell AD, Hugo WB (1994) Antimicrobial activity and action of silver. Prog Med Chem 31:351–370

    Article  PubMed  CAS  Google Scholar 

  • Sakai K, Tomista Y, Ue T, Goshima K, Ohminato M, Tsubomura T, Matsumoto K, Ohmura K, Kawakami K (2000) Syntheses, antitumor activity, and molecular mechanics studies of cis-PtCl2(pzH)2 (pzH=pyrazole) and related complexes. Crystal structure of a novel Magnus-type double-salt [Pt(pzH)4][PtCl4][cis-PtCl2(pzH)2]2 involving two perpendicularly aligned 1D chains. Inorg Chim Acta 297:64–71

    Article  CAS  Google Scholar 

  • Sau DK, Butcher RJ, Chaudhuri S, Saha N (2003) Spectroscopic, structural and antibacterial properties of copper(II) complexes with bio-relevant 5-methyl-3-formylpyrazole N(4)-benzyl-N(4)-methylthiosemicarbazone. Mol Cell Biochem 253:21–29

    Article  PubMed  CAS  Google Scholar 

  • Segapelo TV, Guzei IA, Spencer LC, Van Zyl WE, Darkwa J (2009) (Pyrazolylmethyl)pyridine platinum(II) and gold(III) complexes: synthesis, structures and evaluation as anticancer agents. Inorg Chim Acta 362:3314–3324

    Article  CAS  Google Scholar 

  • Sharma KV, Sharma V, Tripathi UN (2009) Synthesis, spectroscopic, antibacterial and antifungal studies of nickel(II)5(2′-hydroxyphenyl)-3-(4-X-phenyl)pyrazolinates and their addition complexes with N and P donor ligands. J Coord Chem 62:676–690

    Article  CAS  Google Scholar 

  • Shen D-M, Shu M, Mills SG, Chapman KT, Malkowitz L, Springer MS, Gould SL, DeMartino JA, Siciliano SJ, Kwei GY, Carella A, Carver G, Holmes K, Schleif WA, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller MD, Emini EA (2004a) Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: discovery and SAR study of 4-pyrazolylpiperidine side chains. Bioorg Med Chem Lett 14:935–939

    Article  PubMed  CAS  Google Scholar 

  • Shen D-M, Shu M, Willoughby CA, Shah S, Lynch CL, Hale JJ, Mills SG, Chapman KT, Malkowitz L, Springer, Gould SL, DeMartino JA, Siciliano SJ, Lyons K, Pivnichny JV, Kwei GY, Carella A, Carver G, Holmes K, Schleif WA, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller MD, Emini EA (2004b) Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 2: Discovery of potent, selective, and orally bioavailable compounds. Bioorg Med Chem Lett 14:941–945

    Article  PubMed  CAS  Google Scholar 

  • Shih SR, Chu TY, Reddy GR, Tseng SN, Chen HL, Tang WF, Wu MS, Yeh JY, Chao YS, Hsu JT, Hsieh HP, Horng JT (2010) Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity. J Biomed Sci 23:13–17

    Article  CAS  Google Scholar 

  • Shipps Jr GW, Curran PJ, Annis DA, Nash HM, Cooper AB, Zhu HY, Wang J J-S, Desai JA, Girijavallabhan V (2006a) Substituted5-carboxyamide pyrazoles and [1,2,4] triazoles as antiviral agents. Pat. No. WO/2006/050034

  • Shipps Jr GW, Wang T, Rosner KE, Curran PJ, Cooper AB, Girijavallabhan VM (2006b) Substituted 5-oxo pyrazoles and [1,2,4] triazoles as antiviral agents. Pat. No. US7115749

  • Stauffer SR, Coletta CJ, Tedesco R, Nishiguchi G, Carlson K, Sun J, Katzenellenbogen BS, Katzenellenbogen JA (2000) Pyrazole ligands: structure–affinity/activity relationships and estrogen receptor-α-selective agonists. J Med Chem 43:4934–4947

    Article  PubMed  CAS  Google Scholar 

  • Stauffer SR, Huang YR, Aron ZD, Coletta CJ, Sun J, Katzenellenbogen BS, Katzenellenbogen JA (2001) Triarylpyrazoles with basic side chains: development of pyrazole-based estrogen receptor antagonists. Bioorg Med Chem 9:151–161

    Article  PubMed  CAS  Google Scholar 

  • Storer R, Ashton CJ, Baxter AD, Hann MM, Marr CLP, Mason AM, Mo C-L, Myers PL, Noble SA, Penn CR, Weir NG, Woods JM, Coe PL (1999) The synthesis and antiviral activity of 4-fluoro-1-β-d-ribofuranosyl-1H-pyrazole-3-carboxamide. Nucleotides 18:203–216

    Article  CAS  Google Scholar 

  • Sweeney ZK, Harris SF, Arora N, Javanbakht H, Li Y, Fretland J, Davidson JP, Billedeau JR, Gleason SK, Hirschfeld D, Kennedy-Smith JJ, Mirzadegan T, Roetz R, Smith M, Sperry S, Suh JM, Wu J, Tsing S, Villasenor AG, Paul A, Su G, Heilek G, Hang JQ, Zhou AS, Jernelius JA, Zhang F-J, Klumpp K (2008) Design of annulated pyrazoles as inhibitors of HIV-1 reverse transcriptase. J Med Chem 51:7449–7458

    Article  PubMed  CAS  Google Scholar 

  • Takabatake E, Kodama R, Tanaka Y, Dohmori R, Tachizawa H, Naito T (1970) The metabolic fate of 1-(4-methoxy-6-methyl-2-pyrimidinyl)-3-methyl-5-methoxypyrazole (mepirizole, DA-398) in rats and rabbits. Chem Pharm Bull 18:1900–1907

    Article  PubMed  CAS  Google Scholar 

  • Tanitame A, Oyamada Y, Ofuji K, Fujimoto M, Iwai N, Hiyama Y, Suzuki K, Ito H, Terauchi H, Kawasaki M, Nagai K, Wachi M, Yamagishi J (2004) Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors. Pyrazole derivatives. J Med Chem 47:3693–3699

    Article  PubMed  CAS  Google Scholar 

  • Tharmaraj P, Kodimunthiri D, Sheela CD, Priya CS (2009) Synthesis, spectral studies and antibacterial activity of Cu(II), Co(II) and Ni(II) complexes of 1-(2-hydroxyphenyl)-3-phenyl-2-propan-1-one, N2-[(3,5-diemthyl-1H-pyrazol-1-yl)methyl]hydrazone. J Serb Chem Soc 74:927–938

    Article  CAS  Google Scholar 

  • Theorell H, Yonetani T (1963) Liver alcohol dehydrogenase-DPN-pyrazole complex: a model of a ternary intermediate in the enzyme reaction. Biochem Z 338:537–553

    PubMed  CAS  Google Scholar 

  • Theorell H, Yonetani T, Sjoberg B (1969) On the effects of some heterocyclic compounds on the enzymatic activity of liver alcohol dehydrogenase. Acta Chem Scand 23:255–260

    Article  PubMed  CAS  Google Scholar 

  • Tobe ML, Khokhar AR (1977) Structure, activity, reactivity and solubility relationships of platinum diamine complexes. J Clin Hematol Oncol 7:114–137

    CAS  Google Scholar 

  • Vitolo MJ, Marquez VE, Hurtado I (1978) trans-2,3b,4,5,7,8b,9,10-Octahydronaphtho[1,2-c:5,6-c']dipyrazole, a new orally active antiallergic compound. J Med Chem 21:692–694

    Google Scholar 

  • Wheate NJ, Collins JG (2003) Multi-nuclear platinum complexes as anti-cancer drugs. Coord Chem Rev 241:133–145

    Article  CAS  Google Scholar 

  • Wheate NJ, Cullinane C, Webster LK, Collins JG (2001) Synthesis, cytotoxicity, cell uptake and DNA interstrand cross-linking of 4,4-dipyrazolylmethane-linked multinuclear platinum anti-cancer complexes. Anticancer Drug Des 16:91–98

    PubMed  CAS  Google Scholar 

  • Wu L, Song B, Bhadury PS, Yang S, Hu D, Jin L (2011) Synthesis and antiviral activity of novel pyrazole amides containing α-aminophosphonate moiety. J Heterocycl Chem 48:389–396

    Article  CAS  Google Scholar 

  • Zhang Y, Zhang L, Liu L, Guo J, Wu D, Xu G, Wang X, Jia D (2010) Anticancer activity, structure, and theoretical calculation of N-(1-phenyl-3-methyl-4-propyl-pyrazolone-5)-salicylidene hydrazone and its copper(II) complex. Inorg Chim Acta 363:289–293

    Article  CAS  Google Scholar 

  • Zhou H-B, Sheng S, Compton DR, Kim Y, Joachimiak A, Sharma S, Carlson KE, Katzenellenbogen BS, Nettles KW, Greene GL, Katzenellenbogen JA (2007) Structure-guided optimization of estrogen receptor binding affinity and antagonist potency of pyrazolopyrimidines with basic side chains. J Med Chem 50:399–403

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors would like to acknowledge Mintek and University of Johannesburg for support for some of the work cited in this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frankline K. Keter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keter, F.K., Darkwa, J. Perspective: the potential of pyrazole-based compounds in medicine. Biometals 25, 9–21 (2012). https://doi.org/10.1007/s10534-011-9496-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-011-9496-4

Keywords

Navigation