Cancers are already placing an enormous load on the worldwide healthcare practice; so, anti-neoplastic compounds nowadays are most essential in cancer remedy. Nevertheless, the expanding resistance in drug profiles’ appearance in recently available anticancer drugs has so far risen to a distressing level over past decades. Pyrazolone holds wideranging chemotherapeutic characteristics, including anticancer activity, and they inhabit a significant place in the novel drug development process. As per the literature, various hybridized pyrazolone moieties with different pharmacophores and pyrazolone metal complexes have anticancer activities with good potency. In recent years, pyrazolone hybrids and metal complexes were generated to study their anticancer properties. Out of these, some derivatives displayed promising strengths against the case of resistant and susceptible cell lines of cancer. This current review encloses the latest advances of pyrazolone hybrids including thiophene, aminomethylidenes , naphthoquinones, combretastatins, 2-substituted-4-(2-fluorophenoxy) pyridine, hydroxybenzo[a]phenazine, coumarin, dihydrobenzoxepine, cyclic peptide, cambinol derivatives of pyrazolone, and different metal complexes as a potential anticancer agent.
Adhikari S, Singh M, Sharma P, Arora S. Pyrazolones as potential anticancer scaffold: Recent trends and future perspectives. J Appl Pharm Sci, 2021; 11 (Supp 1):026–037.
Ahsan MJ, Samy JG, Jain CB, Dutt KR, Khalilullah H, Nomani MS. Discovery of novel anti-tubercular 1,5-dimethyl-2-phenyl-4-([5- (arylamino)-1,3,4-oxadiazol-2-yl]methylamino)-1,2-dihydro-3H-pyrazol3-one analogues. Bioorg Med Chem Lett, 2012; 22:969-72. https://doi.org/10.1016/j.bmcl.2011.12.014 | |
Akcha S, Gómez-Ruiz S, Kellou-Tairi S, Lezama L, Pérez FB, Benali-Baitich O. Synthesis, characterization, solution equilibria, DFT study, DNA binding affinity and cytotoxic properties of a cobalt(II) complex with a 5-pyrazolone ligand. Inorg Chim Acta, 2018; 482: 738-48. https://doi.org/10.1016/j.ica.2018.06.051 | |
Akondi AM, Kantam ML, Trivedi R, Bharatam J, Vemulapalli SPB, Bhargava SK, Prakasham RS. Ce/SiO2 composite as an efficient catalyst for the multicomponent one-pot synthesis of substituted pyrazolones in aqueous media and their antimicrobial activities. J Mol Catal A Chem, 2016; 411:325-36. https://doi.org/10.1016/j.molcata.2015.11.004 | |
Bae M, Oh J, Bae ES, Oh J, Hur J, Suh YG, Lee SK, Shin J, Oh DC. WS9326H, an antiangiogenic pyrazolone-bearing peptide from an intertidal mudflat actinomycete. Org Lett, 2018; 20:1999-02. https://doi.org/10.1021/acs.orglett.8b00546 | |
Bakr EA, Al-Hefnawy GB, Awad MK, Abd-Elatty HH, Youssef MS. New Ni(II), Pd(II) and Pt(II) complexes coordinated to azo pyrazolone ligand with a potent anti-tumor activity: synthesis, characterization, DFT and DNA cleavage studies. Appl Organomet Chem, 2017; 32:4104-7. Brogden RN. Pyrazolone derivatives. Drugs, 1986; 32:60-70. https://doi.org/10.1002/aoc.4104 | |
Brune K. The early history of non-opioid analgesics. Acute Pain, 1997; 1:33-40. https://doi.org/10.1016/S1366-0071(97)80033-2 | |
Burja B, ÄŒimbora-Zovko T, Tomić S, Jelušić T, KoÄevar M, Polanc S, Osmak M. Pyrazolone-fused combretastatins and their precursors: synthesis, cytotoxicity, antitubulin activity and molecular modeling studies. Bioorg Med Chem, 2010; 18:2375-87. https://doi.org/10.1016/j.bmc.2010.03.006 | |
Caruso F, Monti E, Matthews J, Rossi M, Gariboldi MB, Pettinari C, Pettinari R, Marchetti F. Synthesis, characterization, and antitumor activity of water-soluble (Arene)ruthenium(II) derivatives of 1,3-Dimethyl-4-acylpyrazolon-5-ato ligands. first example of Ru(arene) (ligand) antitumor species involving simultaneous Ru-N7(guanine) bonding and ligand intercalation to DNA. Inorg Chem, 2014; 53:3668-77. https://doi.org/10.1021/ic403170y | |
Casas JS, Castellano EE, Ellena J, García-Tasende MS, PérezParallé ML, Sánchez A, Sánchez-González Á, Sordo J, Touceda Á. 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, 2008; 102:33-45. https://doi.org/10.1016/j.jinorgbio.2007.06.032 | |
Counihan JL, Grossman EA, Nomura DK. Cancer metabolism: current understanding and therapies. Chem Rev, 2018; 118:6893-23. https://doi.org/10.1021/acs.chemrev.7b00775 | |
Cutsem, EV, Karaszewska, B, Kang, YK, Chung, HV, Shankaran, V, Siena, S, Go, NF, Yang, H, Schupp, M, Cunningham, D. A multicenter phase II study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other MET-amplified solid tumors. Clin Cancer Res, 2019; 25:1445-56. https://doi.org/10.1158/1078-0432.CCR-18-1337 | |
De Pascali SA, Migoni D, Monari M, Pettinari C, Marchetti F, Muscella A, Fanizzi FP. Synthesis, crystal structure, and biological study of PtII complexes with 4-Acyl-5-pyrazolones. Eur J Inorg Chem, 2014; 7:1249-59. https://doi.org/10.1002/ejic.201301479 | |
Deshmukh P, Soni PK, Kankoriya A, Halve AK, Dixit R. 4-Aminoantipyrine: a significant tool for the synthesis of biologically active schiff bases and metal complexes. Int J Pharma Sci Rev Res, 2015; 34:162-70. | |
Gaber M, Khedr AM, Mansour MA, Elsharkawy M. Nanosynthesis, characterization, modeling and molecular docking analysis of Mn (II), Co (II), Cr (III) and Cu (II) complexes with azo pyrazolone ligand as new favourable antimicrobial and antitumor agents. Appl Organomet Chem, 2018; 1:4606-8. https://doi.org/10.1002/aoc.4606 | |
Gao F, Zhang X, Wang TF, Xiao JQ. Quinolone hybrids and their anti-cancer activities: an overview. Eur J Med Chem, 2019; 165:59-79. https://doi.org/10.1016/j.ejmech.2019.01.017 | |
Ghorab MM, El-Gazzar MG, Alsaid MS. Synthesis, characterization and anti-breast cancer activity of new 4-aminoantipyrinebased heterocycles. Int J Mol Sci, 2014; 15:7539-53. https://doi.org/10.3390/ijms15057539 | |
Gouda MA, Eldien HF, Girges MM, Berghot MA. Synthesis and antitumor evaluation of thiophene based azo dyes incorporating pyrazolone moiety. J Saudi Chem Soc, 2016; 20:151-57. https://doi.org/10.1016/j.jscs.2012.06.004 | |
Gouhar, RS, Fathalla OA, Abd El-Karim SS. Synthesis and anticancer screening of some novel substituted pyrazole derivatives. Der Pharma Chem, 2013; 5:225-33 | |
Gu W, Dai Y, Qiang H, Shi W, Liao C, Zhao F, Huang W. Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor tyrosine kinase inhibitors. Bioorg Chem, 2017; 72:116-22. https://doi.org/10.1016/j.bioorg.2017.04.001 | |
Islam MS, Wang CY, Zheng JY, Paudyal N, Zhu YL, Sun HX. The potential role of tubeimosides in cancer prevention and treatment. Eur J Med Chem, 2019; 162:109-21. https://doi.org/10.1016/j.ejmech.2018.11.001 | |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Tumor J Clin, 2011; 61:69-90. https://doi.org/10.3322/caac.20107 | |
Kandhasamy S, Ramanathan G, Muthukumar T, Thyagarajan S, Umamaheshwari N, Santhanakrishnan VP, Sivagnanam UT, Perumal PT. Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics. Mat Sci Eng, 2017; 74:70-5. https://doi.org/10.1016/j.msec.2017.01.001 | |
Katritzky AR, Rees CW, Scriven EF. Comprehensive heterocyclic chemistry II. 5th edition, Pergamon, Oxford, UK, pp 301-9, 1996. | |
Kavitha Rani PR, Sheena Mary Y, Fernandez A, Anu Priya S, Shyma Mary Y, Thomas R. Single-crystal XRD, DFT investigations and molecular docking study of 2-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro1H-pyrazol-4-yl)amino)naphthalene-1,4-dione as a potential anti-cancer lead molecule. Comput Biol Chem, 2018, 78:153-64. https://doi.org/10.1016/j.compbiolchem.2018.11.022 | |
Kulkarni RC, Madar JM, Shastri SL, Shaikh F, Naik NS, Chougale RB, Shastri LA, Joshi SD, Dixit SR, Sunagar VA. Green synthesis of coumarin-pyrazolone hybrids: in vitro anticancer and anti-inflammatory activities and their computational study on COX-2 enzyme. Chem Data Collect, 2018; 17:497-06. https://doi.org/10.1016/j.cdc.2018.11.004 | |
Li Y, Zhao J, He CC, Zhang L, Sun SR, Xu GC. Synthesis, crystal structure and biological activity of two Mn complexes with 4-acyl pyrazolone derivatives. J Inorg Biochem, 2015; 150:28-7. https://doi.org/10.1016/j.jinorgbio.2015.06.003 | |
Lunagariya MV, Thakor KP, Kanthecha DN, Patel MN. Synthesis, characterization and biological applications of substituted pyrazolone corebased platinum(II) organometallic compounds. J Organomet Chem, 2018; 854:49-3. https://doi.org/10.1016/j.jorganchem.2017.11.012 | |
Mahajan SS, Scian M, Sripathy S, Posakony J, Lao U, Loe TK, Leko V, Thalhofer A, Schuler AD, Bedalov A, Simon JA. Development of pyrazolone and isoxazol-5-one cambinol analogues as sirtuin inhibitors. J Med Chem, 2014; 57:3283-94. https://doi.org/10.1021/jm4018064 | |
Mariappan G, Saha BP, Sutharson L, Singh A, Garg S, Pandey L, Kumar D. Analgesic, anti-inflammatory, antipyretic and toxicological evaluation of some newer 3-methyl pyrazolone derivatives. Saudi Pharm J, 2011; 19:115-22. https://doi.org/10.1016/j.jsps.2011.01.003 | |
Marković V, Erić S, Stanojković T, Gligorijević N, Aranđelović S, Todorović N, Trifunović S, Manojlović N, Jelić R, Joksović MD. Antiproliferative activity and QSAR studies of a series of new 4-aminomethylidene derivatives of some pyrazol-5-ones. Bioorg Med Chem Lett, 2011; 21:4416-21. https://doi.org/10.1016/j.bmcl.2011.06.025 | |
Metwally, NH, Mohamed, MS, Ragb, EA. Design, synthesis, anticancer evaluation, molecular docking and cell cycle analysis of 3-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine derivatives as potent histone lysine demethylases (KDM) inhibitors and apoptosis inducers. Bioorg Chem, 2019; 88:1029-32. https://doi.org/10.1016/j.bioorg.2019.102929 | |
Modi JS, Kulkarni MV. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: medicinal chemistry perspective. Med Drug Discov, 2019; 2:100009-11. https://doi.org/10.1016/j.medidd.2019.100009 | |
Montana M, Mathias F, Terme T, Vanelle P. Antitumoral activity of quinoxaline derivatives: a systematic review. Eur J Med Chem, 2019; 163:136-47. https://doi.org/10.1016/j.ejmech.2018.11.059 | |
Mosoarca EM, Pantenburg I, Tudose R, Meyer G, Popa NC, Han A, Alexandrova R, Kalfin R, Linert W, Costisor O. Synthesis, structure and cytotoxic activity of mixed-valent Cu(I)/Cu(II) salt containing a pyrazolone derivative as a ligand. Inorg Chim Acta, 2011; 370:460-68. https://doi.org/10.1016/j.ica.2011.02.035 | |
Mu LM, Ju RJ, Liu R, Bu YZ, Zhang JY, Li XQ, Zeng F, Lu WL. Dual-functional drug liposomes in the treatment of resistant cancers. Adv Drug Deliv Rev, 2017; 115:46-6. https://doi.org/10.1016/j.addr.2017.04.006 | |
Narayana Rao DV, Raghavendra Guru Prasad A, Spoorthy YN, Raghunatha Rao D, Ravindranath L K. In vitro microbiological evaluation of novel bis pyrazolones. Ann Pharmacol Franç, 2014; 72:101-6. https://doi.org/10.1016/j.pharma.2013.11.005 | |
Parmar N, Teraiya S, Patel R, Barad H, Jajda H, Thakkar V. Synthesis, antimicrobial and antioxidant activities of some 5-pyrazolone based Schiff bases. J Saudi Chem Soc, 2015; 19:36-1. https://doi.org/10.1016/j.jscs.2011.12.014 | |
Paulpandiyan R, Raman N. DNA binding propensity and nuclease efficacy of bio sensitive Schiff base complexes containing pyrazolone moiety: synthesis and characterization. J Mol Struct, 2016; 1125:374-82. https://doi.org/10.1016/j.molstruc.2016.07.003 | |
Pettinari R, Marchetti F, Di Nicola C, Pettinari C, Galindo A, Petrelli R, Cappellacci L, Cuccioloni M, Bonfili L, Eleuteri AM, Guedes da Silva MFC, Pombeiro AJL. Ligand design for N,O- or N, N-pyrazolonebased hydrazones ruthenium(II)-arene complexes and investigation of their anticancer activity. Inorg Chem, 2018; 57:14123-3. https://doi.org/10.1021/acs.inorgchem.8b01935 | |
Pettinari R, Marchetti F, Pettinari C, Petrini A, Scopelliti R, Clavel CM, Dyson PJ. Synthesis, structure, and antiproliferative activity of ruthenium(II) arene complexes with N,O-chelating pyrazolone-based β-Ketoamine ligands. Inorg Chem, 2014; 53:13105-11. https://doi.org/10.1021/ic502274b | |
Rashid H, Xu Y, Muhammad Y, Wang L, Jiang J. Research advances on anticancer activities of matrine and its derivatives: an updated overview. Eur J Med Chem, 2019; 161:205-38. https://doi.org/10.1016/j.ejmech.2018.10.037 | |
Rizk HF, Ibrahim SA, El-Borai MA. Synthesis, dyeing performance on polyester fiber and antimicrobial studies of some novel pyrazolotriazine and pyrazolyl pyrazolone azo dyes. Arab J Chem, 2017; 10:3303-9. https://doi.org/10.1016/j.arabjc.2014.01.008 | |
Saad FA, El-Metwaly NM, Farghaly TA, El-Ghalban MG, AlHazmi GA, Saleh KA, Alfaifi MY. Illustration for series of new metal ion complexes extracted from pyrazolone derivative, spectral, thermal, QSAR, DFT/B3LYP, docking, and antitumor investigations. J Mol Liq, 2016; 229:614-27. https://doi.org/10.1016/j.molliq.2016.11.035 | |
Saidachary G, Veera Prasad K, Divya D, Singh A, Ramesh U, Sridhar B, China Raju B. Convenient one-pot synthesis, anti-mycobacterial and anticancer activities of novel benzoxepinoisoxazolones and pyrazolones. Eur J Med Chem, 2014; 76:460-69. https://doi.org/10.1016/j.ejmech.2014.02.042 | |
Singh N, Krishnakumar S, Kanwar RK, Cheung CHA, Kanwar JR. Clinical aspects for surviving: a crucial molecule for targeting drugresistant cancers. Drug Discov Today, 2015; 20:578-87. https://doi.org/10.1016/j.drudis.2014.11.013 | |
Sivakumar KK, Rajasekaran A, Senthilkumar P, Wattamwar PP. Conventional and microwave-assisted synthesis of pyrazolone Mannich bases possessing anti-inflammatory, analgesic, ulcerogenic effect and antimicrobial properties. Bioorg Med Chem Lett, 2014; 24:2940-44. https://doi.org/10.1016/j.bmcl.2014.04.067 | |
Stornaiuolo M, La Regina G, Passacantilli S, Grassia G, Coluccia A, La Pietra V, Giustiniano M, Cassese H, Di Maro S, Brancaccio D, Taliani S. Structure-based lead optimization and biological evaluation of BAX direct activators as novel potential anticancer agents. J Med Chem, 2015; 58:2135-48. https://doi.org/10.1021/jm501123r | |
Tang, Y, Rong, X, Hu, W, Li, G, Yang, X, Yang, J, Xu, P, Luo, J. Effect of edaravone on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma after radiotherapy: a randomized controlled trial. J Neurooncol, 2014, 120:441-47. https://doi.org/10.1007/s11060-014-1573-4 | |
Tok F, KoçyiÄŸit-KaymakçıoÄŸlu B, Nurpelin SaÄŸlık B, Levent S, Özkay Y, Asım Kaplancıklı Z. Synthesis and biological evaluation of new pyrazolone schiff bases as monoamine oxidase and cholinesterase inhibitors. Bioorg Chem, 2019; 84:41-50. https://doi.org/10.1016/j.bioorg.2018.11.016 | |
Tripathy R, Ghose A, Singh J, Bacon ER, Angeles TS, Yang SX, Albom MS, Aimone LD, Herman JL, Mallamo JP. 1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors. Bioorg Med Chem Lett, 2007; 17:1793-98. https://doi.org/10.1016/j.bmcl.2006.12.054 | |
Tripathy R, McHugh RJ, Ghose AK, Ott GR, Angeles TS, Albom MS, Huang Z, Aimone LD, Cheng M, Dorsey BD. Pyrazolonebased anaplastic lymphoma kinase (ALK) inhibitors: control of selectivity by a benzyloxy group. Bioorg Med Chem Lett, 2011; 21:7261-64. https://doi.org/10.1016/j.bmcl.2011.10.055 | |
Tüzün, B. Investi̇gati̇on of pyrazoly derivatives schi̇ff base li̇gands and thei̇r metal complexes used as anti-cancer drug. Spectrochim Acta A Mol Biomol Spectrosc, 2019, 15; 11763-67 https://doi.org/10.1016/j.saa.2019.117663 | |
Vyas KM, Jadeja RN, Patel D, Devkar RV, Gupta VK. A new pyrazolone based ternary Cu (II) complex: Synthesis, characterization, crystal structure, DNA binding, protein binding and anti-cancer activity towards A549 human lung carcinoma cells with a minimum cytotoxicity to non-cancerous cells. Polyhedron, 2013, 28; 65:262-74. https://doi.org/10.1016/j.poly.2013.08.051 | |
Vyas KM, Jadeja RN, Patel D, Devkar RV, Gupta VK. Effect of ligand substitution in pyrazolone based binary and ternary Cu(II) complexes on DNA binding, protein binding and anti-cancer activity on A549 lung carcinoma cell lines. Polyhedron, 2014; 80:20-33. https://doi.org/10.1016/j.poly.2013.12.037 | |
Weast RC. Hand book of chemistry and physics. CRC Press Inc, Cleveland, Ohio, p 58, 1977. | |
Wiley R, Wiley P. Pyrazolones, pyrazolidones and derivatives: the chemistry of heterocyclic compounds. 20th edition, A Weissberger. Interscience Publishers, New York, NY, pp 1-12, 1964. https://doi.org/10.1002/9780470186817 | |
Yousuf S, Khan KM, Salar U, Chigurupati, S, Muhammad MT, Wadood A, Aldubayan M, Vijayan V, Riaz M, Perveen S. 2ʹ-Aryl and 4ʹ-arylidene substituted pyrazolones: as potential α-amylase inhibitors. Eur J Med Chem, 2018; 159:47-58. https://doi.org/10.1016/j.ejmech.2018.09.052 | |
Zhang Y, Zhang L, Liu L, Guo J, Wu D, Xu G, Wang X, Jia D. Anticancer activity, structure, and theoretical calculation of N-(1-phenyl3-methyl-4-propyl-pyrazolone-5)-salicylidene hydrazone and it's copper(II) complex. Inorganica Chim Acta, 2010; 363:289-93. https://doi.org/10.1016/j.ica.2009.08.017 | |
Zhao J, Zhang L, Li J, Wu T, Wang M, Xu G, Zhang F, Liu L, Yang J, Sun S. A novel pyrazolone-based derivative induces apoptosis in human esophageal cells via reactive oxygen species (ROS) generation and caspase-dependent mitochondria-mediated pathway. Chem Biol Interact, 2015; 231:1-9.https://doi.org/10.1016/j.cbi.2015.02.004 | |
Zhuang C, Guan X, Ma H, Cong H, Zhang W, Miao Z. Small molecule-drug conjugates: a novel strategy for cancer-targeted treatment. Eur J Med Chem, 2019; 163:883-95. https://doi.org/10.1016/j.ejmech.2018.12.035 | |
Zong Z, Wei X, Yan X, Fan Y.Crystal structures and anticancer activities of five novel pyrazolone-enamine transition metal complexes with 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one. J Mol Struct, 2018; 1171:333-39. https://doi.org/10.1016/j.molstruc.2018.06.019 |
Year
Month
Synthesis, Evaluation and Docking Study of 1, 3, 5-Triazine Derivatives as Cytotoxic Agents against Lung Cancer
Synthesis, characterization and anticancer studies of some morpholine derived Schiff bases and their metal complexes
Toxicity Testing of Tartrazine using the Nematode Caenorhabditis Elegans, Brine Shrimp Larvae (Artemia Salina) and KGN Granulosa Cell Line