Design, synthesis and cytotoxicity evaluation of pyrazolyl pyrazoline and pyrazolyl aminopyrimidine derivatives as potential anticancer agents
- 352 Downloads
In an attempt to find bio-active heterocyclic analogues, a series of novel 1-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazol-1-yl)ethanones 5a–i and 4-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-6-(pyridine-3-yl)pyrimidin-2-amines 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxicity against a panel of human cancer cell lines namely, HeLa (human cervix), NCI-H460 (human lung), PC-3 (human prostate), and NIH-3T3 (mouse embryo fibroblasts) cell lines. Most of these compounds exhibited moderate to good cytotoxicity against the tested cancer cell lines and weak toxicity against normal cell line. Analogs 5f, 5g, 5i, 6b–g showed significant cytotoxicity as compared to the standard drug etoposide. The compound 6g exhibited superior activity with IC50 value of 5.47 ± 0.44 µM against Hela cancer cell line.
KeywordsPyrazolylpyrazolines Pyrazolyl aminopyrimidines Michael addition Cytotoxicity MTT assay
The authors thank to the Head, Department of Chemistry, Jamia Millia Islamia, New Delhi for providing research facilities. AIRF, JNU is acknowledged for 13C NMR spectra. Raquib Alam is also thankful to UGC, New Delhi for BSR fellowship.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Acker TM, Khatri A, Vance KM, Slabber C, Bacsa J, Snyder JP, Traynelis SF, Liotta DC (2013) Structure-activity relationships and pharmacophore model of a noncompetitive pyrazoline containing class of GluN2C/GluN2D selective antagonists. J Med Chem 56:6434–6456CrossRefPubMedPubMedCentralGoogle Scholar
- Alam R, Alam MA, Panda AK, Rahisuddin (2017) Design, synthesis and cytotoxicity evaluation of 3-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine and 5-(3-(aryl)-1-phenyl-1h-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbaldehyde derivatives as potential anticancer agents. J Heterocycl Chem 54:1812–1821CrossRefGoogle Scholar
- Casimiro-Garcia A, Piotrowski DW, Ambler C, Arhancet GB, Banker ME, Banks T, Boustany-Kari CM, Cai C, Chen X, Eudy R, Hepworth D, Hulford CA, Jennings SM, Loria PM, Meyers MJ, Petersen DN, Raheja NK, Sammons M, She L, Song K, Vrieze D, Wei L (2014) Identification of (R)-6-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5-dihydro-1H-pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist. J Med Chem 57:4273–4288CrossRefPubMedGoogle Scholar
- Chen W, Ge X, Xu F, Zhang Y, Liu Z, Pan J, Song J, Dai Y, Zhou J, Feng J, Liang G (2015) Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury. Bioorg Med Chem Lett 25:2998–3004CrossRefPubMedGoogle Scholar
- Insuasty B, Tigreros A, Orozco F, Quiroga J, Abonia R, Nogueras M, Sanchez A, Cobo J (2010) Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents. Bioorg Med Chem 18:4965–4974CrossRefPubMedGoogle Scholar
- Meyers MJ, Arhancet GB, Hockerman SL, Chen X, Long SA, Mahoney MW, Rico JR, Garland DJ, Blinn JR, Collins JT, Yang S, Huang HC, McGee KF, Wendling JM, Dietz JD, Payne MA, Homer BL, Heron MI, Reitz DB, Hu X (2010) Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy. J Med Chem 53:5979–6002CrossRefPubMedGoogle Scholar
- Singh N, Pandey SK, Anand N, Dwivedi R, Singh S, Sinha SK, Chaturvedi V, Jaiswal N, Srivastava AK, Shah P, Siddiqui MI, Tripathi RP (2011) Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2-aminopyrimidines as antitubercular and antidiabetic agents. Bioorg Med Chem Lett 21:4404–4408CrossRefPubMedGoogle Scholar
- van Loevezijn A, Venhorst J, Iwema Bakker WI, de Korte CG, de Looff W, Verhoog S, van Wees JW, van Hoeve M, van de Woestijne RP, van der Neut MA, Borst AJ, van Dongen MJ, de Bruin NM, Keizer HG, Kruse CG (2011) N’-(arylsulfonyl)pyrazoline-1-carboxamidines as novel, neutral 5-hydroxytryptamine 6 receptor (5-HT6R) antagonists with unique structural features. J Med Chem 54:7030–7054CrossRefPubMedGoogle Scholar