Synthesis of novel α,α-difluoro-β-hydroxycarbonyl pyrazole derivatives as antioxidant, anti-inflammatory and anticancer agents

Abstract

A series of novel α,α-difluoro-β-hydroxyl pyrazole esters was prepared by Reformatsky reaction. Subsequently, these esters were converted to acids and hydrazides. All the synthesized compounds were evaluated for their in vitro antioxidant, anti-inflammatory and anticancer potential at various concentrations (50, 100 μM). Compounds 4d and 6e were found to be potent (93.19 and 90.91 %) and compounds 5d, 6c and 5f were good OH radical scavengers (79.55–72.73 %) as compared to the standard drug ascorbic acid (88.63 %). Compounds 6a, 5c, 6f, 4d and 5a showed significant 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (75.95–70.89 %). All the compounds have shown higher cyclooxygenase-1 (COX-1) inhibition over cyclooxygenase-2 (COX-2) at concentrations 100 and 50 μM. Compounds 5f, 6b, 4a, 5c, 4f, 5 and 6d showed significant COX-2 inhibition (38.56–28.30 %) at a concentration of 100 μM compared to standard drug aspirin (11.11 %). Compounds 6f, 6e and 5f have shown significant cytotoxicity against MCF-7 (51.03–40.59 %), whereas 6d, 5f and 5a showed moderate cytotoxicity against HL-60 (26.98–20.21 %) cancer cell lines compared to the methotrexate as reference standard (68.42 and 54.29 % respectively). All compounds have shown almost neglisible cytotoxicity against normal cell line 293.

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Correspondence to Hemant V. Chavan.

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Mukarram, S., Bandgar, B.P., Shaikh, R.U. et al. Synthesis of novel α,α-difluoro-β-hydroxycarbonyl pyrazole derivatives as antioxidant, anti-inflammatory and anticancer agents. Med Chem Res 26, 262–273 (2017). https://doi.org/10.1007/s00044-016-1744-2

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Keywords

  • Pyrazole
  • Reformatsky
  • Antioxidant
  • Anti-inflammatory
  • Anticancer