Synthesis, molecular docking, and evaluation of novel bivalent pyrazolinyl-1,2,3-triazoles as potential VEGFR TK inhibitors and anti-cancer agents

Original Paper
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Abstract

Investigations in the discovery of tyrosinase enzyme inhibitors have the potential to design novel anti-cancer drugs. A variety of novel bivalent pyrazolinyl triazoles 57 were synthesized and identified. The bis-acetyl triazole 3 was accomplished via two-step process first by preparation of diazide 2 followed its coupling reaction with acetylacetone in basic medium. The Claisen–Schmidt condensation reaction of 3 with two moles equivalent of benzaldehyde produces the corresponding bis-α, β-unsaturated ketone 4. Treatment of Schiff base 4 with excess hydrazine hydrate in either acetic acid or ethanol/DMF afforded the bis-N-acetylpyrazline 5 or bis-pyrazoline 6, respectively. Finally, treatment of 6 with two derivatives of isothiocyanate analog gives the bis-N-thioamide pyrazolines 7a and 7b. The synthesized compounds were evaluated as anti-tumor candidates against three human cancer cell lines (MCF-7, HepG2, and HCT-116). The bioscreening evaluation showed that compounds 7a and 6 had a significant antineoplastic potencies (IC50: 32.26 and 57.06 µg/mL) against breast MCF-7 and hepatic HepG2 cancerous cell lines, respectively, in relative to the standard drug, 5-fluorouracil. Molecular docking studies of the synthesized compounds were investigated as VEGFR2 TK inhibitors.

Graphical Abstract

Keywords

Bivalent ligands Pyrazoline Triazole VEGFR2 Computer-assisted molecular model Anti-cancer activity 

Supplementary material

11696_2018_451_MOESM1_ESM.docx (21 kb)
Appendix 1: Elemental analysis results of new compounds (DOCX 20 kb)
11696_2018_451_MOESM2_ESM.xls (42 kb)
Appendix 2: Checklist for compound characterizations (XLS 41 kb)

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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2018

Authors and Affiliations

  1. 1.Hormones Department, Medical Research DivisionNational Research CentreDokki, GizaEgypt
  2. 2.Applied Organic Chemistry DepartmentNational Research CentreDokki, GizaEgypt
  3. 3.Chemical Industries Research DivisionNational Research CentreDokki, CairoEgypt

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