Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents

Eur J Med Chem. 2013:70:740-9. doi: 10.1016/j.ejmech.2013.10.042. Epub 2013 Oct 30.

Abstract

N-(4-(Pyrazol-4-yl)thiazol-2-yl)-N'-phenylthiourea derivative 2 was synthesized and then treated with variety of hydrazonoyl chlorides under basic condition at reflux to afford the corresponding 2-(4-(pyrazol-4-yl)thiazol-2-ylimino)-1,3,4-thiadiazole derivatives 6, 10a-e and 17a-e. Reaction of 2 with ethyl chloroacetate and with 3-chloro-2,4-pentanedione gave the thiazolidin-4-one 22 and 1,3-thiazole 25 derivatives, respectively. Condensation of thiazolidin-4-one 22 with aldehydes gave their 5-arylidene derivatives 23a-f. Most of the synthesized compounds were tested for anticancer activity against human hepatocelluar carcinoma HepG2, human breast cancer MCF-7 and human lung cancer A549. Their SAR was studied and variously affected by the electronic factor of electron donating and withdrawing groups. Many of the tested compounds showed moderate to high anticancer activity.

Keywords: 1,3,4-Thiadiazole; 1,3-Thiazole; 1,3-Thiazolidin-4-one; Anticancer activity; Pyrazole.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Pyrazoles / chemistry*
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Pyrazoles
  • Thiadiazoles
  • Thiazoles
  • 1,3,4-thiadiazole
  • pyrazole