Design, Synthesis and Anticancer Screening of Novel Benzothiazole-Piperazine-1,2,3-Triazole Hybrids

Molecules. 2018 Oct 27;23(11):2788. doi: 10.3390/molecules23112788.

Abstract

A library of novel regioselective 1,4-di and 1,4,5-trisubstituted-1,2,3-triazole based benzothiazole-piperazine conjugates were designed and synthesized using the click synthesis approach in the presence and absence of the Cu(I) catalyst. Some of these 1,2,3-triazole hybrids possess in their structures different heterocyclic scaffold including 1,2,4-triazole, benzothiazole, isatin and/or benzimidazole. The newly designed 1,2,3-triazole hybrids were assessed for their antiproliferative inhibition potency against four selected human cancer cell lines (MCF7, T47D, HCT116 and Caco2). The majority of the synthesized compounds demonstrated moderate to potent activity against all the cancer cell lines examined. Further, we have established a structure activity relationship with respect to the in silico analysis of ADME (adsorption, distribution, metabolism and excretion) analysis and found good agreement with in vitro activity.

Keywords: 1,2,3-triazole; Benzothiazole; anticancer activity; piperazine.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzothiazoles / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic*
  • Drug Design*
  • Drug Screening Assays, Antitumor* / methods
  • Humans
  • Magnetic Resonance Spectroscopy
  • Piperazine / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship
  • Triazoles / chemistry*

Substances

  • Antineoplastic Agents
  • Benzothiazoles
  • Triazoles
  • Piperazine