Synthesis and in vitro evaluation of novel tetrazole embedded 1,3,5-trisubstituted pyrazoline derivatives as Entamoeba histolytica growth inhibitors

Eur J Med Chem. 2012 Aug:54:845-54. doi: 10.1016/j.ejmech.2012.03.049. Epub 2012 Apr 3.

Abstract

A series of pyrazoline derivatives (1a-15a) was synthesized by cyclization of chalcones (1-15) with 2-[5-(4-methoxyphenyl)-1H-tetrazol-1-yl]acetohydrazide under basic conditions and were screened in vitro, to find out effect on the growth of HM1: IMSS strain of Entamoeba histolytica. The compounds 3a, 4a, 11a, 13a and 14a showed encouraging results with IC(50) value in the range of 0.86-1.28 μM. However compound 13a showed most promising results with IC(50) = 0.86 μM which is half of the metronidazole, the standard drug used for protozoal infection. Cell viability test in human hepatocellular carcinoma cell line (HepG2) revealed non-toxic nature of new synthesized compounds. Safety index calculations prevailed compound 13a as highly antiamoebic and least cytotoxic (S.I. = >116.28), almost twice than metronidazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / toxicity
  • Cell Survival / drug effects
  • Chemistry Techniques, Synthetic
  • Entamoeba histolytica / drug effects*
  • Entamoeba histolytica / growth & development*
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyrazoles / toxicity
  • Tetrazoles / chemistry*

Substances

  • Antiprotozoal Agents
  • Pyrazoles
  • Tetrazoles