Improved anticancer and antiparasitic activity of new lawsone Mannich bases

  • Eur J Med Chem. 2017 Jan 27:126:421-431. doi: 10.1016/j.ejmech.2016.11.043.
Katharina Mahal  1 ,  Aamir Ahmad  2 ,  Florian Schmitt  1 ,  Julia Lockhauserbäumer  3 ,  Kathrin Starz  3 ,  Rohan Pradhan  4 ,  Subhash Padhye  4 ,  Fazlul H Sarkar  2 ,  Waleed S Koko  5 ,  Rainer Schobert  1 ,  Klaus Ersfeld  3 ,  Bernhard Biersack  6
Affiliations
  • 1. Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
  • 2. Karmanos Cancer Institute, Dept. of Pathology, Wayne State University, Detroit 48201, USA.
  • 3. Laboratory of Molecular Parasitology, Department of Genetics, University of Bayreuth, 95440 Bayreuth, Germany.
  • 4. Department of Chemistry, Abeda Inamdar Senior College, Pune 411001, India.
  • 5. Department of Microbiology and Parasitology, Medicinal and Aromatic Plants Research Institute, National Centre for Research, Khartoum, Sudan; College of Science and Arts (Ar Rass), Qassim University, Buraidah, Saudi Arabia.
  • 6. Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany. Electronic address: [email protected].
PMID: 27912173 DOI: 10.1016/j.ejmech.2016.11.043
Abstract

Substituted lawsone Mannich Bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human Cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule Cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica Parasite samples exceeding the activity of metronidazole.

Keywords
Anticancer drugs; Antiparasitic drugs; Lawsone; Mannich base.