2. Academic Validation
  3. Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities

Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities

  • Bioorg Med Chem Lett. 2016 Jul 1;26(13):3167-3171. doi: 10.1016/j.bmcl.2016.04.080.
Mukund P Tantak 1,  Vishakha Gupta 1,  Kumar Nikhil 2,  V Arun 1,  Rajnish Prakash Singh 3,  Prabhat Nath Jha 3,  Kavita Shah 4,  Dalip Kumar 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
  • 2 Department of Chemistry, Purdue University Center for Cancer Research, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
  • 3 Department of Biological Sciences, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
  • 4 Department of Chemistry, Purdue University Center for Cancer Research, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA. Electronic address: shah23@purdue.edu.
  • 5 Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.
PMID: 27173802 DOI: 10.1016/j.bmcl.2016.04.080
Abstract

A series of bis(indolyl)glyoxylamides 10a-n has been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole 9 with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides 10a-n in 82-93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their Antibacterial activity against Gram-positive and Gram-negative Bacterial strains. Compounds 10d, 10g and 10i were found to display potent Antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human Cancer cell lines. Of the screened analogues, compound 10f (IC50=22.34μM; HeLa, 24.05μM; PC-3, 21.13μM; MDA-MB-231 and 29.94μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either 10a or 10f resulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce Apoptosis in PC-3 cells. Most importantly, compounds 10d, 10g and 10i were completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells.

Keywords

Antibacterial; Apoptosis; Bisindoles; Cancer; Cytotoxicity; Glyoxylamides.

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