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Design and synthesis of novel N,N′-glycoside derivatives of 3,3′-diindolylmethanes as potential antiproliferative agents

MedChemComm, ISSN: 2040-2503, Vol: 3, Issue: 9, Page: 1082-1091
2012
  • 33
    Citations
  • 0
    Usage
  • 23
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    33
    • Citation Indexes
      33
  • Captures
    23

Article Description

A library of 34 compounds containing the DIM core have been synthesized and tested for their anticancer efficacy by measuring their cytotoxicity to cancer cell lines A549, HeLa and MCF-7. Some of the selected derivatives were N-glycosylated to increase their efficacy. Compound 7d, an N-glycosylated DIM derivative, was found to be effective at 1.3, 0.3 and 0.9 μmol concentrations against A549, HeLa and MCF-7, respectively. Immunochemistry studies revealed that it could induce apoptosis by upregulating a pro-apoptotic protein Par-4 and concomitantly diminishing the expression of pro-survival proteins Bcl-2 and GRP78. Flow cytometry studies showed that the compound arrested cells in the G1 phase of the cell cycle and significantly abrogated the motility of HeLa cells. Computer docking simulations of 7d with GRP78 suggested its involvement in two H-bonds with Asp78, two H-bonds with Arg290, one with Arg367, and one water mediated H-bond interaction. The interaction patterns also demonstrated that the presence of bromide in the vicinity (within 3.5 Å) of Lys294 generates the possibility of a halogen bond, which may also contribute in providing some extra stability to the complex. Hence, compounds of this class will be useful for the design of new anticancer agents. © 2012 The Royal Society of Chemistry.

Bibliographic Details

Deepak K. Sharma; Mallikharjuna R. Lambu; Altaf Hussain; Syed K. Yousuf; Anil K. Tripathi; Baldev Singh; Debaraj Mukherjee; Bilal Rah; Gayatri Jamwal; Zabeer Ahmed; Anindya Goswami; Nayan Chanauria; Amit Nargotra

Royal Society of Chemistry (RSC)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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