Novel trisubstituted harmine derivatives with original in vitro anticancer activity.
Summary of "Novel trisubstituted harmine derivatives with original in vitro anticancer activity."
To overcome the intrinsic resistance of cancer cells to apoptotic stimuli, we designed and synthesized approximately 50 novel β-carbolines structurally related to harmine. Harmine is known for its anticancer properties and is a DYRK1A inhibitor. Of the synthesized compounds, the most active in terms of growth inhibition of five cancer cell lines are cytostatic and approximately 100 times more potent than harmine but demonstrated no DYRK1A inhibitory activity. These novel β-carbolines display similar growth inhibitory activity in both cancer cells that are sensitive and resistant to apoptotic stimuli. Using ChemGPS-NP, we found that the more active β-carbolines are all more lipophilic and larger than the less active compounds. Lastly, based on NCI Human Tumor Cell Line Anti-Cancer Drug Screen and the NCI COMPARE algorithm, it appears that some of these compounds, including 5a and 5k, seem to act as protein synthesis inhibitors.
Affiliation
Journal Details
This article was published in the following journal.
Name: Journal of medicinal chemistry
ISSN: 1520-4804
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22770529
- DOI: http://dx.doi.org/10.1021/jm300542e
Medical and Biotech [MESH] Definitions
Drug Screening Assays, Antitumor
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Nucleic Acid Amplification Techniques
Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template.
Lignans
A class of dibenzylbutane derivatives which occurs in higher plants and in fluids (bile, serum, urine, etc.) in man and other animals. These compounds, which have a potential anti-cancer role, can be synthesized in vitro by human fecal flora. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Rubber
A high-molecular-weight polymeric elastomer derived from the milk juice (LATEX) of HEVEA brasiliensis and other trees and plants. It is a substance that can be stretched at room temperature to at least twice its original length and after releasing the stress, retract rapidly, and recover its original dimensions fully.
Banisteriopsis
A plant genus of the family MALPIGHIACEAE which includes an Amazonian psychoactive plant that contains the beta-carboline harmine and N,N-dimethyltryptamine.
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