AI Article Synopsis
- Researchers studied alkenyldiarylmethane (ADAM) compounds, finding some that were cytotoxic at low micromolar levels and linked to a tubulin polymerization inhibitor, CC-5079.
- A series of 14 ADAM compounds were tested for their ability to inhibit tubulin polymerization, revealing that most were ineffective, but two showed significant inhibitory activity.
- The two most cytotoxic ADAM compounds were found to inhibit tubulin assembly and demonstrated strong anticancer activity in tests against 60 human cancer cell lines, yielding submicromolar cytotoxicity levels.
Article Abstract
During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC(50) values of 3.7+/-0.3 and 2.8+/-0.2 microM, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31+/-0.08 and 0.47+/-0.09 microM, respectively.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2255563 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2007.11.114 | DOI Listing |
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