AI Article Synopsis
- Despite the rise of new therapeutic targets for cancer treatment, antitubulin drugs like TN-16 continue to play a vital role in cancer therapies for both adults and children.
- Researchers developed a new, efficient method to produce TN-16 and its aza-analogs, creating a library of 62 compounds, with three showing strong potency against cancer cells.
- The active compounds demonstrated their ability to induce cell cycle arrest and disrupt microtubules, leading to increased α-tubulin acetylation, although their impact on cellular tubulin polymerization was less pronounced.
Article Abstract
Despite novel biological targets emerging at an impressive rate for anticancer therapy, antitubulin drugs remain the backbone of numerous oncological protocols and their efficacy has been demonstrated in a wide variety of adult and pediatric cancers. In the present contribution, we set to develop analogs of a potent but neglected antitubulin agent, TN-16, originally discovered via modification of tenuazonic acid (3-acetyl-5-sec-butyltetramic acid). To this extent, we developed a novel multicomponent reaction to prepare TN-16, and then we applied the same reaction for the synthesis of aza-analogs. In brief, we prepared a library of 62 novel compounds, and three of these retained nanomolar potencies. TN-16 and the active analogs are cytotoxic on cancer cell lines and, as expected from antitubulin agents, induce G/M cell cycle arrest. These agents lead to a disruption of the microtubules and an increase in α-tubulin acetylation and affect in vitro polymerization, although they have a lesser effect in cellular tubulin polymerization assays.
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| http://dx.doi.org/10.1016/j.ejmech.2022.114895 | DOI Listing |
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