Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit?
A series of combretastatins possessing both a trimethoxy unit and other substituents on ring A has been synthesised and tested for cytotoxicity and their ability to interact with the protein tubulin. All previous studies have indicated that the trimethoxy unit is essential for interaction with tubulin. The studies herein show that molecules possessing functionalities other than trimethoxy can also interact with tubulin. Importantly a trimethyl substituted agent 52a has shown reduced cytotoxicity, but increased potency in its ability to inhibit the assembly of tubulin.
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001632:Bibenzyls / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015394:Molecular Structure; D013267:Stilbenes / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects*; D014709:Vero Cells
D000970:Antineoplastic Agents; D001632:Bibenzyls; D013267:Stilbenes; D014404:Tubulin; C040105:combretastatin