The effect of TN-16 on the alkylation of tubulin.
The synthetic anti-tumor drug 3-(1-anilinoethylidene)-5-benzylpyrrolidine-2,4-dione (TN-16) is known to block microtubule assembly and colchicine binding to tubulin, although its structure does not resemble those of either colchicine, podophyllotoxin, or nocodazole (Arai, FEBS Lett. 155:273-276 (1983]. We have found that TN-16 affects the intra-chain cross-linking of beta-tubulin by N,N'-ethylene-bis(iodoacetamide) in a manner identical to that of colchicine, podophyllotoxin, and nocodazole, but different from that of vinblastine or maytansine. TN-16 also inhibits alkylation of tubulin by iodo[14C]acetamide, as do colchicine and its congeners. TN-16 appears to bind to tubulin at the colchicine binding site and one of its phenyl groups is likely to bind at the site on tubulin where colchicine's A ring binds.
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003078:Colchicine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000378:metabolism; D007460:Iodoacetamide / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*
D000970:Antineoplastic Agents; D005029:Ethylenediamines; D011760:Pyrrolidinones; D014404:Tubulin; C038092:TN 16; C032156:N,N'-ethylenebis(iodoacetamide); D003078:Colchicine; D007460:Iodoacetamide