Interaction of novel thiocolchicine analogs with the tubulin isoforms frombovine brain

The antimitotic alkaloid colchicine binds to tubulin and inhibits microtubu le assembly. Recently a new series of colchicine derivatives has been synth esized in which the seven-membered B-ring was Shortened to a six-membered r ing. In an effort to study the role of the B-ring substituents in this new series, we have studied the interaction of two compounds of this series, TH C 5 and THC 18, with tubulin isoforms from bovine brain. We find that THC 1 8, which has a side chain with a pi-bonded SP2 conformation, binds differen tly to the tubulin isoforms, while THC 5 with a slightly different side cha in does not. The results indicate that the conformation of the B-ring domai n plays a major role in the differential interaction of a colchicine deriva tive with different tubulin isoforms. The results will be very important in designing potent antitumor derivatives of colchicine. (C) 1999 Academic Pr ess.