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Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile.

Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4... The novel agents amphethinile and combretastatin A4 are shown to be very similar to colchicine in their interactions with purified tubulin. All three agents can inhibit tubulin assembly at similar treatment levels and have comparable affinity constants for tubulin. Amphethinile and combretastatin A4 are capable of displacing colchicine but not vinblastine from tubulin. A comparison of the structures of these agents shows that whereas colchicine and combretastatin A4 contain a trimethoxybenzene group (a moiety also found in other colchicine-like agents such as podophyllotoxins and steganacin) no obvious similarity is seen for amphethinile. The three-dimensional structures of these agents, determined from either crystallographic data or by energy minimization procedures, show, however, that all three agents consist of two planar, or almost planar, ring systems which are tilted with respect to each other. Using computer graphic techniques it can be shown that their ring systems are superimposable and that the planar sections of each molecule are at an angle of 50-60 degrees to each other. It is proposed that the angular bicyclic structure of these agents is one determining factor for their efficient binding to tubulin. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Anti-cancer drug design Pubmed

Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile.

Anti-cancer drug design , Volume 3 (4): 6 – May 18, 1989

Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile.


Abstract

The novel agents amphethinile and combretastatin A4 are shown to be very similar to colchicine in their interactions with purified tubulin. All three agents can inhibit tubulin assembly at similar treatment levels and have comparable affinity constants for tubulin. Amphethinile and combretastatin A4 are capable of displacing colchicine but not vinblastine from tubulin. A comparison of the structures of these agents shows that whereas colchicine and combretastatin A4 contain a trimethoxybenzene group (a moiety also found in other colchicine-like agents such as podophyllotoxins and steganacin) no obvious similarity is seen for amphethinile. The three-dimensional structures of these agents, determined from either crystallographic data or by energy minimization procedures, show, however, that all three agents consist of two planar, or almost planar, ring systems which are tilted with respect to each other. Using computer graphic techniques it can be shown that their ring systems are superimposable and that the planar sections of each molecule are at an angle of 50-60 degrees to each other. It is proposed that the angular bicyclic structure of these agents is one determining factor for their efficient binding to tubulin.

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ISSN
0266-9536
pmid
2930627

Abstract

The novel agents amphethinile and combretastatin A4 are shown to be very similar to colchicine in their interactions with purified tubulin. All three agents can inhibit tubulin assembly at similar treatment levels and have comparable affinity constants for tubulin. Amphethinile and combretastatin A4 are capable of displacing colchicine but not vinblastine from tubulin. A comparison of the structures of these agents shows that whereas colchicine and combretastatin A4 contain a trimethoxybenzene group (a moiety also found in other colchicine-like agents such as podophyllotoxins and steganacin) no obvious similarity is seen for amphethinile. The three-dimensional structures of these agents, determined from either crystallographic data or by energy minimization procedures, show, however, that all three agents consist of two planar, or almost planar, ring systems which are tilted with respect to each other. Using computer graphic techniques it can be shown that their ring systems are superimposable and that the planar sections of each molecule are at an angle of 50-60 degrees to each other. It is proposed that the angular bicyclic structure of these agents is one determining factor for their efficient binding to tubulin.

Journal

Anti-cancer drug designPubmed

Published: May 18, 1989

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