Tubulin binding of two 1-deaza-7,8-dihydropteridines with different biological properties: enantiomers NSC 613862 (S)-(-) and NSC 613863 (R)-(+).

@article{Leynadier1993TubulinBO,
  title={Tubulin binding of two 1-deaza-7,8-dihydropteridines with different biological properties: enantiomers NSC 613862 (S)-(-) and NSC 613863 (R)-(+).},
  author={D. Leynadier and V. Peyrot and M. Sarrazin and C. Briand and J. Andreu and G. Rener and C. Temple},
  journal={Biochemistry},
  year={1993},
  volume={32 40},
  pages={
          10675-82
        }
}
Several fluorescence properties of two enantiomers, NSC 613862 (S)-(-) and NSC 613863 (R)-(+), have been compared. Even though the two isomers showed the same fluorescence behavior in solution in different solvents, drastic differences were observed after binding to purified calf brain tubulin. Binding measurements for the two compounds were performed both by fluorescence spectroscopy and by column gel permeation, a direct method of measurement. For both isomers, the binding was characterized… Expand
Molecular interaction of tubulin with 1-deaza-7,8-dihydropteridines: a comparative study of enantiomers NSC 613862 (S) and NSC 613863 (R) by Raman and Fourier transform infrared spectroscopy.
TLDR
Pre-resonance Raman spectroscopy has been applied to compare the vibrational modes of the R and S chiral isomers of 1-deaza-7,8-dihydropteridine when they are bound to tubulin, suggesting that R andS isomers differ in terms of their orientation in front of the binding locus of tubulin. Expand
Inhibition of Microtubules and Cell Cycle Arrest by a New 1-Deaza-7 , 8-dihydropteridine Antitumor Drug , CI 980 , and by Its Chiral Isomer , NSC 6138631
CI 980 (NSC 613862; [S-(-)]) and NSC 613863 [R-(+)] are the two chiral isomers of ethyl 5-amino 1,2-dihydro-2-methyl-3.phenylpyrido[3,4b]pyrazin-7-ylcarbamate (NSC 370147), which is a mitoticExpand
Conformational mimetics of the α-methyl chalcone TUB091 binding tubulin: Design, synthesis and antiproliferative activity.
TLDR
Based on the recently reported complex of combretastatin A4 with tubulin, a comparative analysis of the binding mode of CA4 and the α-methyl chalcone to tubulin has been performed and the 5-amino-6-methoxy derivative showed antiproliferative activity against tumor and endothelial cells. Expand
Targeting the colchicine site in tubulin through cyclohexanedione derivatives
Cyclohexanedione derivatives represent a new family of colchicine-site binders that were identified through a ligand-based virtual screening approach. Structural modifications have now been performedExpand
Antivascular and antitumor properties of the tubulin-binding chalcone TUB091
TLDR
The data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs) and provide evidence that the prodrug approach may be valuable for the development of anti-cancer drugs. Expand
Caulerpenyne binding to tubulin: structural modifications by a non conventional pharmacological agent.
TLDR
The most widely used molecules in cancer chemotherapy are Vinca-alkaloids and Taxoids, numerous chemists attempted the synthesis of analogs which bind to their well-known tubulin pharmacological site, but it is demonstrated that Cyn did not bind covalently to tubulin and evidenced two good candidate regions for Cyn binding, one on alpha-tubulin and the other on beta- Tubulin. Expand
High-affinity ligands of the colchicine domain in tubulin based on a structure-guided design
TLDR
These new compounds showed potent antiproliferative activity with IC50 values in the nM range, arrested cell cycle progression at the G2/M phase and induced apoptosis at sub μM concentrations and displayed high affinity for tubulin as substantiated by a Kb value of 2.87 × 108 M−1 which, to the best of the authors' knowledge, represents the highest binding constant measured to date for a colchicine-domain ligand. Expand
Theoretical studies of the ground state and of the spectroscopic properties of ethyl 5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate analogs
Abstract The interaction of antimitotic compounds with tubulin has been studied in detail in our laboratory; among them, the two chiral isomers of ethylExpand
Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.
TLDR
The approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties and one of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues. Expand
Diphenyl ether derivatives occupy the expanded binding site of cyclohexanedione compounds at the colchicine site in tubulin by movement of the αT5 loop.
TLDR
Based on a structure-guided design, new cyclohexanedione derivatives have been synthesized and tested for tubulin binding and in cellular assays and they halted the cell cycle progression at G2/M phase at concentrations as low as 0.08 μM. Expand
...
1
2
...

References

SHOWING 1-10 OF 34 REFERENCES
Mechanism of binding of the new antimitotic drug MDL 27048 to the colchicine site of tubulin: equilibrium studies.
TLDR
In contrast with close analogues of colchicine, MDL 27048 and podophyllotoxin neither affected the far-ultraviolet circular dichroism spectrum of tubulin, within experimental error, nor induced tubulin GTPase activity. Expand
Interaction of tubulin with bifunctional colchicine analogues: an equilibrium study.
TLDR
Excess analogue concentration under microtubule-promoting conditions induces an abnormal cooperative polymerization of tubulin, similar to that of the tubulin-colchicine complex. Expand
Interaction of tubulin and cellular microtubules with the new antitumor drug MDL 27048. A powerful and reversible microtubule inhibitor.
TLDR
This anti-tumor drug constitutes a new and potent microtubule inhibitor, characterized by its specificity and reversibility. Expand
Comparison of 1,2-dihydropyrido[3,4-b]pyrazines (1-deaza-7,8-dihydropteridines) with several other inhibitors of mitosis.
TLDR
Emphasis in further testing was placed upon NSC 370147, because it is easier to synthesize and is more stable than some of the other compounds of this type and because its greater solubility in water facilitates its formulation for therapeutic administration. Expand
Interactions of a new antimitotic agent, NSC-181928, with purified tubulin.
  • E. Hamel, C. Lin
  • Biology, Medicine
  • Biochemical and biophysical research communications
  • 1982
Abstract We have examined interactions of tubulin with ethyl 5-amino-1,2-dihydro-3-[( N -methylanilino)methyl]pyrido[3,4- b ]pyrazin-7-ylcarbamate (NSC-181928), a drug with structural similarity toExpand
Podophyllotoxin as a probe for the colchicine binding site of tubulin.
TLDR
It is concluded that both podophyllotoxin and colchicine each have at least two points of attachment to tubulin and that they share one of them, the binding region of the trimethoxyphenyl moiety. Expand
The effect of TN-16 on the alkylation of tubulin.
TLDR
It is 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. Expand
Mechanism of colchicine binding to tubulin. Tolerance of substituents in ring C' of biphenyl analogues.
TLDR
A concerted analysis of the binding thermodynamics of colchicine and its various analogues has shown full consistency with the previously proposed two-step binding pathway that involves two nonidentical binding moieties in the ligand. Expand
Conformational states of tubulin liganded to colchicine, tropolone methyl ether, and podophyllotoxin.
TLDR
The conformational effects of colchicine, podophyllotoxin, and tropolone methyl ether binding to tubulin have been studied and the tubulin-colchicines complex appears to be nonidentical with that of the unliganded protein. Expand
Differential binding of methyl benzimidazol-2-yl carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans
TLDR
Electrophoretic analysis of partially purified preparations of the binding protein of Aspergillus nidulans revealed the presence of proteins with similar mobilities as mammalian tubulin monomers, and it is concluded that the bindingprotein is identical with fungal tubulin. Expand
...
1
2
3
4
...