Article citationsMore>>

Gwaltney Ⅱ, S.L., Imade, H.M., Barr, K.J., Li, Q., Gehrke, L., Credo, R.B., Warner, R.B., Lee, J.Y., Kovar, P., Wang, J., Nukkala, M.A., Zielinski, N.A., Frost, D., Ng, S.C. and Sham, H.L. (2001) Novel Sulfonate Analogues of Combretastatin A-4: Potent Antimitotic Agents. Bioorganic & Medicinal Chemistry Letters, 11, 871-874.
http://dx.doi.org/10.1016/S0960-894X(01)00098-1

has been cited by the following article:

• TITLE: Novel Cytocidal Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl) Benzenesulfonates and Benzenesulfonamides with Affinity to the Colchicine-Binding Site: Is the Phenyl 2-Imidazolidinone Moiety a New Haptophore for the Design of New Antimitotics?

  AUTHORS: Sébastien Fortin, Lianhu Wei, Lakshmi P. Kotra, René C.-Gaudreault

  KEYWORDS: Docking, Colchicine-Binding Site Ligands, Antimicrotubule Agents, PIB-SO, PIB-SA

  JOURNAL NAME: Open Journal of Medicinal Chemistry, Vol.5 No.1, March 24, 2015

  ABSTRACT: Phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and phenyl 4-(2-oxoimidazolidin- 1-yl)benzenesulfonamides (PIB-SAs) are new, potent combretastatin A-4 (CA-4) analogs designed on the basis of their common phenyl 2-imidazolidone moiety. This phenyl 2-imidazolidone group is a bioisosteric equivalent of the trimethoxyphenyl group also found in colchicine, podophyllotoxin and several other ligands of the colchicine-binding site (C-BS). In this study, we investigate the interactions involved in the binding of PIB-SO and PIB-SA into the C-BS. We describe three distinct pockets (I, II, and III) as key structural elements involved in the interactions between the C-BS and PIB-SOs as well as PIB-SAs. We show that PIB-SOs and PIB-SAs adopt 4 and 3 distinct binding conformations, respectively, within the C-BS. The binding conformations I and IV are common to most PIB-SOs and PIB-SAs exhibiting high affinity for the C-BS and high cytocidal potency. In addition, binding conformation I is the main conformation adopted by PIB-SOs, PIB-SAs, T138067, ABT-751, colchicine and CA-4. We also observe that the sulfonate and the sulfonamide moieties of PIB-SOs and PIB-SAs are bioisosteric equivalents. Interestingly, we further find that a large portion of the phenyl 2-imidazolidinone moiety in these analogs does not bind to pocket I unlike the trimethoxyphenyl moiety found in several antimicrotubule agents such as colchicine, CA-4 and podophyllotoxin, suggesting that the phenyl 2-imidazolidinone group may represent a new haptophoric moiety useful for the design of new C-BS inhibitors mimicking the tropolone and the methoxylated phenolic moieties of colchicine and CA-4, respectively.