Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin

Biochim Biophys Acta. 1978 Dec 18;544(3):605-14. doi: 10.1016/0304-4165(78)90334-3.

Abstract

The binding and inhibitory properties of 11 benzimidazoles for bovine brain tubulin were investigated. The effects of the benzimidazoles on the initial rates of microtubule polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (I50) for nocodazole, oxibendazole, parbendazole, mebendazole and fenbendazole ranged from 1.97 . 10(-6) to 6.32 . 10(-6) M. Benomyl, cambendazole and carbendazim had I50 values from 5.83 . 10(-5) to 9.01 .10(-5) M. Thiabendazole had an I50 value of 5.49 . 10(-4) M. Inhibitor constants (Ki) were determined by the colchicine binding assay. Oxibendazole, fenbendazole, and cambendazole had Ki values of 3.20 . 10(-5), 1.73 . 10(-5) and 1.10 . 10(-4) M, respectively. Oxibendazole and fenbendazole were competitive inhibitors of colchicine. In contrast, cambendazole was a noncompetitive inhibitor of colchicine. The ability of these benzimidazoles to inhibit microtubule polymerization and the mode of action for the anthelmintic benzimidazoles is discussed.

MeSH terms

  • Animals
  • Anthelmintics / pharmacology*
  • Benzimidazoles / pharmacology
  • Brain / metabolism
  • Cattle
  • Cell-Free System
  • Colchicine / pharmacology
  • Dose-Response Relationship, Drug
  • Glycoproteins / metabolism*
  • Kinetics
  • Protein Binding / drug effects
  • Structure-Activity Relationship
  • Tubulin / metabolism*

Substances

  • Anthelmintics
  • Benzimidazoles
  • Glycoproteins
  • Tubulin
  • Colchicine