Glycosyl and polyalcoholic prodrugs of lonidamine

Bioorg Med Chem Lett. 2008 Apr 1;18(7):2445-50. doi: 10.1016/j.bmcl.2008.02.046. Epub 2008 Mar 5.

Abstract

Polyhydric alcohol derivatives of the anticancer agent lonidamine (LND) have been synthesized. The increased water solubility showed by prodrugs 4, 7, and 25 together with their logP values (2.19, 2.55, and 2.54, respectively) and chemical stability might be beneficial for prodrugs absorption after oral administration. Moreover, the new prodrugs undergo enzymatic hydrolysis in plasma and release LND demonstrating that they are promising candidates for in vivo investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Oral
  • Alcohols / chemistry*
  • Animals
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacokinetics*
  • Cell Line, Tumor
  • Glycosides / chemistry*
  • Humans
  • Hydrolysis
  • Indazoles / blood
  • Indazoles / chemical synthesis
  • Indazoles / pharmacokinetics*
  • Models, Chemical
  • Prodrugs / chemical synthesis
  • Prodrugs / metabolism*
  • Rats
  • Solubility
  • Structure-Activity Relationship
  • Water / chemistry

Substances

  • Alcohols
  • Antineoplastic Agents
  • Glycosides
  • Indazoles
  • Prodrugs
  • Water
  • lonidamine