Binding of cosalane - A novel highly lipophilic anti-HIV agent - To albumin and glycoprotein

Kameswara R. Kuchimanchi, Mahmoud S. Ahmed, Thomas P. Johnston, Ashim K. Mitra

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Cosalane is a potent inhibitor of HIV replication with multiple sites of action. The purposes of this study were to (a) determine the extent and nature of cosalane binding to mucin, α1-acid glycoprotein (AAG), plasma, and human (HSA) and bovine serum (BSA) albumin, and (b) determine the primary site(s) of cosalane binding to HSA. Plasma protein binding of cosalane was studied by a gel filtration technique. Cosalane binding to HSA was also determined in the presence of salicylic acid. Competitive inhibition studies were conducted using warfarin, digitoxin, and diazepam to determine the primary HSA binding site(s) of cosalane. The drug was bound extensively to HSA and BSA and required 500-550 moles to saturate 1 mole of protein. Stoichiometries of cosalane binding to α1-acid glycoprotein (AAG) and mucin were between 30 and 50 mol/mol of either glycoprotein. The binding isotherm deviated from a rectangular hyperbola, suggesting self-association of the ligand. Salicylic acid decreased cosalane binding to HSA by one order of magnitude. Inhibition studies of cosalane to HSA revealed that the compound binds primarily to warfarin site with a Ki of 1.24 ± 0.24 nM. In summary, cosalane binds extensively to serum albumins and to a lesser extent to both AAG and mucin.

Original languageEnglish (US)
Pages (from-to)659-666
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number5
StatePublished - 2001
Externally publishedYes


  • Competitive inhibition
  • Cosalane
  • Gel filtration
  • Protein binding
  • Self-association

ASJC Scopus subject areas

  • Pharmaceutical Science


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