Cathepsin B inhibitory activities of phthalates isolated from a marine Pseudomonas strain

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2083-8. doi: 10.1016/j.bmcl.2008.01.097. Epub 2008 Jan 30.

Abstract

Two cathepsin B inhibitors were isolated from the culture supernatant of a marine Pseudomonas sp. PB01 (GenBank Accession No. EU126129). Their structures were elucidated by spectroscopic analyses as dibutyl phthalate and di-(2-ethylhexyl) phthalate. Both dibutyl phthalate and di-(2-ethylhexyl) phthalate showed dose-dependent cathepsin B inhibitions with IC(50) of 0.42 and 0.38 mM, respectively. It is also observed from kinetic analyses that dibutyl phthalate and di-(2-ethylhexyl) phthalate acted as noncompetitive inhibitors with K(i) values of 0.64 and 0.42 mM, respectively. Furthermore, both of them caused inactivation of the pericellular cathepsin B of murine melanoma cell with no acute cytotoxicity. The IC(50) values were found to be 0.23 mM for dibutyl phthalate and 0.14 mM for di-(2-ethylhexyl) phthalate, respectively, and were 50% compared to that of purified cathepsin B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin B / metabolism
  • Cells, Cultured
  • Dibutyl Phthalate / pharmacology*
  • Diethylhexyl Phthalate / pharmacology*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Marine Biology
  • Melanoma, Experimental / drug therapy*
  • Mice
  • Molecular Structure
  • Protease Inhibitors / pharmacology*
  • Pseudomonas / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Protease Inhibitors
  • RNA, Messenger
  • Dibutyl Phthalate
  • Diethylhexyl Phthalate
  • Cathepsin B