Cathepsin B inhibitory activities of phthalates isolated from a marine Pseudomonas strain.
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.
Hoang
Van L T
VL
Department of Chemistry, Pukyong National University, 599-1 Daeyon 3-dong, Nam-gu, Busan 608-737, Republic of Korea.
Li
Yong
Y
Kim
Se-Kwon
SK
D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D003993:Dibutyl Phthalate / Q000494:pharmacology*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008386:Marine Biology; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000494:pharmacology*; D011549:Pseudomonas / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D011480:Protease Inhibitors; D012333:RNA, Messenger; D003993:Dibutyl Phthalate; D004051:Diethylhexyl Phthalate; D002401:Cathepsin B