Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors.
Gallic acid, one of the most abundant plant phenolic acids, has been modified to cathepsin D protease inhibitors. The strategy of modification was proposed basing on some previously reported structure and activity relationship (SAR) studies. The synthesized naphthophenone fatty acid amide derivatives have been evaluated for in vitro cathepsin D inhibition activity. Two of them have shown significant inhibition activity with IC(50) values of 0.06 and 0.14 microM, respectively, as compared against pepstatin (0.0023 microM), the most potent inhibitor known so far. The study revealed that such attempts on gallic acid based pharmacophores might result in potent inhibitors of cathepsin D.
Srivastava
Vandana
V
Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Lucknow, India.
Saxena
Hari Om
HO
Shanker
Karuna
K
Kumar
J K
JK
Luqman
Suaib
S
Gupta
M M
MM
Khanuja
S P S
SP
Negi
Arvind S
AS
D000577:Amides / Q000737:chemistry*; D002402:Cathepsin D / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry*; D005707:Gallic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D010436:Pepstatins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D005227:Fatty Acids; D007659:Ketones; D009281:Naphthalenes; D010436:Pepstatins; D005707:Gallic Acid; D002402:Cathepsin D; C031375:pepstatin