Antihypertensive activity of chitin derivatives.
To develop angiotensin I converting enzyme (ACE) inhibitory chitin derivatives based on the properties of ACE inhibitors, chitins with different degree of deacetylation were chemically modified by grafting 2-chloroethylamino hydrochloride onto chitin at the C-6 position. Three kinds of chitin derivatives were prepared and designated as aminoethyl-chitin (AEC) with 10% degree of deacetylation, aminoethyl-chitin with 50% degree of deacetylation (AEC50), and aminoethyl-chitin with 90% degree of deacetylation (AEC90). IC50 values of three chitin derivatives on ACE were 0.064 microM (AEC), 0.038 microM (AEC50), and 0.103 microM (AEC90). The results of Dixon plots revealed that AEC50 was a competitive inhibitor, and the inhibition constant (Ki) value was 0.021 microM. In addition, the antihypertensive effect of AEC50 on spontaneously hypertensive rats (SHR) was evaluated, and the result showed that it effectively decreased systolic blood pressure (SBP) in a dose-dependent manner.
Je
Jae-Young
JY
Department of Chemistry, Pukyong National University, Busan 608-737, Korea.
Park
Pyo-Jam
PJ
Kim
Bokyung
B
Kim
Se-Kwon
SK
D000107:Acetylation; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002686:Chitin