Synthesis, antioxidant and anti-inflammatory activity of novel substituted ethylenediamines and ethanolamines. A preliminary quantitative structure-activity relationship study.
Six substituted oxo- or hydroxy-aminoethanols and ethylenediamines were synthesized and tested as anti-inflammatory agents. 1-Substituted 4-(2-aminoethylamino)-1-butanones and 1-substituted 4-(2-hydroxy-ethylamino)-1-butanones were prepared by reacting the appropriate 4-chloro-1-butanone with the corresponding aminoalcohol or ethylenediamine. 1-Substituted 4-(2-aminoethylamino)-1-butanols were prepared by the reduction of the ketones with NaBH4 or NaBH3CN. The RM values of the synthesized compounds were determined as an expression of their lipophilicity. The effect of these compounds on in vitro non-enzymatic lipid peroxidation, their hydroxyl radical scavenging activity and their ability to interact with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH) were studied. The effect of the synthesized compounds on inflammation, using the carrageenan induced rat paw edema model was studied. Both anti-inflammatory and antioxidant activities depended on some structural characteristics of the synthesized compounds. It was also attempted to correlate the above mentioned activities with some physicochemical parameters using a quantitative structure-activity relationship approach. The primary amino group appeared to be of importance for antioxidant activity in this series of compounds.
Andreadou
I
I
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece.
Rekka
E A
EA
Demopoulos
V J
VJ
Bijloo
G J
GJ
Kourounakis
P N
PN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan; D002855:Chromatography, Thin Layer; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004983:Ethanolamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004983:Ethanolamines; D005029:Ethylenediamines; D005609:Free Radicals; D002351:Carrageenan; D004121:Dimethyl Sulfoxide