Novel 1,4 substituted piperidine derivatives. Synthesis and correlation of antioxidant activity with structure and lipophilicity.
A series of novel piperidine derivatives was prepared and their lipophilicity was determined (as RM values). These compounds as well as two intermediate alpha-keto-esters were tested for antioxidant activity. It was found that the cysteamine derivatives were efficient antioxidants, i.e. they could inhibit lipid peroxidation, act as hydroxyl radical scavengers and interact with 2,2-diphenyl-1-picrylhydrazyl radicals. This interaction could be attributed to the free SH group and this activity seemed to be favoured by increased lipophilicity. Replacement of SH by NH2 or OH resulted in a decreased antioxidant activity of the compounds. However, the described activities seem not to be connected with any O2-.scavenging ability, at least under the experimental conditions applied. Furthermore, cysteamine derivatives seem to induce O2-.generation, a phenomenon often observed with thiol compounds. The antioxidant activity of the intermediate alpha-keto-esters varied and is probably mediated by different mechanisms.
Alexidis
A N
AN
Department of Pharmaceutical Chemistry, Aristotelian University of Thessaloniki, Greece.
Rekka
E A
EA
Demopoulos
V J
VJ
Kourounakis
P N
PN
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003543:Cysteamine / Q000737:chemistry; D004952:Esters; D005260:Female; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D004952:Esters; D016166:Free Radical Scavengers; D010880:Piperidines; D017382:Reactive Oxygen Species; D013481:Superoxides; D017665:Hydroxyl Radical; D003543:Cysteamine