Synthesis of 2-, 4- and 5-benzoylpyrrole-3-acetic acids and study of their in vitro effects on active oxygen species.
The isomeric benzoylpyrrole-3-acetic acids 2a-4a were synthesized on the basis of the known biological interest of analogous pyrrole-1- and pyrrole-2-acetic acids. The electrophilic benzoylation of ethyl pyrrole-2-acetate was found to give mixtures of the three substituted on the carbon atoms of the pyrrole ring isomers 2-4 in ratios which varied with the employed conditions. Experimental procedures were developed for the preferential formation of each one of the isomers in synthetically useful amounts. The involvement of the synthesized compounds in active oxygen intermediates was tested in vitro by examining their effect on lipid peroxidation using heat inactivated rat hepatic microsomes, and as hydroxyl radical scavengers, by determining the inhibition of formaldehyde production from the oxidation of DMSO. For comparison, some ESR spectra were recorded. It was found that 3 moderately inhibited lipid peroxidation, while all derivatives tested were potent hydroxyl radical scavengers. It is proposed that the reported compounds could find useful applications as protective agents against oxygen toxicity.
Demopoulos
V J
VJ
Department of Pharmacy, University of Thessaloniki, Greece.
Rekka
E
E
Retsas
S
S
D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004121:Dimethyl Sulfoxide; D004578:Electron Spin Resonance Spectroscopy; D005557:Formaldehyde / Q000032:analysis; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology
D000085:Acetates; D005609:Free Radicals; D011758:Pyrroles; D005557:Formaldehyde; D010100:Oxygen; D004121:Dimethyl Sulfoxide