Development of novel antiatherogenic biaryls: design, synthesis, and reactivity.
On the basis of the 5,5'-bisvanillin scaffold, a series of compounds has been synthesized presenting symmetric or dissymmetric frames on each phenolic moiety. These frames are alpha,beta-unsaturated (fluoro)phosphonate and/or alpha,beta-unsaturated hydrazone(s) formed by coupling aldehydic with isoniazid or hydralazine. All compounds were tested for their ability to inhibit cell-mediated low-density lipoprotein oxidation. Oxidized low-density lipoprotein induced cytotoxicity was also evaluated along with the carbonyl scavenger properties of selected compounds. The most efficient agents were found to be those possessing at least one hydralazinone frame, with the most potent being the symmetrical compound: 4,4'-dihydroxy-3,3'-dimethoxy-5,5'-biphenyl-1,1'-(diphthalazin-1-yl)methylhydrazone hydrochloride.
Delomenède
Mélanie
M
Université Toulouse 3, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, LSPCMIB, UMR-CNRS 5068, Toulouse Cedex 9, France.
Bedos-Belval
Florence
F
Duran
Hubert
H
Vindis
Cécile
C
Baltas
Michel
M
Nègre-Salvayre
Anne
A
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050050:Protein Carbonylation; D013329:Structure-Activity Relationship
C530304:4,4'-dihydroxy-3,3'-dimethoxy-5,5'-biphenyl-1,1'-(diphthalazin-1-yl)methylhydrazone; D000975:Antioxidants; D006834:Hydrazines; D006835:Hydrazones; D008077:Lipoproteins, LDL; D063065:Organophosphonates; D010793:Phthalazines