title: Synthesis and classical pathway Complement inhibitory activity of C7-functionalized filifolinol derivatives, inspired in K-76 COOH.
abstract: A series of carboxylic acids carrying various functionalization on C-7 of their common 3H-spiro[benzofuran-2,1'-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural Complement inhibitor K-76 COOH. In order to probe the relevance of the C-7 functionalization on their bioactivity, the ability of the analogs to inhibit Complement activation through the classical pathway was determined. The observed results suggest that functionalization of C-7 can modulate the inhibitory activity of the tested compounds. The 7-trifluoromethyl derivative was the compound with the lowest IC(50) value among the tested analogs (IC(50) = 100 μM), being more potent than K-76 COOH (IC(50) = 570 μM).
authors: Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, S2002LRK Rosario, Argentina. larghi@iquir-conicet.gov.ar
authors: Enrique L
authors: EL
authors: Larghi
authors: María A
authors: MA
authors: Operto
authors: Rene
authors: R
authors: Torres
authors: Teodoro S
authors: TS
authors: Kaufman
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D012717:Sesquiterpenes / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D012717:Sesquiterpenes; D013141:Spiro Compounds; C560648:filifolinol acetate; C038797:K 76 carboxylic acid; D003165:Complement System Proteins