title: Stability and antioxidant activity of semi-synthetic derivatives of 4-nerolidylcatechol.
abstract: 4-nerolidylcatechol (4-NC) is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl) on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast), however 4-NC was more cytotoxic (IC₅₀ = 31.4 µM) and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at -20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at -20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds.
authors.affiliation: Universidade Federal do Amazonas, Avenida General Rodrigo Otávio Jordão Ramos 3000, 69077-000 Campus Universitário, Manaus, Amazonas, Brazil.
authors.forename: Emerson
authors.initials: E
authors.lastname: Silva Lima
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Silva Pinto
authors.forename: Karla Lagos
authors.initials: KL
authors.lastname: Nogueira
authors.forename: Luiz Francisco
authors.initials: LF
authors.lastname: Rocha e Silva
authors.forename: Patricia Danielle
authors.initials: PD
authors.lastname: Oliveira de Almeida
authors.forename: Marne
authors.initials: M
authors.lastname: Carvalho de Vasconcellos
authors.forename: Francisco Celio Maia
authors.initials: FC
authors.lastname: Chaves
authors.forename: Wanderli Pedro
authors.initials: WP
authors.lastname: Tadei
authors.forename: Adrian Martin
authors.initials: AM
authors.lastname: Pohlit
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000737:chemistry / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000737:chemistry / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D017711:Nonlinear Dynamics; D031701:Piper / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development
chemical_list: C110583:4-nerolidylcatechol; D000962:Antimalarials; D000975:Antioxidants; D002396:Catechols; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole