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Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol
Universidade Federal do Amazonas, Avenida General Rodrigo Otávio Jordão Ramos, 3000, 69077-000 Campus Universitário, Manaus, Amazonas, Brazil
Instituto Nacional de Pesquisas da Amazônia, Avenida André Araújo, 2936, 69067-375 Aleixo, Manaus, Amazonas, Brazil
Embrapa Amazônia Ocidental, Rodovia AM-010, Km 29, Zona Rural, 69010-970 Caixa Postal 319 Manaus, Amazonas, Brazil
* Author to whom correspondence should be addressed.
Received: 26 October 2012; in revised form: 16 November 2012 / Accepted: 20 November 2012 / Published: 24 December 2012
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.
Keywords: ABTS; antioxidants; bioactivity; cytotoxicity; DPPH; natural product derivatives; 4-NC; Piper peltatum; radical scavenger activity; stability
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Lima, E.S.; Pinto, A.C.S.; Nogueira, K.L.; Silva, L.F.R.; Almeida, P.D.O.; Vasconcellos, M.C.; Chaves, F.C.M.; Tadei, W.P.; Pohlit, A.M. Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol. Molecules 2013, 18, 178-189.
Lima ES, Pinto ACS, Nogueira KL, Silva LFR, Almeida PDO, Vasconcellos MC, Chaves FCM, Tadei WP, Pohlit AM. Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol. Molecules. 2013; 18(1):178-189.
Lima, Emerson S.; Pinto, Ana C.S.; Nogueira, Karla L.; Silva, Luiz F.R.; Almeida, Patricia D.O.; Vasconcellos, Marne C.; Chaves, Francisco C.M.; Tadei, Wanderli P.; Pohlit, Adrian M. 2013. "Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol." Molecules 18, no. 1: 178-189.