Planta Med 2014; 80 - P1L67
DOI: 10.1055/s-0034-1394724

Cytotoxic potential of new phenylpropanoid derivatives isolated from Nectandra leucantha Nees & Mart (Lauraceae)

SS Grecco 1, EGA Martins 2, CR Figueiredo 3, N Girola 3, AL Matsuo 3, P Sartorelli 4, JHG Lago 4
  • 1Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, 09210 – 580, Brazil
  • 2Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, 05508 – 090, Brazil
  • 3Departamento de Micro, Imuno e Parasitologia, Universidade Federal de São Paulo, 04023 – 062 Brazil
  • 4Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, 09972 – 270, Brazil

The Lauraceae family presents mainly 50 genera in which the Nectandra, distributed at Central and South America, presenting 43 species recognized in Brazil [1]. Nectandra sp. showed to be composed by different metabolites such as phenylpropanoids, lignoids and alkaloids with several pharmacological activities [2,3]. In our previous study with hexane extract from leaves from N. leucantha, were isolated three compounds, dehydrodieugenol B (1) and its two other related derivatives 2 and 3 [4]. In continuation of this work, the CH2Cl2 phase from MeOH extract from leaves was subjected to purification over Sephadex LH-20 and prep. TLC to afford compound 4. Analysis of 1H and 13C NMR spectra of 4, including HMBC and HSQC, indicated structural similarity of 2, but containing an oxymethine carbon at δC75.1 assigned to C-7'. Analysis of HRESIMS, which displayed [M+Na]+ at m/z 379.1506 (calcd for C21H24O5Na, 379.1521), allowed the characterization of 4 as 1,2-dimethoxy-6-[2'-methoxy-4'-(7'-hydroxy-8'-propenyl)phenoxy]-4-(8-propenyl)benzene, a new natural product. In addition, compounds 3 and 4 were analyzed by circular dichroism, which presented positive and negative Cotton effect respectively, suggesting configuration (S)-3 and (R)-4 [5].

Fig. 1: Compounds 1 – 4 isolated from Nectandra leucantha leaves.

In vitro cytotoxic activity of compounds 1 – 4 were evaluated against B16F10 (murine melanoma), A2058 (human melanoma), HTC (human colon carcinoma), HeLa (human cervix carcinoma), SKBR-3 (human breast adenocarcinoma) and OVCAR-3 (human ovarian cancer) cell lines. Compound 1 and 3 were the most active, 1 being more active than combretastatin A4 (CA-4, standard drug) in some lineages with IC50 ranging from 25.9 ± 0.9 to 52.2 ± 5.0 µg/mL. Otherwise, compound 2 and 4 were inactives (IC50 > 100 µg/mL) to all cell lines. Therefore, it is possible to infer that cytotoxic activity of compounds 1-4 could be caused, at least in part, by the presence of free hydroxyl groups at aromatic ring in closely related structures.

Keywords: cytotoxic, Nectandra leucantha, Lauraceae, phenylpropanoids, dehydrodieugenol B

References:

[1] Rohwer, J.G. (1993) Lauraceae: Nectandra. Flora Neotropica, Monograph. The New York Botanical Garden, Volume 60. 2. Suarez et al. (1983) Phytochemistry 22: 609. 3. Santos Filho & Gilbert (1975) Phytochemistry 14: 821. 4. Grecco, et al.(2013) Cytotoxic phenylpropanoids from Nectandra leucantha Ness. (Lauraceae). Brazilian Conference on Natural Products, Natal, RN; 2013. 5. Reetz et al. (2000) Chirality 12:479 – 482.