Send Orders of Reprints at bspsaif@emirates.net.ae Combinatorial Chemistry & High Throughput Screening, 2013, 16, 000-000 1 1386-2073/13 $58.00+.00 © 2013 Bentham Science Publishers Flavonoids and Linderone from Lindera oxyphylla and their Bioactivities Masoumeh Hosseinzadeh 1 , A. Hamid A. Hadi *,1 , Jamaludin Mohamad 2 , Mohammad A. Khalilzadeh *,3 , Shiau-Chuen Cheahd 4 and Mehran Fadaeinasab 1 1 Centre for Natural Products and Drug Discovery, Block D, Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia 2 Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia 3 Department of Chemistry, Science and research Branch, Islamic Azad University, Mazandaran, Iran 4 Centre of Natural Products & Drug Discovery Research (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Abstract: A new linderone A, namely 2-cinnamoyl-3-hydroxy-4, 5-dimethoxycyclopenta-2, 4-dienone (5), together with three known flavonoids (1-3) and one linderone (4), were isolated from the bark of Lindera oxyphylla. Extensive spectroscopic analysis including 1D and 2D-NMR spectra determined their sturctures. In addition, the antioxidant activity of all the compounds has been determined using 2, 2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferric reducing antioxidant power (FRAP) and ferrous ion chelating (FIC) methods. Compound 3 showed excellent DPPH scavenging activity with IC 50 % value of 8.5 ± 0.004% (g/mL) which is comparable with vitamin C. This compound, also showed an absorbance value of 1.00 ± 0.06% through FRAP test when compared with Butyl Hydroxy Aniline (BHA). However, FIC showed low activity for all the isolated compounds (chelating activity less than 50%) in comparison with ethylene diamine tetra acetic acid (EDTA). Anticancer activity for all compounds has also been measured on A375 human melanoma, HT-29 colon adenocarcinoma, MCF-7 human breast adenocarcinoma cells, WRL-68 normal hepatic cells, A549 non-small cell lung cancer cells and PC-3 prostate adenocarcinoma cell line. Compound 1 showed A549=65.03%, PC-3=30.12%, MCF-7=47.67, compound 2 showed PC-3=90.13%, compound 3 showed MCF-7=79.57 and for compound 5 MCF-7 is 96.33. Keywords: Anticancer activity, antioxidant activity, flavonoid, Lindera oxyphylla, linderone A. INTRODUCTION In the temperate regions of Asia and the Midwest of United States the plants of genus Lindera (Lauraceae) are mainly distributed in tropical, subtropical regions. The plant has around 100 species. The Chinese traditionally used to treat stomach, urinary system diseases and rheumatic pain with this plant [1]. Lindera oxyphylla belongs to a Lindera genus which contains more flavonoids and linderone [2, 3]. It is reported that Flavonoids exhibit multiple biological effects such as antiviral [4], antibacterial [5], anti- inflammatory [6, 7], vasodilator [8], anticancer [9], anti- ischemic [10-12] and antioxidant properties [13]. Sesquiterpenoids [14], alkaloids [15], lignans [16], anolides [17] and unique cyclopentenedione derivatives have already been coveredin previous chemical investigations on Lindera species. Pharmacological studies on this plant have revealed various bioactivities such as antioxidation [18], protection against post-ischemic myocardial dysfunction, antiviral *Address correspondence to these authors at the (Masoumeh Hosseinzadeh) Centre for Natural Products and Drug Discovery, Block D, Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; E-mail: ahamid@um.edu.my and (A. Hamid A. Hadi) Department of Chemistry, Science and research Branch, Islamic Azad University, Mazandaran, Iran; Tel: 603-79674010; Fax: 603-79674193; E-mail: khalilzadeh73@yahoo.com (SARS associated coronavirus) activity, cytotoxicity and slowing the progression of diabetic nephropathy in db/db mice [19]. To our knowledge, no information is available on the antioxidant and antibacterial properties of the extract of Lindera oxyphylla. A phytochemical study was successfully performed on the barks of Malaysian Lauraceae, and Lindera oxyphylla, and isolated compounds 1-5 (Fig. 1), with three flavonoids (1-3) and two linderones (4, 5) compounds. Amongst all, compound 5 with namely 2-cinnamoyl-3- hydroxy-4, 5-dimethoxycyclopenta-2, 4-dienone has been reported here for the first time. No other structure with this skeleton has been reported to date. This paper presented the results of the antioxidant activities using DPPH, FRAP, FIC, as well as anticancer activities using A549, A375, WRL-68, PC-3, HT-29, and MCF-7. RESULT AND DISCUSSION Identification of Compounds (1-5) Compounds of 1 to 4 had been identified at past researches. Compound 1: (+)-Onysilin with IUPAC name [(2S)-5- hydroxy -6, 7-dimethoxy-2-phenyl chroman-4H-one, LC-MS spectrum showed an intense pseudomolecular ion peak, [M+H]  at m/z 301.0824 corresponding to the molecular