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Hibiscus rosa-sinensis which belongs to the family Malvaceae, is a national flower of Malaysia. This glabrous tree can usually grow around 1 to 3 meters tall. The objective of present study was to categorize the essential oil constituent of flowers and leaves extract using different extraction method namely Soxhlet and hydrodistillation. The essential oil obtained from Soxhlet (10.75%) and hydrodistillation (11.40%) were subjected to Gas Chromatography-Mass Spectrometry (GC-MS) for determination of bioactive compounds. The GC-MS analysis was carried out by Agilent 7980A series GC instrument and DB-1MS capillary column with the dimensions of 30 m × 0.25 mm. A total of 21 and 20 compounds were identified for Soxhlet and hyrodistillation technique, respectively. Major compound found in essential oil for Soxhlet apparatus method was (Z,Z,Z)-9-12,15-Octadecatrienoic acid, methyl ester (23.59%) while for hydrodistillation was 1-Methylene-2b-hydroxymethyl-3,3-dimethyl-4b-(3-methylbut-2-enyl)-cyclohexane (16.57%). The presence of numerous bioactive compounds provides insights to the potential of the Hibiscus rosa-sinensis in pharmaceutical industry.

Therapeutic properties of the medicinal plant are due to the presence of phytochemical constituents. The phytochemical constituents of Plumeria alba flower were investigated by phytochemical screening assays and gas chromatography-mass spectrometry (GC-MS). The phytochemical screening of hexane, dichloromethane, ethyl acetate, butanol, and aqueous extracts of P. alba flower showed it contains a various concentration of saponins, flavonoids, tannins, steroids, volatile oil and phenolic compounds. Several major chemical constituents that were identified is squalene, bis(2-ethylhexyl) phthalate, methyl (methyl 4-O-methyl-α-d-mannopyranoside) uronate and tricyclo [7.2.0.0(2,6)] undecan-5-ol, 2,6,10,10-tetramethyl- (isomer 2) by using GC-MS technique.

Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62±0.61 and 4.44±0.66 µg/mL) and pinostrobin chalcone (2), (IC50 = 20.42±2.23 and 22.51±0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.

Biaryls are the potential source of synthetic drugs. The present study describes the synthesis of a series of functionalized biphenyl derivatives (3a-3g) using Pd-catalyzed Suzuki coupling reaction. The experimental results revealed the facile synthesis of biphenyl derivatives (3a-3g) with notably high yield (80-88%). Density functional theory (DFT) studies were performed by Gaussian 09 software in order to rationalize the selectivity of coupling at C-Br bond instead of C-Cl bond. In addition of synthesis, the biological activities (biofilm inhibition, hemolytic and anti-thrombolytic) of these novel compounds were investigated. These results exhibited good biofilm inhibition (5.86-65.8%), hemolytic (1.32-30.1%) and anti-thrombolytic activities (9.64-42.5%), indicating the potential use of these compounds for pharmaceutical applications

6-nitrobenzofuran-2-carbohydrazide Schiff base derivatives have been synthesized and their structure has been confirmed via H 1 NMR, Mass spectrometry and elemental (CHN/S) analysis. These synthesized analogs showed significant cytotoxic and antioxidant activity. Doxorubicin (IC 50 = 0.94 ± 0.20μM) and n -propyl gallate (IC 50 = 30.30 ± 0.40μM) were used as standard in cytotoxic and antioxidant activities, respectively. Compound 1 (IC 50 = 3.30 ± 0.90μM), 2 (IC 50 = 2.70 ± 0.25μM), 3 (IC 50 = 2.70 ± 0.25μM), 10 (IC 50 = 2.70 ± 1.10μM), 11 (IC 50 = 1.00 ± 1.20μM), and 17 (IC 50 = 3.75 ± 0.90μM) showed excellent while 21 (IC 50 = 7.50 ± 0.60μM) and 28 (IC 50 = 7.50 ± 0.66μM) showed moderate anti cancer activity. Furthermore, compound 10 (IC 50 = 17.50 ± 0.85μM), 11 ( IC 50 = 24.20 ± 0.55μM), 12 (IC 50 = 21.10 ± 1.58μM), 13 (IC 50 = 14.60 ± 0.32μM), 14 (IC 50 = 29.20 ± 0.75μM) and 15 (IC 50 = 9.26 ± 0.15μM) showed better antioxidant activity than the standard n -propyl gallate. This study will be useful to develop potential lead molecules with cytotoxic and antioxidant potential.

A chalcone derivative, (E)-3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)-prop-2-en-1-one (DMMF) was synthesized and evaluated against various cancerous cell lines including colon adenocarcinoma (HT-29), myloplasticleukemia (HL60), breast cancer (MCF-7 and MDA-MB231), normal hepatic cell (WRL-68) and normal breast cell (MCF-10A). The structure of DMMF was determined by EI-MS, 1H NMR and single X-ray crystallographic techniques. The DMMF possessed the highest cytotoxic effect against MCF-7 breast cancer cell (2.01 ± 1.53 μg/mL) and lowest against normal hepatic WRL-68 and breast cell lines after 24 h of treatment. Induction of apoptosis and regulation of cell cycle progression results indicates the significant increase in early apoptosis and G2/M arrest after 48 h of treatment in MCF-7 cells. Meanwhile, in MDA-MB231 cells, there was an increase in Sub G0/G1 cells population and early/late apoptotic cells upon treatment with DMMF. Additionally, DMMF effectively induced G2/M cell cycle arrest in MCF-7 cells and apoptosis in both MCF-7 and MDA-MB231 cells.

Curcumin is one of the promising natural products extracted from the rhizomes of curcuma longa and has been extensively investigated by researchers to explore its potential as a chemopreventive and therapeutic agent against several chronic diseases. To further enhance the cytotoxic potential of curcumin, its derivative (2E,6E)-2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC) has been synthesized and investigated, and its antitumor effect on tested on 4T1 challenged mice. BHMC was recorded with in vitro cytotoxicity on murine 4T1 breast cancer cells with IC50 value 13.66 μM, which was 2 times lower than curcumin after 72 hours of treatment. An in vivo study indicated that BHMC possessed antitumor effect on the 4T1 cells of the challenged mice by induction of apoptosis, antiproliferation, anti-inflammation and antimetastasis. This effect is better compared to curcumin treatment at the same evaluated concentration. Thus, BHMC is a potential antitumor agent against breast cancer.

Therapeutic properties of the medicinal plant are due to the presence of phytochemical constituents. Garciniaatroviridis is locally known as ?asamgelugur? belongs to the Guttiferae family. Bioassay-guided solvent-solvent extraction method and yielded, hexane, dichloromethane, ethyl acetate, butanol, and methanolic extracts. These extracts were used to investigate the presence of phytochemicals. The preliminary phytochemical screening showed the existence of fixed oils and fats, carbohydrate, saponins, phenolic, flavonoids and anthraquinone glycosides in G. atroviridis roots. The chemical compositions were investigated by using Gas Chromatography-Mass Spectroscopy (GC-MS). Major compound identified in hexane, DCM, EA, BuOH and methanolic extracts was (Z)-13-docosenoic acid methyl ester (24.32%), ethyl-9-hexadecenoate (6.36%),bis(1,3-diisopropylcyclopentadienyl) (12.09%), 2-methyl-2-phenyl- 1,3-dioxolane (2.34%) and furfural (33.55%) respectively. The antibacterial and antioxidant activities of the extracts were investigated. The methanolic crude extract exhibited resistance towards both bacteria tested; Bacillus subtilisand Escherichia coli, thus suggesting its antibacterial activity.

(2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.

Clinacanthus nutans has been used in traditional herbal medicine for cancer prevention, but the specific bioactive compounds responsible for the observed activities have not been explored. Different polar solvents such as methanol, chloroform, ethyl acetate, and hexane were used for the extraction. The extracts, fractions, and isolated compounds were subjected to DPPH and ferric reducing antioxidant potential (FRAP) assays. Methanol extracts show significant free-radical scavenging activity of 69.09% in DPPH and 56.49% FRAP. Purification of MeOH extracts afforded the fraction FB28 and two new sulfur-containing compounds, named clinamide D and E (1, 2). Compound (1) proved to be more active with an IC50 value for DPPH radical scavenging of 118.27 ± 0.01 µg/mL and reduction of Fe3+–TPTZ complex of 386.24 ± 0.02, higher than that of the standard ascorbic acid. Sulfur-containing compounds isolated from C. nutans is a potential natural antioxidant.

Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure–activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by 1H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.

Background Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies. Results Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1–10, acetone 11–17 and cyclopentanone 18–24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1–24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11–17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed 1H NMR, IR, UV–Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure–activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases. Conclusions Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.

Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1–10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20–14.38 lM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1–3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic

SweeKeong Yeap,1 Muhammad Nadeem Akhtar,2 Kian Lam Lim,3 Nadiah Abu,4,5 Wan Yong Ho,6 Seema Zareen,2 Kiarash Roohani,1 Huynh Ky,4 Sheau Wei Tan,1 Nordin Lajis,7 Noorjahan Banu Alitheen1,4 1Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 2Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia; 3Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor Darul Ehsan, Malaysia; 4Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 5Bright Sparks Unit, University of Malaya, Kuala Lumpur, Malaysia; 6School of Biomedical Sciences, University of Nottingham Malaysia Campus, Selangor Darul Ehsan, Malaysia; 7Scientific Chairs Unit, Taibah University, Medina, Saudi Arabia Abstract: Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2-carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel–Crafts condensation reaction. The mechanisms of cytotoxicity of DHAQC (2) in human breast cancer MCF-7 cells were further investigated. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DHAQC (2) exhibited potential cytotoxicity and selectivity in the MCF-7 cell line, comparable with the naturally occurring anthraquinone damnacanthal. DHAQC (2) showed a slightly higher IC50 (inhibitory concentration with 50% cell viability) value in the MCF-7 cell line compared to damnacanthal, but it is more selective in terms of the ratio of IC50 on MCF-7 cells and normal MCF-10A cells. (selective index for DHAQC (2) was 2.3 and 1.7 for damnacanthal). The flow cytometry cell cycle analysis on the MCF-7 cell line treated with the IC50 dose of DHAQC (2) for 48 hours showed that DHAQC (2) arrested MCF-7 cell line at the G2/M phase in association with an inhibited expression of PLK1 genes. Western blot analysis also indicated that the DHAQC (2) increased BAX, p53, and cytochrome c levels in MCF-7 cells, which subsequently activated apoptosis as observed in annexin V/propidium iodide and cell cycle analyses. These results indicate that DHAQC (2) is a synthetic, cytotoxic, and selective anthraquinone, which is less toxic than the natural product damnacanthal, and which demonstrates potential in the induction of apoptosis in the breast cancer MCF-7 cell line. Keywords: cytotoxic, selective index, cell cycle

The stem bark extracts of Knema laurina inhibited the hydrogen peroxide (H2O2)- and aggregated amyloid β-peptide 1-42 length (Aβ(1-42))-induced cell death in differentiated SH-SY5Y cells. Exposure of 250 μM H2O2 or 20 μM Aβ(1-42) to the cells for 24 h reduced 50% of cell viability. Pretreatment of cells with ethyl acetate extract (EAE) or n-butanol extract (BE) at 300 μg/mL and then exposure to H2O2 protected the cells against the neurotoxic effects of H2O2. Besides, methanolic extract (ME) at 1 and 10 μg/mL exerted neuroprotective effect on Aβ(1-42)-induced toxicity to the cells. These results showed that EAE, BE and ME exhibited neuroprotective activities against H2O2- and Aβ(1-42)-induced cell death. Flavonoids (3-6) and β-sitosterol glucoside (8) were isolated from the EAE. Compound 1 was isolated from hexane extract, and compounds 2 and 7 were isolated from dichloromethane extract. All these observations provide the possible evidence for contribution in the neuroprotective effects.

Aims Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability. Main methods A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels. Key findings DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9. Significance DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.

This study aims to evaluate the constituent compounds of plant extracts and their antimicrobial activity. Four different ethnomedicinal plant extracts including Piper nigrum, Nigella sativa, Cinnamomum zeylanicum, and Elettaria cardamomum were tested for antimicrobial susceptibility profile identified using GC-Mass and demonstrated TLC analysis. We found the combined action of ethanol plant extracts (alone) against oral isolates showed a synergistic effect profile up to 32.20% when combination A (Ci/Ca) was added. The stearic and palmitic acids were the major constituent compounds of plant extracts which was exhibited high antimicrobial susceptibility against the bacterial isolates. We conclude that the stearic and palmitic acids were major constituent compounds of plant extracts.

Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ± 0.21 and 8.50 ± 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.

Agarwood is well known as one of the expensive woods in the world. It has a unique scent which brings it to have wide usages especially in perfumery ingredient, as incense, in traditional medical preparation, and as symbol of wealth. Due to that, this paper presents the analysis on chemical profiles of agarwood chipwood, as a part of agarwood grading system. The work involved of Solid Phase Microextraction (SPME) coupled with Gas Chromatography — Mass Spectrometry (GC-MS) GC-MS in extracting high quality. Three headspace fibers; PDMS-DVB, CAR-PDMS and DVB-CAR-PDMS were used during the extraction to identify the compounds with the sampling time of 60 minutes. The result showed that high quality agarwood chipwood is made up of terpene group which are monoterpene hydrocarbon, sesquiterpene hydrocarbon and oxygenated sesquiterpene. The relative peak areas (%) for compounds are tabulated and plotted. The finding in this study confirmed that the difference in compounds extracted and their relative peak area (%) are due to different fiber's polarity and absorbent, Thus, it is significant and benefit especially in agarwood oil quality grading and its related area.

Due to its popularity and high market demand, critical analysis on agarwood vapour chemical compounds may provide an alternative quality discrimination of agarwood oil. The proposed work involves the extraction of high quality agarwood using headspace volatile divinylbenzene-carboxen-polydimethysiloxane (DVB-CAR-PDMS) solid phase microextraction (SPME) with different sampling time at 15, 30 and 60 minutes. Then, Gas chromatography — Mass Spectroscopy (GC-MS) is performed to identify the chemical compounds. Generally, agarwood vapour is rich in terpene group especially monoterpene, sesquiterpene and oxygenated sesquiterpene. Analysis showed that at least 52, 50 and 54 compounds are extracted at 15, 30 and 60 minutes, respectively. Among all, duration of 60 minutes produced the highest abundance (%) for caryophellene oxide. The finding proves that caryophellene oxide as one of the important compounds in high agarwood and different sampling time plays a major role that effects the extraction. Thus, the analysis in this study is significant and brings benefit especially to the agarwood and its essential oil research area.

The fritarillia imperialis is an ornamental flower that can be found in various parts of the world including Iraq, Afghanistan, Pakistan and the Himalayas. The use of this plant as traditional remedy is widely known. This study aims to unveil the anti-cancer potentials of Isopimara-7,15-Dien-19-Oic Acid, extracted from the bulbs of Fritillaria imperialis in cervical cancer cell line, HeLa cells. Flow cytometry analysis of cell death, gene expression analysis via cDNA microarray and protein array were performed. Based on the results, Isopimara-7,15-Dien-19-Oic acid simultaneously induced cell death and promoted cell survival. The execution of apoptosis was apparent based on the flow cytometry results and regulation of both pro and anti-apoptotic genes. Additionally, the regulation of anti-oxidant genes were up-regulated especially thioredoxin, glutathione and superoxide dismutase- related genes. Moreover, the treatment also induced the activation of pro-survival heat shock proteins. Collectively, Isopimara-7,15-Dien-19-Oic Acid managed to induce cellular stress in HeLa cells and activate several anti- and pro survival pathways.

A bioassay-guided investigation of Melicope ptelefolia Champ ex Benth (Rutaceae) resulted in the identification of an acyphloroglucinol, 2,4,6-trihydroxy-3-geranylacetophenone or tHGA, as the active principle inhibiting soybean 15-LOX. The anti-inflammatory action was also demonstrated on human leukocytes, where the compound showed prominent inhibitory activity against human PBML 5-LOX, with an IC(50) value of 0.42 μM, very close to the effect produced by the commonly used standard, NDGA. The compound concentration-dependently inhibited 5-LOX product synthesis, specifically inhibiting cysteinyl leukotriene LTC(4) with an IC(50) value of 1.80 μM, and showed no cell toxicity effects. The anti-inflammatory action does not seem to proceed via redox or metal chelating mechanism since the compound tested negative for these bioactivities. Further tests on cyclooxygenases indicated that the compound acts via a dual LOX/COX inhibitory mechanism, with greater selectivity for 5-LOX and COX-2 (IC(50) value of 0.40 μM). The molecular features that govern the 5-LOX inhibitory activity was thus explored using in silico docking experiments. The residues Ile 553 and Hie 252 were the most important residues in the interaction, each contributing significant energy values of -13.45 (electrostatic) and -5.40 kcal/mol (electrostatic and Van der Waals), respectively. The hydroxyl group of the phloroglucinol core of the compound forms a 2.56Å hydrogen bond with the side chain of the carboxylate group of Ile 553. Both Ile 553 and Hie 252 are crucial amino acid residues which chelate with the metal ion in the active site. Distorting the geometry of these ligands could be the reason for the inhibition activity shown by tHGA. The molecular simulation studies supported the bioassay results and served as a good model for understanding the way tHGA binds in the active site of human 5-LOX enzyme.

The ‘Ulam’, a traditional Malay dish, are plants that can be eaten raw, as a form of local salad. The shoots and young leaves of Melicope ptelefolia are among the popular species, believed to be high in nutritional and medicinal values. The metabolomic fingerprinting analysis of the ethanolic extracts of leaves of M. ptelefolia was carried out using 1 H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate data analysis in order to differentiate young and mature leaves and to evaluate the variation of their chemical composition. Principle component analysis (PCA) of the 1 H NMR spectra showed a clear discrimination between the young and mature leaves extracts by PC3 and PC4. The compounds responsible for the differentiation were identified by comparison of 1 H NMR chemical shifts and qualitative HPLC. The young leaves were found to be richer in fatty acids and the levels of the three marker compounds, p - O -geranylcoumaric acid, 2,4,6-trihydroxy-3-geranylacetophenone and 2,4,6-trihydroxy-3-prenylacetophenone, were clearly higher. The mature leaves contain higher levels of sugars and glycosidic components.

The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.

Two new triterpenoids, 18alpha,19beta-20(30)-taraxasten-3beta,21alpha-diol (cichoridiol) (1) and 17-epi-methyl-6-hydroxyangolensate (intybusoloid) (2), were obtained from the methanolic extract of seeds of Cichorium intybus along with 11 known compounds, lupeol (3), friedelin (4), beta-sitosterol (5), stigmasterol (6), betulinic acid (7), betulin (8), betulinaldehyde (9), syringic acid (10), vanillic acid (11) 6,7-dihydroxycoumarin (12), and methyl-alpha-D-galactopyranoside (13). Compounds 1, 1a, and 11 showed a good alpha-glucosidase inhibitory activity.

This paper presents a review on agarwood and its quality determination. It was found that Aquilaria Malaccensis is the main species in Malaysia and Indonesia. The agarwood has different quality or grades; similarly its essential oil. They are traded at different price according to their quality. Scientific reason showed that chemical compositions of agarwood make them different from each other, thus affect their quality. Physical appearances such as odour and colour have been used to grade their qualities. However the method has drawbacks in terms of subjectivity, poor reproducibility, time consumption and large labour expense. Therefore there is a requirement for agarwood and its oil to be graded according to their chemical profiles. This interest began to attract the researchers and also is mainly to ensure the quality of agarwood oil.

This paper presents the proposed Z-Score in identifying the significant chemical compounds of agarwood incense smoke. The technique is applied to commercial, low and high quality of agarwood samples and the extraction of the compounds were performed by gas chromatography — flame ion detector (GC-FID) and gas chromatography — mass spectrometry (GC-MS) coupled with solid phase microextraction (SPME) analysis. The Z-Score has successfully identified eight significant compounds in those qualities of agarwood smoke. They are β-maaliene, nor-ketoagarofuran, epoxybulnesene, 10-epi-γ-eudesmol, agarospirol, α-eudesmol, epi-α-bisabolol and rotundone. Among all, epoxybulnesene gave the highest abundant of 14.81%. The finding from this study showed that the chemical compounds for agarwood smoke is varied depending on their qualities. The identified compounds are useful for further study in agarwood smoke quality grading analysis

The stem bark extracts of Knema laurina inhibited the hydrogen peroxide (H2O2)- and aggregated amyloid β-peptide 1-42 length (Aβ(1-42))-induced cell death in differentiated SH-SY5Y cells. Exposure of 250 μM H2O2 or 20 μM Aβ(1-42) to the cells for 24 h reduced 50% of cell viability. Pretreatment of cells with ethyl acetate extract (EAE) or n-butanol extract (BE) at 300 μg/mL and then exposure to H2O2 protected the cells against the neurotoxic effects of H2O2. Besides, methanolic extract (ME) at 1 and 10 μg/mL exerted neuroprotective effect on Aβ(1-42)-induced toxicity to the cells. These results showed that EAE, BE and ME exhibited neuroprotective activities against H2O2- and Aβ(1-42)-induced cell death. Flavonoids (3-6) and β-sitosterol glucoside (8) were isolated from the EAE. Compound 1 was isolated from hexane extract, and compounds 2 and 7 were isolated from dichloromethane extract. All these observations provide the possible evidence for contribution in the neuroprotective effects.

The inhibitory effects of seven diterpenes, belonging to three different structural classes and isolated from the bark of Xylopia aethiopica, were investigated against the enzymes prolyl endopeptidase (PEP) and alpha-thrombin. Five compounds exhibited inhibitory activity against them.

Terminalin A 1, a new A-seco-triterpene, was isolated from the stem bark of Terminalia glaucescens Planchon. This compound has an unprecedented rearranged seco-glutinane structure with a pyran ring-A and an isopropanol moiety, as determined by spectroscopic and single-crystal X-ray diffraction analysis. Other known triterpenes, friedelin, β-sitosterol, stigmasterol, lupeol, betulinic acid, β-amyrin and long chain fatty acids were also isolated.

Bioassay-guided isolation of two new compounds, 3,4-methylenedioxy-3'-O-methyl-4'-O-glucoside ellagic acid (1) and the pteleoellagic acid derivative (2), from the stem bark of Pteleopsis hylodendron is reported along with 3,4-methylenedioxy-3'-O-methyl ellagic acid (3), 3,3'-di-O-methyl ellagic acid (4) and 3,3',4'-tri-O-methyl ellagic acid (5), which were obtained for the first time from this plant. The structures of these compounds were elucidated with the help of spectroscopic studies. Compounds 1 and 4 were found to have significant antioxidant activity, while compounds 1-4 showed antibacterial activity against different pathogenic bacteria.

The crystal structure of a pure sample of 9-(3-methyl­but-2-enyl­oxy)-7H-furo­[3,2-g]­chromen-7-one or imperatorin, C16H14O4, is composed of two independent mol­ecules with different conformations of the 3-methyl­butyl group. The structure of an impure sample of imperatorin has already been reported [Cox, Jaspars, Kumarasamy, Nahar, Sarker & Shoeb (2003). Acta Cryst. C59, o520–o522.]

Norlaily Mohd Ali,1 M Nadeem Akhtar,2 Huynh Ky,3 Kian Lam Lim,1 Nadiah Abu,4 Seema Zareen,2 Wan Yong Ho,5 Han Kiat Alan-Ong,1 Sheau Wei Tan,6 Noorjahan Banu Alitheen,4 Jamil bin Ismail,2 Swee Keong Yeap,6 Tunku Kamarul7 1Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, 2Department of Industrial Biotechnology, Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Pahang, Malaysia; 3Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, CanTho City, Vietnam; 4Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 5School of Biomedical Sciences, The University of Nottingham Malaysia Campus, 6Institute of Bioscience, Universiti Putra Malaysia, Selangor, 7Tissue Engineering Group, National Orthopaedic Centre of Excellence for Research and Learning, Department of Orthopaedic Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia Abstract: Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet (1H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 µM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 µM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cell treated with 36 µM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time point was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cell were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group)on ring B structure contributed to the selective cytotoxicity against MCF-7 cell compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as new anticancer drug. Keywords: (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS), MCF-7, G2/M arrest, apoptosis, cell cycle, PLK-1, p53, caspase

This paper presents the application of Solid Phase Micro Extraction (SPME) coupled with Gas Chromatography-Mass Spectrometry (GC-MS) and Gas Chromatography-Flame Ionization Detector (GC-FID) to charaterize agarwood incense. The work involved three types of SPME fibres at 30 minutes sampling time. The fibres are 50/30 µm divinylbenzene-carboxen­polydimethysiloxane (DVB-CAR-PDMS), 65 µm polydi methylsiloxane­divinylbenzene (PDMS-DVB) and 85 µm carboxen-polydimethyl siloxane (CAR-PDMS). The results showed that among many compounds extracted by GC-MS coupled with SPME, six compounds were found significantly presence in high quality aganvood incense due to their high percentage area (%). They are beta-maaliene, alpha-elemol, beta-selinene, 10-epi-gamma-eudesmol, agarospirol and caryophellene oxide. The finding offers a new approach for establishing the volatile profile of agarwood incense components which is beneficial for agarwood grading and discrimination.

Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics.

The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.

From the stem bark of Pteleopsis hylodendron, a triterpenoidal saponin bellericagenin [B 3-O-[beta-D-glucopyranosyl-(1-->2)-alpha-D-glucopyranoside] (1) (Pteleopsoside)] and two sphingolipids, hylodendroside-I (2), and hylodendroside-II (3) were isolated, along with a synthetically known compound, [2alpha, 3beta, 23-triacetoxy-19alpha-hydroxyolean-12-en-28-oic acid (4)]. Other known compounds, friedelin (5), beta-carotene (6), lupeol (7), sitosterol (8), and stigmasterol (9), were also obtained. Their structures were deduced with the help of detailed spectroscopic studies.

An unexpected dinitro derivative (2) of sesquiterpene lactone achillin (1), isolated from the aerial part of Achilleu micrantha Wild., was formed when this compound was exposed to gaseous NOClin CHCl 3 . This derivative was transformed into dinitrocarbonic acid (3) in pyridine in 30 minutes and in quantitative yield. The structures of these compounds were unambiguously determined by single-crystal X-Ray diffraction analysis.

Background Hyaluronidases have been found as the target enzymes in the development of osteoarthritis (OA) disease. While there is still no curative treatment for this disease, recent studies on the treatment of OA were focused on the effectiveness of natural products which are expected to improve the symptoms with minimal side effects. The aim of this study was to screen selected Malaysian plants on their anti-hyaluronidase activity as well as to evaluate the active plant and its derived fractions on its potential anti-arthritic and antioxidant activities. Methods A total of 20 methanolic crude extracts (bark and leaf) from ten different plants were screened using a colorimetric hyaluronidase enzymatic assay. The active plant extract (Payena dasyphylla) was then studied for its hyaluronidase inhibitory activity in the interleukin-1β (IL-1β) stimulated human chondrocytes cell line (NHAC-kn) using zymography method. The Payena dasyphylla methanolic bark extract was then fractionated into several fractions in where the ethyl acetate (EA) fraction was evaluated for its inhibitory effects on the HYAL1 and HYAL2 gene expressions using reverse transcription-polymerase chain reaction (RT-PCR) technique. While the MMP-3 and MMP-13 protein expressions were evaluated using western blot method. The phenolic and flavonoid contents of the three fractions as well as the antioxidant property of the EA fraction were also evaluated. Results Bark extract of Payena dasyphylla (100 μg/ml) showed the highest inhibitory activity against bovine testicular hyaluronidase with 91.63%. The plant extract also inhibited hyaluronidase expression in the cultured human chondrocyte cells in response to IL-1β (100 ng/ml). Similarly, treatment with Payena dasyphylla ethyl acetate ( EA) fraction (100 μg/ml) inhibited the HYAL1 and HYAL2 mRNA gene expressions as well as MMP-3 and MMP-13 protein expression in a dose dependent manner. Payena dasyphylla EA fraction has demonstrated the highest amount of phenolic and flavonoid content with 168.62 ± 10.93 mg GAE/g and 95.96 ± 2.96 mg RE/g respectively as compared to water and hexane fractions. In addition, the Payena dasyphylla EA fraction showed strong antioxidant activity with IC50 value of 11.64 ± 1.69 μg/mL. Conclusion These findings have shown that Payena dasyphylla might contained potential phenolic compounds that inhibiting the key enzyme in osteoarthritis development, which is the hyaluronidase enzyme through interruption of HYAL1 and HYAL1 gene expressions. The degradation of cartilage could also be inhibited by the plant through suppression of MMP-3 and MMP-13 protein expressions. We also reported that the inhibitory effect of Payena dasyphylla on hyaluronidase activity and expression might be due to its anti-oxidant property.

A new triterpenoid, glaucinoic acid (2α, 3β, 19α, 24-tetrahydroxyolean-12-en-30-oic acid) (1) along with several known compounds, arjunic acid (2), arjungenin (3), sericoside (4), and friedelin (5) were isolated from the stem barks of Terminalia glaucescens. These compounds showed β - glucuronidase inhibitory activity. The structures were identified on the basis of spectroscopic techniques