Dya Fita Dibwe

Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy.

A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC(50), 0.49 μM), diethoxy derivative 4h (PC(50), 0.66 μM), and triethoxy derivative 4m (PC(50), 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC(50), 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy.

Cassane diterpenes from the seed kernels of Caesalpinia sappan

Eight structurally diverse cassane diterpenes named tomocins A-H were isolated from the seed kernels of Vietnamese Caesalpinia sappan Linn. Their structures were determined by extensive NMR and CD spectroscopic analysis. Among the isolated compounds, tomocin A, phanginin A, F, and H exhibited mild preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived condition without causing toxicity in normal nutrient-rich conditions.

Damnacanthal from the Congolese Medicinal Plant Garcinia huillensis has a Potent Preferential Cytotoxicity against Human Pancreatic Cancer PANC‐1 Cells

Screening of eight Congolese medicinal plants showed that the CHCl3 and MeOH extracts of Aframomum melegueta (PC50 = 47.8 µg/mL and 13.8 µg/mL, respectively) and CHCl3 extracts of Garcinia huillensis (PC50 = 17.8 µg/mL) and Securidaca longepedunculata (PC50 = 23.4 µg/mL) had preferential cytotoxicity against human pancreatic cancer PANC‐1 cells under nutrient‐deprived conditions. The active constituents of the CHCl3 extract of G. huillensis were examined and 12 known anthraquinones were identified. Among them, damnacanthal (1) caused preferential necrotic cell death of PANC‐1 and PSN‐1 cells under nutrient‐deprived and serum‐sensitive conditions (PC50 = 4.46 µm and 3.77 µm, respectively). Copyright

Heptaoxygenated xanthones as anti-austerity agents from Securidaca longepedunculata.

In a course of our search for anticancer agent based on a novel anti-austerity strategy, we found that the CHCl3 extract of the roots of Securidaca longepedunculata (Polygalaceae), collected at Democratic Republic of Congo, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation on the CHCl3 extract led to the isolation of 28 compounds including five new polymethoxylated xanthones [1,6,8-trihydroxy-2,3,4,5-tetramethoxyxanthone (1), 1,6-dihydroxy-2,3,4,5,8-pentamethoxyxanthone (2), 8-hydroxy-1,4,5,6-tetramethoxy-2,3-methylenedioxyxanthone (3), 4,6,8-trihydroxy-1,2,3,5-tetramethoxyxanthone (4), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (5)] and a new benzyl benzoate [benzyl 3-hydroxy-2-methoxybenzoate (6)]. Among them, 1,6,8-trihydroxy-2,3,4,5-tetramethoxyxanthone (1) and 1,6-dihydroxy-2,3,4,5,8-pentamethoxyxanthone (2) displayed the potent preferential cytotoxicity with PC50 of 22.8 and 17.4 μM, respectively. They triggered apoptosis-like PANC-1 cell death in NDM with a glucose-sensitive mode.

Constituents of the Rhizomes of Boesenbergia pandurata and Their Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Line

Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 6.6 μg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1-8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC50 values of 1.0 and 0.84 μM, respectively.

Uvaridacols E−H, Highly Oxygenated Antiausterity Agents from Uvaria dac

Chemical investigation of the stems of Uvaria dac yielded four new highly oxygenated cyclohexene derivatives named uvaridacols E-H (1-4). Their structures were established through NMR and circular dichroism spectroscopic analysis. Uvaridacols E (1), F (2), and H (4) displayed weak preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions in a concentration-dependent manner, without causing toxicity in normal nutrient-rich conditions.

Anti-austerity agents from Rhizoma et Radix Notopterygii (Qianghuo).

During a search for potent anticancer agents from natural products based on an anti-austerity strategy, we found that a CHCl3 extract of Rhizoma et Radix Notopterygii (Qianghuo), a Chinese crude drug, exhibited strong cytotoxicity against PANC-1 human pancreatic cancer cells, with a PC₅₀ value of 17.5 µg/mL. Further fractionation and purification of this bioactive extract led to the isolation of 19 known compounds. The in vitro preferential cytotoxicity of the isolates was evaluated against two human pancreatic cancer cell lines, PANC-1 and PSN-1. Among the compounds isolated, ostruthin displayed the most potent activity against both PANC-1 (PC₅₀, 7.2 µM) and PSN-1 (PC₅₀, 7.8 µM) cells in nutrient-deprived medium (NDM) and may have induced necrotic nutrient-deprived PANC-1 cell death.

Muchimangins G–J, Fully Substituted Xanthones with a Diphenylmethyl Substituent, from Securidaca longepedunculata

Four highly oxygenated xanthones, muchimangins G-J (1-4), have been isolated from the roots of Securidaca longepedunculata collected in Democratic Republic of Congo. Their structures were elucidated by analyses of spectroscopic data to be fully substituted xanthones with a diphenylmethyl substituent at C-2.

A new polyoxygenated cyclohexane and other constituents from Kaempferia rotunda and their cytotoxic activity

A new polyoxygenated cyclohexane and other constituents from Kaempferia rotunda and their cytotoxic activity Subehan Lallo, Sullim Lee, Dya Fita Dibwe, Yasuhiro Tezuka & Hiroyuki Morita a Faculty of Pharmacy, Biofarmaka Research Center, Hasanuddin University, Jl. Perintis Kemerdekaan Km 10, Makassar, 90245, Indonesia b Institute of Natural Medicine, University of Toyama, 2630Sugitani, Toyama, 930-0194, Japan c Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa, 920-1181, Japan Published online: 11 Aug 2014.The isolation of secondary metabolites from a methanolic extract of Kaempferia rotunda yielded 12 compounds (1–12), including a new polyoxygenated cyclohexane compound, (–)-3-acetyl-4-benzoyl-1-benzoyloxymethyl-1,6-diepoxycyclohexan-2,3,4,5-tetrol (1). The structures of the isolated compounds were determined based on their spectroscopic data and comparison with references. All of the isolated compounds were tested for their cytotoxic activity against pancreatic (PSN-1) and breast (MDA-MB231) cancer cell lines. Compound 12 showed moderate cytotoxic activity against PSN-1 and MDA-MB231 without showing any cytotoxicity against the normal cell line, TIG-3.

Highly oxygenated antiausterity agents from the leaves of Uvaria dac

From the chloroform extract of the leaves of Uvaria dac, four new highly-oxygenated cyclohexene derivatives named uvaridacols I-L (1-4) were isolated together with nine previously reported compounds (5-13). Their structures were determined based on the extensive NMR spectroscopic data and circular dichroism spectroscopic analysis. Among the new compounds, uvaridacol L (4) displayed strong preferential cytotoxicity in the nutrient deprived medium against five different tested pancreatic cancer cell lines, PANC-1 (PC50, 20.1μM), PSN-1 (PC50, 9.7μM), MIA PaCa-2 (PC50, 29.1μM), Capan-1 (73.0μM) and KLM-1 (25.9μM).