Publication Title: 
Molecular and Biochemical Parasitology

Efforts to move from malaria control to eradication will require new approaches to block malaria transmission, such as the development of anti-malarial drugs with gametocytocidal activity. Here fluorescent oxidoreduction indicator alamarBlue is used to develop a screen for gametocyte viability. The fluorescent signal increases linearly with gametocyte number (R(2)=0.99) and determination of the IC(50) of epoxomicin demonstrated the assay was reproducible and sensitive (IC(50) 2.16±0.57 nM, Z'-factor 0.81±0.01).

Tanaka, Takeshi Q.
Williamson, Kim C.
Publication Title: 
Current Opinion in Biotechnology

Protein engineering of cytochrome P450 monooxygenases (P450s) has been very successful in generating valuable non-natural activities and properties, allowing these powerful catalysts to be used for the synthesis of drug metabolites and in biosynthetic pathways for the production of precursors of artemisinin and paclitaxel. Collected experience indicates that the P450s are highly 'evolvable' - they are particularly robust to mutation in their active sites and readily accept new substrates and exhibit new selectivities.

Jung, Sang Taek
Lauchli, Ryan
Arnold, Frances H.
Publication Title: 
Investigational New Drugs

Recent research suggests that altered redox control of melanoma cell survival, proliferation, and invasiveness represents a chemical vulnerability that can be targeted by pharmacological modulation of cellular oxidative stress. The endoperoxide artemisinin and semisynthetic artemisinin-derivatives including dihydroartemisinin (DHA) constitute a major class of antimalarials that kill plasmodium parasites through induction of iron-dependent oxidative stress.

Cabello, Christopher M.
Lamore, Sarah D.
Bair, Warner B.
Qiao, Shuxi
Azimian, Sara
Lesson, Jessica L.
Wondrak, Georg T.
Publication Title: 
The Journal of Antimicrobial Chemotherapy

OBJECTIVES: Indolone-N-oxides are characterized by the presence of a highly reactive pharmacophore, the nitrone moiety (C=N(+)-O(-)), which undergoes oxidation-reduction reactions.

Tahar, Rachida
Vivas, Livia
Basco, Leonardo
Thompson, Eloise
Ibrahim, Hany
Boyer, Jérémie
Nepveu, Françoise
Publication Title: 
Biological & Pharmaceutical Bulletin

Artemisinin exerts the antimalarial activity through activation by heme. The hemolysis in malaria results in the elevated levels of plasma heme which may affect the activity of artemisinin. We hypothesized that the extracellular heme would potentiate the antimalarial activity of artemisinin. Hemin (ferric heme) at the pathologic concentrations enhanced the activity of artemisinin against Plasmodium falciparum in vitro and increased the levels of the lipid peroxidation products in the presence of artemisinin.

Tangnitipong, Sunanta
Thaptimthong, Thitiporn
Srihirun, Sirada
Unchern, Supeenun
Kittikool, Dusadee
Udomsangpetch, Rachanee
Sibmooh, Nathawut
Publication Title: 
Journal of the American Chemical Society

The selective oxyfunctionalization of isolated sp(3) C-H bonds in complex molecules represents a formidable challenge in organic chemistry. Here, we describe a rational, systematic strategy to expedite the development of P450 oxidation catalysts with refined regio- and stereoselectivity for the hydroxylation of remote, unactivated C-H sites in a complex scaffold.

Zhang, Kaidong
Shafer, Brian M.
Demars, Matthew D.
Stern, Harry A.
Fasan, Rudi
Publication Title: 
FEBS letters

Artemisinin is an antimalarial sesquiterpenoid isolated from the aerial parts of the plant Artemisia annua. CYP71AV1, a cytochrome P450 monooxygenase was identified in the artemisinin biosynthetic pathway. CYP71AV1 catalyzes three successive oxidation steps at the C12 position of amorpha-4,11-diene to produce artemisinic acid. In this study, we isolated putative CYP71AV1 orthologs in different species of Artemisia.

Komori, Aya
Suzuki, Munenori
Seki, Hikaru
Nishizawa, Tomoko
Meyer, Jacobus Johannes Marion
Shimizu, Hideaki
Yokoyama, Shigeyuki
Muranaka, Toshiya
Publication Title: 
The Journal of Organic Chemistry

The Pd-catalyzed TBHP-mediated Wacker-type oxidation of internal alkenes is reported. The reaction uses 2-(4,5-dihydro-2-oxazolyl)quinoline (Quinox) as ligand and TBHP(aq) as oxidant to deliver single ketone constitutional isomer products in a predictable fashion from electronically biased olefins. This methodology is showcased through its application on an advanced intermediate in the total synthesis of the antimalarial drug artemisinin.

DeLuca, Ryan J.
Edwards, Jennifer L.
Steffens, Laura D.
Michel, Brian W.
Qiao, Xiaoxiao
Zhu, Chunyin
Cook, Silas P.
Sigman, Matthew S.
Publication Title: 
BioFactors (Oxford, England)

Natural leaves and flowers containing numerous aroma chemicals are widely used in aromatherapy since ancient times. In addition to their pleasant smells, aroma chemicals might have some beneficial health effects. Aroma extracts, isolated from coffee beans, soybeans, and mung beans by steam distillation under mild conditions (55 degrees C and 85 mm Hg) were examined for their antioxidative activities. The inhibitory effect of these extracts toward hexanal/hexanoic acid conversion was measured in the testing solution over prolonged time periods.

Lee, K. G.
Mitchell, A.
Shibamoto, T.
Publication Title: 
Asia Pacific Journal of Clinical Nutrition

The antioxidant effect of an aqueous extract of Phaseolus vulgaris pods, an indigenous plant used in Ayurvedic medicine in India, was studied in rats with streptozotocin-induced diabetes. Oral administration of Phaseolus vulgaris pod extract (PPEt; 200 mg/kg body weight) for 45 days resulted in a significant reduction in thiobarbituric acid reactive substances and hydroperoxides.

Venkateswaran, Subramanian
Pari, Leelavinothan


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