Crystallography, X-Ray

Publication Title: 
Biophysical Journal

In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe) and nitrous oxide (N(2)O) act by blocking the N-methyl-d-aspartate (NMDA) receptor. Using x-ray crystallography, we examined the binding characteristics of these two gases on two soluble proteins as structural models: urate oxidase, which is a prototype of a variety of intracellular globular proteins, and annexin V, which has structural and functional characteristics that allow it to be considered as a prototype for the NMDA receptor. The structure of these proteins complexed with Xe and N(2)O were determined.

Colloc'h, Nathalie
Sopkova-de Oliveira Santos, Jana
Retailleau, Pascal
Vivarès, Denis
Bonneté, Françoise
Langlois d'Estainto, Béatrice
Gallois, Bernard
Brisson, Alain
Risso, Jean-Jacques
Lemaire, Marc
Prangé, Thierry
Abraini, Jacques H.
Publication Title: 
Protein Science: A Publication of the Protein Society

Glutathione S-transferase of the malarial parasite Plasmodium falciparum (PfGST) represents a novel class of GST isoenzymes. Since the architecture of the PfGST substrate binding site differs significantly from its human counterparts and there is only this one isoenzyme present in the parasite, PfGST is considered a highly attractive target for antimalarial drug development. Here we report the mechanistic, kinetic, and structural characterization of PfGST as well as its interaction with different ligands.

Hiller, Nicole
Fritz-Wolf, Karin
Deponte, Marcel
Wende, Wolfgang
Zimmermann, Herbert
Becker, Katja
Publication Title: 
Molecules (Basel, Switzerland)

Since its identification in the early 1970s, artemisinin, as well as semi-synthetic derivatives and synthetic trioxanes, have been used in malaria therapy. Reduction of artemisinin by NaBH4 produced dihydroartemisinin (DHA), and yielded a new stereochemically labile centre at C-10, which, in turn, provided two interconverting lactol hemiacetal epimers (namely alpha and beta), whose rate of interconversion depends on buffer, pH, and solvent polarity.

D'Acquarica, Ilaria
Gasparrini, Francesco
Kotoni, Dorina
Pierini, Marco
Villani, Claudio
Cabri, Walter
Di Mattia, Michela
Giorgi, Fabrizio
Publication Title: 
Bioorganic & Medicinal Chemistry Letters

Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally.

Moon, Deuk Kyu
Tripathi, Abhai
Sullivan, David
Siegler, Maxime A.
Parkin, Sean
Posner, Gary H.
Publication Title: 
Chemical & Pharmaceutical Bulletin

In an attempt to develop potent and selective anti-tumor agents, two novel series of artemisinin-chalcone hybrids were designed, synthesized and screened for their antitumor activities against HT-29, A549, MDA-MB-231, HeLa and H460 cell lines in vitro. Nearly all of the tested compounds showed significantly increased anti-tumor activity compared with the corresponding dihydroartemisinin (DHA). Most of the title compounds displayed good selectivity toward HT-29 and HeLa cell lines with IC?? values ranging from 0.09 to 0.85 µM.

Xie, Lijun
Zhai, Xin
Ren, Lixiang
Meng, Haiyan
Liu, Chun
Zhu, Wufu
Zhao, Yanfang
Publication Title: 
Malaria Journal

BACKGROUND: Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile.

Becker, John V. W.
van der Merwe, Marina M.
van Brummelen, Anna C.
Pillay, Pamisha
Crampton, Bridget G.
Mmutlane, Edwin M.
Parkinson, Chris
van Heerden, Fanie R.
Crouch, Neil R.
Smith, Peter J.
Mancama, Dalu T.
Maharaj, Vinesh J.
Publication Title: 
International Journal of Pharmaceutics

Artemether (AM) plus azithromycin (AZ) rectal co-formulations were studied to provide pre-referral treatment for children with severe febrile illnesses in malaria-endemic areas. The target profile required that such product should be cheap, easy to administer by non-medically qualified persons, rapidly effective against both malaria and bacterial infections. Analytical and pharmacotechnical development, followed by in vitro and in vivo evaluation, were conducted for various AMAZ coformulations.

Gaubert, Alexandra
Kauss, Tina
Marchivie, Mathieu
Ba, Boubakar B.
Lembege, Martine
Fawaz, Fawaz
Boiron, Jean-Michel
Lafarge, Xavier
Lindegardh, Niklas
Fabre, Jean-Louis
White, Nicholas J.
Olliaro, Piero L.
Millet, Pascal
Grislain, Luc
Gaudin, Karen
Publication Title: 
Acta Poloniae Pharmaceutica

Artemisinin (ARMN) is a potent antimalarial drug, which is effective against multidrug resistant strains of Plasmodium falciparum and produces rapid recovery even in patients with cerebral malaria. Being poorly soluble in water, artemisinin is incompletely absorbed after oral intake due to poor dissolution characteristics in the intestinal fluids. To enhance these properties, solid dispersions of artemisinin with succinic acid (SUC) were prepared using drug-carrier ratios 1 : 1, 1 : 4, 1 : 6, 1 : 8 and 1 : 10 by solvent evaporation and freeze drying methods.

Ansari, Muhammad Tayyab
Pervez, Humayun
Shehzad, Muhammad Tariq
Saeed-ul-Hassan, Syed
Mehmood, Zahid
Shah, Syed Nisar Hussain
Razi, Muhammad Tahir
Murtaza, Ghulam
Publication Title: 

An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose.

Sim, Lyann
Jayakanthan, Kumarasamy
Mohan, Sankar
Nasi, Ravindranath
Johnston, Blair D.
Pinto, B. Mario
Rose, David R.
Publication Title: 
Planta Medica

The gum resin of Commiphora wightii [(Hook. ex Stocks) Engl.] is an ayurvedic medicine for the treatment of arthritis, inflammation, obesity, lipid disorders, and cardiovascular diseases and is known as guggul. Morphologically, it is not easy to distinguish guggul from closely related gum resins of other plants. Reliability of the commercially available guggul is critical due to the high risk of adulteration.

Ahmed, Rida
Ali, Zulfiqar
Wu, Yunshan
Kulkarni, Swapnil
Avery, Mitchell A.
Choudhary, Muhammed Iqbal
Khan, Ikhlas A.


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