Enhancing water solubility of a drug (triptolide)

Gunda Georg and co-workers at the University of Minnesota reported in the Journal of Medicinal Chemistry on the addition of a phosphonooxymethyl group onto triptolide to increase its water solubility by greater than 3,580 times. (slight mistake: Scheme 2 in the paper has the use of benzoyl peroxide shown as “Bn2O2” when it should be “Bz2O2” – Bn2O2 would be benzyl peroxide). Another interesting point from this paper is that this natural product has multiple modes of action where it can covalently attach to proteins (XPB, xeroderma pigmentosum B) or non-covalently (DCTPP1, dCTP pyrophosphatase). Other modified attempts to form soluble prodrugs of this natural product (e.g. carboxylic acid, amino acid esters) resulted in difficult removal of the prodrug group.

J. Med. Chem. paper

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Arundic acid synthesis

Rodney Fernandes and co-workers from IIT Bombay have reported in European JOC on the synthesis of arundic acid.

European JOC paper

Jiadifenone

Miwa Kubo and co-workers at Tokushima Bunri University have reported in Tetrahedron Letters on some norsesquiterpenoids from Illicium jiadifengpi possessing neurotrophic activity.  This Illicium species is the same name that merrilactone came from (Illicium merrillianum)

TL paper

Theaflavins for Alzheimer’s and Parkinson’s

Jan Bieschke and co-workers at Washington University in St. Louis have reported in Biochemistry on the inhibition of theaflavins as inhibitors of amyloid-beta and alpha-synuclein fibrillogenesis.

Biochemistry paper

Dragmacidin D through C-H activation

Kenichiro Itami and co-workers from Nagoya University have reported in JACS on a synthesis of dragmacidin D using C-H activation as the strategy.

JACS paper

Proteomes vs. Disease

Theo Luider and colleagues at Erasmus Medical Center in the Netherlands have reported in the Journal of Proteome Research on the higher concentration of PZP (Pregnancy Zone Protein) in presymptomatic Alzheimer’s disease group of women.

Journal of Proteome Research paper

Sebestenoids

Philip Williams and co-workers at the University of Hawaii have reported in Phytochemistry on the isolation of sebestenoids.  Sebestenoid D had an IC50 value of 65 micromolar against BACE1 aspartic protease in the presence of detergent.

Phytochemistry paper

A protein responsible for enhancing memory?

Yadin Dudai and colleagues at the Weizmann Institute have reported in Science on a protein that is responsible for improving long term memory (PKMzeta).

 

Science paper

Nobiletin Studies

Toshiyuki Kan and co-workers at the University of Shizuoka and Global COE program have reported in Chem Comm on a total synthesis of nobiletin where they incorporated a 11C isotope to visualize the compound through PET (positron emission tomography) in order to see where it goes in the rat brain.  Nobiletin was found to enhance PKA/ERK/CREB signalling in rat hippocampal neurons.

Chem Comm paper

Some New Galbulimima Alkaloids

When I saw the term “galubulimima” I knew that the corresponding author was related to Lewis Mander – he and co-workers have recently isolated a new set of galubulimima alkaloids.

 

TL paper