Reaction Kinetics of the Benzylation of Adenine in DMSO: Regio-Selectivity Guided by Entropy.

The factors governing the regio-selectivity of the alkylation of adenine have been of interest for many years due to the biological importance of adenine derivatives, however, no reaction kinetic studies have been conducted. Herein, we report the rate constants and activation parameters of the benzylation of adenine under basic conditions in DMSO in the absence and presence of 15-crown-5 ether using real-time H NMR spectroscopy. The reaction is second-order for the formation of the N9- and N3-benzyladenine products, with a regio-selectivity factor 2.

A Water-Soluble Polymer-Lumefantrine Conjugate for the Intravenous Treatment of Severe Malaria.

Uncomplicated malaria is effectively treated with oral artemisinin-based combination therapy (ACT). Yet, there is an unmet clinical need for the intravenous treatment of the more fatal severe malaria. There is no combination intravenous therapy for uncomplicated due to the nonavailability of a water-soluble partner drug for the artemisinin, artesunate.

Coordination Sites for Sodium and Potassium Ions in Nucleophilic Adeninate Contact ion-Pairs: A Molecular-Wide and Electron Density-Based (MOWED) Perspective.

The adeninate anion (Ade) is a useful nucleophile used in the synthesis of many prodrugs (including those for HIV AIDS treatment). It exists as a contact ion-pair (CIP) with Na and K (M) but the site of coordination is not obvious from spectroscopic data. Herein, a molecular-wide and electron density-based (MOWED) computational approach implemented in the implicit solvation model showed a strong preference for bidentate ion coordination at the N3 and N9 atoms.

Development of a mycolic acid-graphene quantum dot probe as a potential tuberculosis biosensor.

The development of amine-functionalized graphene quantum dots (GQDs) linked to mycolic acids (MAs) as a potential fluorescent biosensor to detect tuberculosis (TB) biomarkers is described. GQDs have attractive properties: high fluorescence, excellent biocompatibility, good water solubility, and low toxicity. MAs are lipids that are found in the cell wall of Mycobacterium tuberculosis that are antigenic, however, they are soluble only in chloroform and hexane.

Synthesis and characterisation of quantum dots coupled to mycolic acids as a water-soluble fluorescent probe for potential lateral flow detection of antibodies and diagnosis of tuberculosis.

This work explores the potential use of cadmium-based quantum dots (QDs) coupled to mycolic acids (MAs) as a fluorescent probe to detect anti-MA antibodies which are biomarkers for tuberculosis (TB). The use of free MAs as antigens for the serodiagnosis of TB is known but has not been developed into a point of care test. This study focuses on the synthesis, solubility, and lateral flow of QDs coupled to MAs.

Towards a Molecular Understanding of Cation-Anion Interactions and Self-aggregation of Adeninate Salts in DMSO by NMR and UV Spectroscopy and Crystallography.

Rare anionic forms of nucleic acids play a significant biological role and lead to spontaneous mutations and replication and translational errors. There is a lack of information surrounding the stability and reactivity of these forms. Ion pairs of mono-sodium and -potassium salts of adenine exist in DMSO solution with possible cation coordination sites at the N1, N7 and N9 atoms of the purine ring.

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells.

Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG-BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG-BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways.

Synthesis, physicochemical characterization, toxicity and efficacy of a PEG conjugate and a hybrid PEG conjugate nanoparticle formulation of the antibiotic moxifloxacin.

Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells.

Nanomedicines for Malaria Chemotherapy: Encapsulation vs. Polymer Therapeutics.

Malaria is one of the oldest infectious diseases that afflict humans and its history extends back for millennia. It was once prevalent throughout the globe but today it is mainly endemic to tropical regions like sub-Saharan Africa and South-east Asia. Ironically, treatment for malaria has existed for centuries yet it still exerts an enormous death toll.

Design, synthesis and anticancer activity of Michael-type thiol adducts of α-santonin analogue with exocyclic methylene.

A series of Michael-type analogues were generated on the C-ring of α-santonin (α-methylene-γ-butyrolactone) upon reaction with various thiols. All the thiol adducts synthesized were evaluated for their anticancer activity against four human cancer cell lines (PC-3, HCT-15, A-549 and MCF-7). Bioassay results indicated that even though most of the synthesized compounds exhibited a good anticancer activity against various cancer cells in vitro, some of the compounds like 9e, 9g and 9q were found to be the most promising analogues in this series, with compound 9e showing IC50 values of 1.

Anticancer agents from diverse natural sources.

This review attempts to portray the discovery and development of anticancer agents/drugs from diverse natural sources. Natural molecules from these natural sources including plants, microbes and marine organisms have been the basis of treatment of human diseases since the ancient times. Compounds derived from nature have been important sources of new drugs and also serve as templates for synthetic modification.