Lise-Lotte Gundersen

9-Benzylpurines with inhibitory activity against Mycobacterium tuberculosis

9-Benzylpurines with a variety of substituents in the 2-, 6- and/or 8-position have been prepared and screened for antimycobacterial effects. High inhibitory activity against Mycobacterium tuberculosis was found for 9-benzylpurines carrying a phenylethynyl-, trans-styryl or aryl substituents in the 6-position and generally chlorine in the 2-position tends to increase activity.

Synthesis of 1-substituted 7-cyano-2,3-diphenylindolizines and evaluation of antioxidant properties

Protocols for the synthesis of novel 1-substituted 7-cyano-2,3-diphenylindolizines from the corresponding indolizinol have been developed, and the compounds’ abilities to act as antioxidants, i.e. To inhibit lipid peroxidation in vitro, have been examined. 1-bromo-7-cyano-2,3-diphenylindolizine 9 readily participates in pd-catalysed coupling reactions with organotin, organozinc, and organoboron reagents. Similar treatment of the corresponding indolizinyl triflate 6, on the other hand, resulted only in partial cleavage of the triflate back to the indolizinol, except in reaction with 1-ethoxyethenyl(tributyl)tin. Here, the unexpected acetal (1-ethoxyethoxy)indolizine 10 was formed. The structure of 10 was determined by single-crystal x-ray diffraction methods at 150 k. An alternative strategy for the introduction of substituents at c-1 is by lithiation of the bromide 9 followed by reaction with electrophiles. The ability of the indolizine derivatives to inhibit lipid peroxidation in vitro was examined. Lipid peroxidation of boiled rat liver microsomes was induced by ascorbic acid/feso4 and peroxidation was determined by measuring the material reactive to thiobarbituric acid. In particular, the indolizinyl acetate 4 and the triflate 6 appear to be highly active antioxidants, with ic50 values below 1 µm in the bioassay.

6-Halopurines in palladium-catalyzed coupling with organotin and organozinc reagents

Abstract N-9 and N-7 benzylated 6-halopurines readily participate in palladium catalyzed cross coupling reactions with organotin and organozinc derivati

Regiochemistry in Stille couplings of 2,6-dihalopurines

Abstract The regiochemistry in Stille couplings of 2,6-dihalopurines have been studied. 2,6-Dichloropurines react selectively in the 6-position, and 6-chloro-2-iodopurines and 2-bromo-6-chloropurines in the 2-position.

Synthesis of 6-alkenyl- and 6-alkynylpurines with cytokinin activity

Abstract Analogs of the cytokinins trans -zeatin and benzylaminopurine have been prepared by Heck coupling on 6-vinylpurines or Sonogashira coupling on 6-halopurines as key-steps, and their cytokinin activity has been evaluated based on their ability to stimulate increased growth in radish cotyledons.

Regioselective N-9 arylation of purines employing arylboronic acids in the presence of Cu(II)

9-Arylpurines are efficiently formed with complete regioselectivity when purines are treated with arylboronic acids in the presence of copper(II) acetate. A variety of substituents on both coupling partners are well tolerated.

Cytotoxic and Antibacterial Activity of 2-Oxopurine Derivatives

Initial screening of the cytotoxic and antibacterial properties of 6-substituted 2-oxopurines and dihydro-2-oxopurines revealed that several compounds exhibited cytotoxicity against K-562 cells in the same range as the well known antileukemic drug 6-mercaptopurine. Most compounds were also tested for inhibitory effect on a Gram-positive bacterium, Lactobacillus casei, as well as the mycobacterium Mycobacterium tuberculosis. Generally the 2-oxopurines exhibited low antibacterial effect.

6-Chloropurines and organostannanes in palladium catalyzed cross coupling reactions

Abstract Carbon-carbon bond formation in the purine 6-position can easily be accomplished by palladium catalyzed cross coupling between 6-chloropurines and organostannanes without protection of the purine ring NH function. This technique provides a convenient route to potent cytokinines.

Antioxidant activity of synthetic cytokinin analogues: 6-alkynyl- and 6-alkenylpurines as novel 15-Lipoxygenase inhibitors.

Synthetic cytokinin analogues as well as the well known CKs 6-benzylaminopurine (BAP), kinetin and trans-zeatin were examined for antioxidant activity. The compounds were tested as potential diphenylpicrylhydrazyl (DPPH) scavengers and as inhibitors of 15-lipoxygenase (15-LO). The natural plant hormones were essentially inactive in both assays, but several synthetic analogues have a profound inhibiting effect on 15-lipoxygenase from soybeans. The same compounds were only weak DPPH scavengers and they may therefore be regarded as so-called non antioxidant inhibitors of 15-LO.

Screening of agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral leishmaniasis and Chagas disease.

There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC50 <0.5 μg/mL) while two others displayed IC50 <1 μg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasis and for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases.