Chemical antagonism between photodynamic agents and chemotherapeutics: mechanism and avoidance.

We report a photochemical reaction-induced antagonism between the photodynamic agent (PS) and anti-cancer drugs during combined therapy. The annihilation of singlet oxygen and alkene-containing drugs into inactive drug hydroperoxides is responsible for the antagonism, and results in decreased efficacy against several cancer cell lines. Experimental and simulation results reveal that the annihilation abates with increasing distance between the PS and drugs via confining the PS and drugs into separated vehicles. As a result, antagonism can be switched to synergism in treating both drug sensitive and resistant cancer cells.

Biomimetic synthesis: discovery of xanthanolide dimers.

Starting from xanthatin, the biomimetic synthesis of 4ß,5ß-epoxyxanthatin-1α,4α-endoperoxide, a novel monomeric xanthanolide, has been achieved. Moreover, four unprecedented xanthanolide dimers were synthesized by three different dimerizations of xanthatin, either in a head-to-head or head-to-tail fashion. Notably, these dimeric compounds were firstly identified as artifacts in the laboratory, and two of them, mogolides A and B, proved to be natural products present in the Xanthium mogolium Kitag plant.

The therapeutic potential of semi-synthetic artemisinin and synthetic endoperoxide antimalarial agents.

Artemisinin derivatives such as artesunate, dihydroartemisinin and artemether are playing an increasing role in the treatment of drug-resistant malaria. They are the most potent antimalarials available, rapidly killing all asexual stages of the parasite Plasmodium falciparum. This review highlights the recent developments in the area of improved second-generation semi-synthetic artemisinin derivatives and fully synthetic antimalarial endoperoxide drugs. In pursuit of synthetic analogues of the artemisinins, one of the major challenges for chemists in this area has been the non-trivial development of techniques for the introduction of the peroxide bridge into candidate drugs. Although chemical research has enabled chemists to incorporate the endoperoxide 'warhead' into synthetic analogues of artemisinin, significant drawbacks with many candidates have included comparatively poor antimalarial activity, non-stereoselective syntheses and chemical approaches that are not readily amenable to scale up. However, very recent progress with synthetic 1,2,4-trioxolanes provides a new benchmark for future medicinal chemistry efforts in this area.

Effects of droplet size on the oxidative stability of oil-in-water emulsions.

The effects of droplet size and emulsifiers on oxidative stability of polyunsaturated TAG in oil-in-water (o/w) emulsions with droplet sizes of 0.806 +/- 0.0690, 3.28 +/- 0.0660, or 10.7 +/- 0.106 microm (mean +/- SD) were investigated. Hydroperoxide contents in the emulsion with a mean droplet size of 0.831 microm were significantly lower than those in the emulsion with a mean droplet size of 12.8 microm for up to 120 h of oxidation time. Residual oxygen contents in the headspace air of the vials containing an o/w emulsion with a mean droplet size of 0.831 microm were lower compared with those of the emulsion with a mean droplet size of 12.8 microm. Hexanal developed from soybean oil TAG o/w emulsions with smaller droplet size showed significantly lower residual oxygen contents than those of the larger droplet size emulsions. Consequently, oxidative stability of TAG in o/w emulsions could be controlled by the size of oil droplet even though the origins of TAG were different. Spin-spin relaxation time of protons of acyl residues on TAG in o/w emulsions measured by H NMR suggested that motional frequency of some acyl residues was shorter in o/w emulsions with a smaller droplet size. The effect of the wedge associated with hydrophobic acyl residues of emulsifiers was proposed as a possible mechanism to explain differences in oxidative stability between o/w emulsions with different droplet sizes.

New readily accessible peroxides with high anti-malarial potency.

In an explorative study for new anti-malarial substances using the methyl esters (1 and 2) of peroxyplakoric acids A(3) and B(3) as scaffolds, 6-carbomethoxymethyl-3-methoxy-3-pentyl-1,2-dioxane, which has been readily synthesized from 6-keto-alpha,beta-unsaturated ester, was found to exhibit potent anti-malarial activity with high selective toxicity.

Antimalarial t-butylperoxyamines.

Twelve t-butylperoxyamines (6-17) were synthesized as targeted antimalarials and evaluated for antimalarial activity in vivo against Plasmodium berghei in mice and in vitro against both chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum. Compound 8 was found to have highest potency with activity at 80 and 160mg/kg dose in vivo and compound 11 exhibited highest efficacy in vitro.

[Disinfectants based on peracid-splitting compounds (author's transl)]. / Desinfektionsmittel auf der Basis persäureabspaltender Verbindungen.

All organic peracids are capable of damaging enzymes of the microbial cell irreversibly by oxidation and can thus kill microbes. When using organic peracids as a disinfectant it is expedient to prepare them immediately prior to use. This is possible by employing mixtures in powder form of acid depots (anhydrides, amides, esters) and hydrogen peroxide depots which react together with water only at the time of preparing the solution to form a balanced system, the active complex proper, comprising organic peracid, organic acid, hydrogen peroxide and water.