2-Acylamino-5-chlorobenzophenones with enhanced selectivity towards malaria parasites.

Previously we described a series of 5-acylaminobenzophenones with considerable antimalarial activity. Unfortunately, most compounds also displayed high cytotoxicity resulting in low selectivity towards malaria parasites. Through the replacement of the 5-acylamino moiety by simple chlorine and further modifications of the 2-acylamino residue we could obtain inhibitors with improved selectivity towards malaria parasites combined with an acceptable reduction of antimalarial activity.

Side chain azasteroids and thiasteroids as sterol methyltransferase inhibitors in ergosterol biosynthesis.

The synthesis of some novel azasteroids and thiasteroids based on a pregnan nucleus with a Delta7 double bond in two to five steps from the key aldehyde (3S,20S)-20-formylpregn-7-en-3-yl acetate has been disclosed herein. These compounds were evaluated as potential inhibitors of the enzyme Delta24-sterol methyltransferase (24-SMT), which is a key enzyme in the biosynthesis of ergosterol, and for their effects on the growth of the yeast Yarrowia lipolytica. Most of the side chain modified analogues were recognized as 24-SMT inhibitors, and in particular the 23-azasteroids 5f-5i and the 24-azasteroid 11 showed potent antifungal activity.

Antimalarial and antitrypanosomal activity of a series of amide and sulfonamide derivatives of a 2,5-diaminobenzophenone.

Here, we describe a series of readily obtainable benzophenone derivatives with antimalarial and antitrypanosomal activity. The most active compounds display submicromolar activity against Plasmodium falciparum. Micromolar activity is obtained against Trypanosoma brucei.

Structure-based optimization of aldose reductase inhibitors originating from virtual screening.

Diabetes mellitus is a universal health problem. The World Health Organization (WHO) estimates that 150 million people suffer from diabetes mellitus worldwide in 2005. Long-term complications are a serious problem in the treatment of diabetes, manifesting in macrovascular and microvascular complications.

Studies addressing the importance of charge in the binding of fosmidomycin-like molecules to deoxyxylulosephosphate reductoisomerase.

Fosmidomycin and its homologue FR900098 are inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase, which is part of the mevalonate-independent isoprenoid biosynthetic pathway. Replacement of the phosphonate moiety by uncharged sulfone or sulfonamide partial structures resulted in complete loss of activity. Dropping one of the two negative charges resulted in a marked decrease in activity.

Alkynyl ruthenium colorimetric sensors: optimizing the selectivity toward fluoride anion.

We report on the synthesis of alkynyl ruthenium colorimetric sensors whose receptors are constituted by thiazolidinedione, rhodanine, or barbituric heads as recognition centers for anions. As modifications in the charge density at these recognition centers affect the whole molecule, through the alkynyl ligand acting as a communicating wire, the effects of hydrogen-bonding interactions with the anions were observed with the naked eye and monitored by UV-vis absorption spectrometry. The selectivity of the sensors was improved through electronic modifications of the alkynyl ruthenium subunit: the higher the electron density at the receptor head, the higher the selectivity is.