ABSTRACT
[This corrects the article DOI: 10.1039/C7MD00445A.].
ABSTRACT
Here we describe the potency of 21 pentamidine analogues against the fungal pathogen, Pneumocystis carinii, in an ATP bioluminescent assay with toxicity profiles in 2 mammalian cell lines. Reduction of two 5-methyl-1,2,4-oxadiazole rings was applied to the synthesis of acid-labile bisamidines. Anti-Pneumocystis activity is discussed in the context of 3 groups of compounds depending on the main structural changes of the pentamidine lead structure. The groups include: 1) 1,4-bis(methylene)piperazine derivatives 1-5; 2) alkanediamide derivatives 6-10; 3) alkane-derived bisbenzamidines 11-21. IC50 values of 18 compounds were lower than the IC50 of pentamidine. Four bisamidines were active at nanogram concentrations. Introduction of sulfur atoms in the alkane bridge, replacement of the amidino groups with imidazoline rings, or attachment of nitro or amino groups to the benzene rings is responsible for remarkable activity of the new leading structures. The vast majority of compounds, including four highly active ones, can be classified as mild or nontoxic to host cells. These compounds show promise as candidates for new anti-Pneumocystis agents.
ABSTRACT
The effects of a new fibric acid derivative--beclobrate (Turec, Zyma) on serum lipid and apoprotein concentrations in 63 patients with primary hyperlipoproteinemia were examined. Beclobrate was given in the evening, 100 mg, once daily. After 3 months of beclobrate treatment mean total cholesterol concentration in serum decreased from 9.35 to 7.73 mmol/l (17.3%), mean LDL-cholesterol concentration from 6.32 to 5.38 mmol/l (14.9%), mean HDL-cholesterol concentration increased by 0.21 mmol/l (15.3% of initial value). The greatest decrease was observed in triglyceride concentration--by 50% of the initial value. Apoprotein B concentration decreased by 19.7%, apoprotein A1 and A2 concentration increased by 20.3% and 26.8% respectively. Higher initial values of total cholesterol and triglyceride concentration in serum were associated with greater concentration decrease after beclobrate treatment.
Subject(s)
Apoproteins/blood , Benzhydryl Compounds/therapeutic use , Hypercholesterolemia/drug therapy , Hypertriglyceridemia/drug therapy , Hypolipidemic Agents/therapeutic use , Lipids/blood , Adolescent , Adult , Aged , Humans , Middle AgedABSTRACT
After three months of beclobrate treatment (100 mg once daily) of 63 patients with primary hyperlipoproteinemia (HLP) significant decrease of total cholesterol concentration was found in type IIa by 12.9%, IIb by 23.7%, IV by 20.8%. LDL cholesterol concentration decreased in type IIa by 15.4%, IIb by 8.3%, in type IV non significant increase of LDL cholesterol by 21.6% was observed. Decrease of initial triglyceride level in type IIa by 36.1%, IIb by 41.2%, in type IV by 56.6% was found. HDL-cholesterol concentration increased in all examined HLP types in IIa by 19.5%, IIb by 19.3%, IV by 14.5%. Also initial apolipoprotein A1 and A2 levels increased in all HLP types examined, namely in type IIa respectively by 21.2% and 12.4%, IIb by 25.1% and 11.0%, in type IV by 23.6% and 34.9%. Serum apolipoprotein B concentration decreased significantly in type IIa by 20.5%, IIb by 28.4%, however in type IV a slight increase of apoprotein B level was observed. Comparison of HLP types response to beclobrate treatment revealed that the HLP types examined are significantly different in change size of LDL cholesterol concentration, triglyceride concentration and apoprotein B concentration after treatment.
