New potential renin inhibitors with dipeptide replacements in the molecule.

A series of eight non-peptidic potential renin inhibitors have been designed and synthesized. All of them contain dipeptide replacement: (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) in their molecules. Four among them comprise two additional analogs of dipeptide: (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta).

[DNA microarrays--perspective of application for drug effectivity and safety evaluation].

Microarray technology provides a unique tool for the determination of gene expression at the level of messenger RNA (mRNA). Microarray has been successfully applied to the high throughput simultaneous expression of many thousands of genes in a single experiment. One important application of DNA microarray technology, within the context of drugs effectiveness and safety evaluation studies, is its use as a screening tool for the identification of biochemical pathways, potential targets for novel molecular therapeutics, for the identification of molecular mechanisms of toxicity and to understand and predict individual drug sensitivity and resistance.

Topoisomerase II alpha expression and cytotoxicity of anthracyclines in human neoplastic cells.

Topoisomerase II is ATP dependent enzyme that catalyzes DNA strand passage, the pivotal process in replication, transcription, recombination etc. As part of this breakage and religation process the intermediate generated is a cleavable complex between DNA and topoisomerase II. This complex is the target for topoisomerase II inhibitors like epipodophyllotoxins, actinomycin D or anthracyclines.

New renin inhibitors containing pseudodipeptidic units in P3-P2 and P1-P1' positions.

A series of four non-peptidic renin inhibitors have been designed and synthesized. All of them contain in their molecule (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA), a hydrophobic portion at the C-terminus and a second dipeptide-like transition state analog or unnatural dipeptidic fragment at the N-terminus. Inhibitory activity of the compounds was measured in vitro by high performance liquid chromatography (HPLC).

The separation of EPO from other proteins in medical products formulated with different stabilizers.

The RP-HPLC method, useful for the separation of a protein of the erythropoietin formulations with different stabilizers, was elaborated. Using this method, rhEPO, HSA and other proteins, can be determined, depending on the sample composition. The method is sensitive and rapid.

Determination of in vitro activity renin inhibitors by HPLC method.

A high-performance liquid chromatographic assay has been developed to the separation of angiotensin I, tetradecapeptide and the tetrapeptide Leu-Val-Tyr-Ser. This purpose is achieved in a single step, using HPLC technique in the reversed phase system. The method is based on enzymatic hydrolysis of a substrate renin (TDP) with formation of angiotensin I (DP).

Application of the HPLC method for benzalkonium chloride determination in aerosol preparations.

Benzalkonium chloride (BAC) is a bacteriostatic agent used in the pharmaceutical industry as a preservative. BAC is a mixture of alkylbenzyldimethylammonium chlorides, the three most important of which being those with alkyl substituents C12, C14, C16 at the quaternary ammonium salt. The purpose of this study was to develop a method for determining benzalkonium chloride identity and content in aerosol preparations in which protein or steroid hormones are the active components.