ABSTRACT
Escin, a complex mixture of pentacyclic triterpene saponins obtained from horse chestnut seeds extract (HCSE; Aesculus hippocastanum L.), constitutes a traditional herbal active substance of preparations (drugs) used for a treatment of chronic venous insufficiency and capillary blood vessel leakage. A new approach to exploitation of pharmacological potential of this saponin complex has been recently proposed, in which the ß-escin mixture is perceived as a source of a hitherto unavailable raw material, pentacyclic triterpene aglycone-protoescigenin. Although many liquid chromatography methods are described in the literature for saponins determination, analysis of protoescigenin is barely mentioned. In this work, a new ultra-high performance liquid chromatography (UHPLC) method developed for protoescigenin quantification has been described. CAD (charged aerosol detection), as a relatively new detection method based on aerosol charging, has been applied in this method as an alternative to ultraviolet (UV) detection. The influence of individual parameters on CAD response and sensitivity was studied. The detection was performed using CAD and UV (200 nm) simultaneously and the results were compared with reference to linearity, accuracy, precision and limit of detection.
Subject(s)
Chromatography, High Pressure Liquid/methods , Escin/chemistry , Pentacyclic Triterpenes/isolation & purification , Aerosols , Aesculus/chemistry , Chromatography, High Pressure Liquid/instrumentation , Limit of Detection , Molecular Structure , Pentacyclic Triterpenes/chemistry , Reproducibility of Results , Spectrophotometry, UltravioletABSTRACT
A two-step chemical process for controlled degradation of escin, affording a mixture of olean-12-ene sapogenins, was elaborated and scaled up. The main component of the mixture--protoescigenin--was isolated and purified, in the form of its corresponding monohydrate, without resource to chromatographic methods. This material was further converted into the high purity 3,24;16,22-di-O,O-isopropylidene derivative in a validated large scale laboratory process.
Subject(s)
Escin/chemistry , Escin/isolation & purification , Crystallography, X-Ray , Sapogenins/chemistry , Sapogenins/isolation & purificationABSTRACT
A series of novel 6H-indolo[2,3-b]quinoline derivatives, substituted at C-2, C-9 or N-6 position with dialkyl(alkylamino)alkyl chains differing in the number of methylene groups, was prepared. These compounds were evaluated in vitro for their antimicrobial and cytotoxic activity against several cell lines of different origin and tested for their ability to influence the cell cycle and inhibit topoisomerase II activity. Liphophilic and calf thymus DNA-binding properties of these compounds were also investigated. All the compounds tested inhibited the growth of Gram-positive bacteria and fungi at MIC values ranging between 0.25 and 1 mM. They also showed cytotoxic activity against KB (human cervix carcinoma) cells (ID50 varied from 2.1 to 9.0 microM) and were able to overcome multidrug resistance in colorectal adenocarcinoma LoVo/DX, uterine sarcoma MES-SA/DX5 and promyelocytic leukemia HL-60/MX2 cells (the values of the resistance index RI fell between 0.54 and 2.4). The compounds induced G2M-phase cell cycle arrest in Jurkat T-cell leukemia cells, revealed DNA-binding properties and inhibited topoisomerase II activity.
Subject(s)
Indoles/pharmacology , Quinolines/pharmacology , Topoisomerase II Inhibitors , Alkaloids/chemical synthesis , Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , DNA/drug effects , DNA/metabolism , DNA Adducts/metabolism , Drug Screening Assays, Antitumor , Humans , Indoles/chemical synthesis , Indoles/chemistry , KB Cells , Microbial Sensitivity Tests , Quinolines/chemical synthesis , Quinolines/chemistryABSTRACT
A systematic investigation into the impact of the substituents introduced into the indolo[2,3-b]quinoline system is described. The findings clearly demonstrate that the compounds bearing a methyl group or a longer aliphatic chain at the N-6 position are inactive against prokaryotic and eukaryotic cells. The introduction of alkyl-amino-alkyl substituent at the N-6 position of indolo[2,3-b]quinoline accounts for the appearance of the antimicrobial and.cytotoxic properties. The cytotoxicity against oral epidermoid carcinoma KB (ID50) is in the range from 2.0 to 9.0 microM, and the antimicrobial activity (MIC) falls between 0.03 and 0.50 mM. The structural relation within 6H-indolo[2,3-b]quinolines, concerning their antimicrobial and cytotoxic activity, corresponds well with their ability to bind DNA and to inhibit topoisomerase II activity.
