Contemporary radiopharmacy has played a significant role in the development of early oncological diagnostics. Such radiopharmaceutics as 18F-FMISO, 123I-IAZA, 99m Tc-HL-91 (Fig. 1b, 3b, 7b) are used in the state-of-the art scintigraphic and tomographic techniques, i.e. in the PET and SPECT methods to determine carcinoma progression and detect cells in hipoxic state already at the early stage of carcinoma development [2, 3]. These noninvasive and selective for hipoxic cells methods are characterized by excellent sensitivity and do not exert noxious effect on the remaining cells of the human organism [4, 5]. Characteristic hipoxia of solid tumors can be also identified with invasive methods, e.g. Elisa test or measurement of oxygen concentration in pathological cells using a microprobe. However, medical interference in the tissues affects the condition of the whole organism. Technical complications and low accuracy resulting from non-uniform hipoxia of the cancerous tissue environment render rear usage of these methods in clinical practice [3]. Diagnosis of hipoxia occurring in the carcinoma-changed cells permits treatment with drugs possessing bioreductive mechanism of activity. In this group of drugs, apart from nitro compounds and chinon derivatives, we can distinguish compounds with N-oxide structure [25]. Tripazamine (Fig. 11b) and banoxantrone (Fig. 11a) represent the latter group of compounds. These are so far the drugs with the best therapeutic parameters expressed by selectivity, efficiency of action and low general toxicity [25]. Also, gene therapy with the use of adenovirus vector coding nitroreductase seems to be a promising mode of treatment. This enzyme induces cytotoxic activity of nitro compounds, e.g. CB1954 (Fig. 10c), for cancerous cells with hypoxia [26].
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Cancer chemotherapy over twenty years has been under extremely intensive investigation. Failure in the treatment of neoplasms is due to characteristic fe-atures of cancer cells. Their structure delays and decreases the efficacy of drugs administered orally or intravenously. Therefore, greater emphasis is placed on the development of new molecular studies. The development of particular molecular diagnostic methods is based on new advances in immunology, genetics and nuclear medicine. Nuclear medicine concentrates on the diagnostics and treatment of various diseases, including neoplasms treated by means of radiopharmaceuticals. The isotope most commonly used as a source of g radiation for radiopharma-ceuticals is technetium (99mTc). The complexes of this radiotracer (e.g. 99mTc-HM-PAO, 99mTc-CB-PAO, 99mTc-ECD) are widely used for brain imaging. These compounds indicate areas of normal blood supply in the brain, but do not enter hypoxic tumour cells. The differences in oxygenation level between normal and cancer cells is key strategy used not only in the diagnostics, but also in the treatment of neoplasms. Some compounds [quinone antibiotics,nitroimidazoles, tirapazamine] are known as hypoxia selective agents activated in low oxygen concentrations. Another strategy used in anticancer therapy aims at the inhibition of angiogenesis in the tumour; other methods limit the growth of tumour - these include use of inhibitory enzymes such as telomerase inhibitors (phosphorothioate oligonucleotides, cisplatin) and polyamine metabolism inhibitors (DFMO, MGBG). Valuable antineoplastic drugs originate from natural sources. Currently, the derivatives of acronycine and spongiostatin are being investigated. Natural compounds with a documented anticancer activity include, for example, taxol , etopozide and tenipozide. New directions in the research of new compounds for use in the diagnostics and treatment of neoplastic diseases are closely related to the development of molecular studies, which offer explanation of complex patophysiology of tumours on molecular level. Also. medical chemistry plays an important role in modern investigation methods, such as molecular modelling.
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The RP HPLC method for the determination of ethylene dicysteine di-ethylester (BCD) is presented. The separation was achieved on RP C(18) column with methanol-water as isocratic mobile phase, and by use of photometric UV detection. This method was applied for the determination of ECD purity and stability in phosphate buffers pH 5.5 and 6.0.
PL
Przedstawiono metodę oznaczania estru dietylowego etylenodicysteiny (ECD) metodą HPLC. Oznaczanie przeprowadzono na kolumnie RP C18, fazę ruchomą stanowiła mieszanina metanolu i wody. Używano detektora fotometrycznego UV. Metodę wykorzystano do badania czystości ECD oraz trwałości w buforze fosforanowym o pH 5.5 i 6.0.
A series of new benzimidazole derivatives were synthesized and tested in vitro for possible anticancer activity. Their effect of proliferation into selected tumor cell lines at normoxia and hypoxia conditions was determined by WST-1 test. Additionally, apoptosis test (caspase 3/7 assay) was used to check the mode caused by the agents of cell death. Four of the examined compounds (7, 8, 13, 11) showed a very good antiproliferative effect and three of them were specific for hypoxia conditions (8, 14, 11). Compound 8 was the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/ normoxia cytotoxic coefficient of compound 14 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) - a reference compound in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Screening test of caspase-dependent apoptosis proved that exposure to A549 cells of compounds 7-8 and 13-14 for 48 h promote apoptotic cell death. These results supplement our earlier study of the activity of new potentialy cytotoxic heterocyclic compounds against selected tumor cells.
Nanotechnologia jest szybko rozwijającą się multidyscyplinarną dziedziną nauki obejmującą jednocześnie przemysł i medycynę oraz obszary pośrednio i bezpośrednio z nimi związane. Nanotechnologia znalazła także zastosowanie w farmacji między innymi w badaniach nad drogą podania leku, w nowych postaciach leku czy samej strukturze chemicznej substancji aktywnej prowadzącej do uzyskania leku o obniżonej toksyczności. Technika ta jest między innymi innowacyjną metodą biodystrybucji, np. w badaniach nad cząsteczkami leków dostarczanymi do określonego celu biologicznego. Z drugiej strony nanotechnologię możemy zastosować w diagnostyce i terapii oraz w monitorowaniu i kontroli wszystkich układów biologicznych. Nanocząsteczki w postaci polimerów, kompleksów metali, liposomów, micelli, dendrymerów, mikrokapsułek oraz lipoprotein odgrywają znaczącą rolę w diagnostyce i terapii wielu chorób.
This report describes the effect of triacontanol on shoot multiplication and production of antioxidant compounds (carnosic acid, carnosol and rosmarinic acid) in S. officinalis cultures grown on MS basal medium (agar solidified medium supplemented with 0.1 mg l-1 IAA, 0.45 mg l-1 BAP). It was found that shoot proliferation significantly increased when triacontanol at concentrations of 5, 10 or 20 µg l-1 was added to the medium. HPLC analysis of acetone and methanolic extracts of sage shoots showed that the production of diterpenoids, carnosic acid/carnosol ratio, as well as, contents of rosmarinic acid were also affected by the treatment with triacontanol. The highest stimulation effect of triacontanol was observed on the production of carnosol, where the treatment with 20 µg l l-1 increased the content of this diterpenoid 4.5-fold compared to that in the control (sage shoots growing on MS basal medium, only).
The concentrations of carnosic acid, carnosol and rosmarinic acid in different materials from differentiated (multiple shoot cultures and regenerated plants) and undifferentiated (callus and cell suspension) in vitro cultures of Salvia officinalis were determined by HPLC. The results suggested that diterpenoid (carnosic acid and carnosol) production is closely related to shoot differentiation. The highest diterpenoid yield (11.4 mg g-1 for carnosic acid and 1.1 mg g-1 for carnosol) was achieved in shoots of 10-week-old micropropagated plants. The levels were comparable to those found in shoots of naturally growing plants. Undifferentiated callus and cell suspension cultures produced only very low amounts of carnosol (ca. 0.05 mg g-1 of dry weight). In contrast, content of rosmarinic acid in callus and suspension cultures as well as shoots growing in vitro and in vivo was similar and ranged between 11.2 and 18.6 mg g-1 of dry weight.
Obtained benzimidazole derivatives, our next synthesized heterocyclic compounds, belong to a new group of chemical bondings with potential anticancer properties (Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2006, J Liguid Chrom Rel Tech 29: 2367-2385; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2008, Wiad Chem 62: 11-12, in Polish; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2011, J Liguid Chrom Rel Tech 34: 1901-1912). We used HPLC analysis to determine stability of these compounds in 0.2% DMSO (dimethyl sulfoxide). Optimisation of the chromatographic system and validation of the established analytical method were performed. Reversed phases (RP-18) and a 1:1 mixture of acetate buffer (pH 4.5) and acetonitrile as a mobile phase were used for all the analysed compounds at a flow rate 1.0 mL/min. The eluted compounds were monitored using a UV detector, the wavelength was specific for compounds 6 and 9 and compounds 7 and 10. The retention time was specific for all four compounds. The used method was found to have linearity in the concentration range of (0.1 mg/mL-0.1 μg/mL) with a correlation coefficient not less than r2=0.9995. Statistical validation of the method proved it to be a simple, highly precise and accurate way to determine the stability of benzimidazole derivatives in 0.2% DMSO. The recoveries of all four compounds examined were in the range 99.24-100.00%. The developed HPLC analysis revealed that the compounds studied remain homogeneous in 0.2% DMSO for up to 96 h and that the analysed N-oxide benzimidazole derivatives do not disintegrate into their analogues - benzimidazole derivatives. Compounds 8, 6 and 9 exhibit the best cytotoxic properties under normoxic conditions when tested against cells of human malignant melanoma WM 115.
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