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Kombretastatyna A-4 (CA-4) i jej analogi : synteza i aktywność biologiczna

Dzierzbicka K., Kubacka P., Renusz S., Kołodziejczyk A.M.

Wiadomości Chemiczne

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2008

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[Z] 62, 11-12

1037-1064

EN

This article described synthesis and biological activity of combretastatin A-4 (CA-4) and its analogues. Combretastatin A-4 (CA-4), a natural product isolated from the South African bush willow tree Combretum caffrum, binds to the colchicine binding site and inhibits the polymerization of microtubules. CA-4 exhibits potent cytotoxicity against a variety of human cancer cell lines including multidrug-resistant (MDR) cell lines [5-7]. The studies of structure-activity relationship (SAR) of CA-4 1 (Fig. 1) showed that 3,4,5-trimethoxy substitution on the A ring and the 4'-methoxy group on the B ring and the cis-olefin configuration are crucial for potent cytotoxicity, while the 3'-hydroxy group is optional [5-7]. A many of CA-4 analogues were synthesized where the double bond have been replaced by introduction of nonheterocyclic groups (e.g. ethers, olefins, ketones, sulfonates, sulfonamides, amide derivatives, amine, cyclopentanes) or heterocyclic groups containing five-membered rings (e.g. pyrazoles, thiazoles, triazoles, tetrazoles, oxazoles, furans, dioxolanes, thiophenes) and indoles [5, 7, 41, 56] (Fig. 9-12). Up to now, many CA-4 analogues and their biological activity have been extensively studied and three derivatives are currently in clinical trials: a water-soluble disodium phosphate derivative of CA-4 (CA-4P) 11c (Fig. 3); Oxi-4503, a water-soluble combretastatin A-1 (CA-1diP) 4a (Fig. 1); and AC7700 59e (Scheme 7) an aminocombretastatin prodrug developed in Japan in 1998 [5-10, 34].

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Inhibitory mikrotubul w terapii przeciwnowotworowej

Dzierzbicka K., Kołodziejczyk A.M.

Wiadomości Chemiczne

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2006

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[Z] 60, 5-6

345-364

EN

Microtubule targeting drugs being in the late preclinical or early clinical development are described in this article. New semisynthetic paclitaxel analogues, natural compounds of diverse structure such as epothilones, combretastatins, colchino-ids or dolastatins and synthetic compounds of low molecular weight such as heterocombretastatins, sulfonamides, phenstatins, indoles and quinolones belong to this category of anticancer medicines. Microtubules are hollow tubes consisting of L- and B-tubulin heterodimer proteins that polymerize parallelly to a cylindrical axis. The targeting of microtubules is an important mechanism in cancer chemotherapy for such drugs as the vinca alkaloids (vincristine (1), vin-blastine (la)), podophilotoxin, their semisynthetic analogues and taxanes (paclitaxel (2), docetaxel (3)) known of their great usefulness in the anticancer therapy. These agents may stabilize microtubules, as the taxanes do, or destabilize them, as it is in the case of the vinca alkaloids. Today, more than 30 compounds targeting tubulin, either stabilizing or destabilizing microtubule dynamics, are in late preclinical or early clinical development. Despite of more than 30 years after the discovery of paclitaxel microtubule inhibitors they are still of the topic of interest of all over the world. In the end of 1990 and up to 2005 year survey articles on the microtubule inhibitors were published .We expect now that the paper which presents last results study may be useful.

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Solvent micro-extraction of polycyclic aromatic hydrocarbons from mineral oils

Ślebioda M., Kot A., Kołodziejczyk A. M.

Chemia Analityczna

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1998

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Vol. 43, No. 5

867-872

EN

A method of determination of polycyclic aromatic hydrocarbons in mineral oil samples by simple solvent micro-extraction and high performance liquid chromatography is described. Distribution of polycyclic aromatic hydrocarbons and other hydrocarbons between dimethyl sulphoxide and cyclohexane solvent was exploited for the enrichment of compounds from oil matrix. Reversed-phase liquid chromatography with coupled fluorescence detection was applied to separate and determine these polycyclic aromatic hydrocarbons. Various factors which may affect the recovery of polycyclic aromatic hydrocarbons from oil, including ratio of solvents used for the solvent extraction, maximum sample load, are discussed. This simplified method of determination polycyclic aromatic hydrocarbons in mineral oils has been applied for the products of one of Polish petroleum refineries.

PL

Przedstawiono metodę oznaczania wielopierścieniowych węglowodorów aromatycznych w olejach mineralnych. Metoda izolacji tych węglowodorów z matrycy olejowej polega na ekstrakcji próbki mieszaniną dimetylosulfotlenku i cykloheksanu. Do oznaczeń końcowych wykorzystano wysokosprawną chromatografię cieczową z detekcją fluorescencyjną. Zbadano kilka czynników mogących mieć wpływ na odzysk wielopierścieniowych węglowodorów aromatycznych z oleju, między innymi stosunek objętościowy zastosowanej mieszaniny rozpuszczalników, jak i wpływ obciążenia próbki na sprawność ekstrakcji. Proponowana prosta metoda oznaczania wielopierścieniowych węglowodorów aromatycznych w matrycach olejowych została zastosowana do oznaczeń tych związków w próbkach olejów produkowanych przez jeden z polskich zakładów rafineryjnych.