Potential Cytostatics Research Articles

Potential anti-cancer drugs commonly used for other indications.

An increasing resistance of mammalian tumor cells to chemotherapy along with the severe side effects of commonly used cytostatics has raised the urgency in the search for new anti-cancer agents. Several drugs originally approved for indications other than cancer treatment have recently been found to have a cytostatic effect on cancer cells. These drugs could be expediently repurposed as anti-cancer agents, since they have already been tested for toxicity in humans and animals. The groups of newly recognized potential cytostatics discussed in this review include benzimidazole anthelmintics (albendazole, mebendazole, flubendazole), anti-hypertensive drugs (doxazosin, propranolol), psychopharmaceuticals (chlorpromazine, clomipramine) and antidiabetic drugs (metformin, pioglitazone). All these drugs have a definite potential to be used especially in combinations with other cytostatics; the chemotherapy targeting of multiple sites now represents a promising approach in cancer treatment. The present review summarizes recent information about the anti-cancer effects of selected drugs commonly used for other medical indications. Our aim is not to collect all the reported results, but to present an overview of various possibilities. Advantages, disadvantages and further perspectives regarding individual drugs are discussed and evaluated.

Pt(II) and Pt(IV) complexes with large hydrophobic ligands: a study of new potential cytostatics

Breast cancer is a major health problem among women in the world. The successful treatment of this disease is limited by the fact that essentially all breast cancers become resistant to chemotherapy. Therefore, there is a need to design new chemotherapeutic agents able not only to target breast cancer but also to display increased efficacy and overall decreased systemic toxicity. Platinum (II) complexes are widely used in cancer chemotherapy. The most important platinum-based drugs are cisplatin, carboplatin, the first platinum (II) derivatives entering the market, and more recently oxaliplatin, nedaplatin, iobaplatin, heptaplatin and picoplatin The computer-aided calculations are commonly applied to rational design of many pharmacological group of drugs. Platinum based cytostatics are one of the exceptions. The correlation between antiproliferative activity and molecular descriptors of Pt-drug analogues of clinically used complexes are present in this work. The main goal of this study was to show the relations between hydrophobicity and biological activity in the series of neutral platinum (II) and platinum(IV) complexes. The object of the study is several groups of analogues of oxaliplatin and picoplatin complexes, with N-donors ligands (amidines, adamantines and memantines). The influence of the type and the positions of the substituents on the conformational energies and thermodynamic stabilities of a series of platinum (II) and platinum (IV) complexes has been studied by molecular mechanics. The calculations were carried out for the ligand conformations. The obtained energies and thermodynamic stabilities are in agreement with experimental data on the reactivity and antitumor activity of the compounds.

General route to the total synthesis of sempervirine analogues containing modified E rings, potential cytostatics

Sempervirine analogues 13a– c with different E rings have been obtained via inverse electron demand Diels–Alder reactions of 5-acetyl-3-(methylsulfanyl)-1,2,4-triazine with cyclic enamines (formation of D and E rings) followed by Fischer indole synthesis under microwave irradiation on solid support (formation of A and B rings) and subsequent annulation of indole derivatives 10a– c via a directed metallation route (formation of C rings).

Use of rat hepatocytes immobilized in agarose gel threads for biosynthesis of metabolites of potential cytostatics

The aim of this work was to evaluate possibility of use of the rat isolated hepatocytes immobilized in agarose gel and continuously perfused for production of needed metabolites of two potential cytostatics, benfluron (5-(2-dimethylamino-ethoxy)-7-oxo-7H-benzo[c]fluorene) and oracin (6-[2-(hydroxyethyl) amino-ethyl]-5,11-dioxo-5,6-dihydro-11H-indeno [1,2-c]isoquinoline). The rat isolated hepatocytes obtained by two-step collagenase perfusion method were immobilized in agarose threads and perfused in a small bioreactor under a recirculation regimes. Biosynthesis of 9-hydroxybenfluron and 3-hydroxyoracin in immobilized rat hepatocytes was studied. Yields of the metabolites of interest in hepatocytes in immobilized and perfused rat hepatocytes was compared to production of metabolites in hepatocyte suspension and in rats in vivo. 9-hydroxybenfluron was presented during perfusion of immobilized rat hepatocytes in a relatively high amounts but total recovery all forms of benfluron was very low due to especially high binding to components of the perfusion system. More effective method remains the production of 9-hydroxybenfluron in rats in vivo. A considerable biosynthesis of 3-hydroxyoracin by immobilized rat hepatocytes in the bioreactor was found. Concentration of the metabolite in the perfusate rose continuously during 6 hours of perfusion. 3-hydroxyoracin production was increased several times with use of immobilized hepatocytes from rats treated for three days with methylcholanthrene. The yield of 3-hydroxyoracin in rats in vivo was comparably high but an advantage of in vitro synthesis is a much shorter interval to obtain the same amount of the metabolite of interest. In spite of some limitations in compounds exerting high trapping in the perfusion system, the method of the immobilized and perfused hepatocytes can be very useful and effective for production of some drug metabolites in biochemistry and pharmacology.

N-phosphorylated amino acids as potential cytostatics

Phosphoramidic dichlorides 3 are synthesized by nucleophilic attack of methyl 2-(1-ethylenimino)-alkanoates 1 on POCl3 or by the reaction of amino acid methyl ester hydrochlorides 2 with POCl3. Subsequent treatment of 3 with ethylenimine affords the TEPA-analogs 4, and with 3-(1-ethylenimino)-1-propanol (6) the IFOSFAMID analogous 1,3,2-oxaza-phosphorines 5, the cytostatic activity of which was tested in the P388-leukemia of the CD2F1-mouse.

ChemInform Abstract: Synthesis of 2,7‐Fluorenone Bisglycidyl Ether and Related Compounds as Potential Cytostatics.

ChemInformVolume 21, Issue 35 Isocyclic Compounds ChemInform Abstract: Synthesis of 2,7-Fluorenone Bisglycidyl Ether and Related Compounds as Potential Cytostatics. J. MLOCHOWSKI, J. MLOCHOWSKI Inst. Org. Phys. Chem., Tech. Univ., PL-50-370 Wroclaw, Pol.Search for more papers by this authorJ. PALUS, J. PALUS Inst. Org. Phys. Chem., Tech. Univ., PL-50-370 Wroclaw, Pol.Search for more papers by this author J. MLOCHOWSKI, J. MLOCHOWSKI Inst. Org. Phys. Chem., Tech. Univ., PL-50-370 Wroclaw, Pol.Search for more papers by this authorJ. PALUS, J. PALUS Inst. Org. Phys. Chem., Tech. Univ., PL-50-370 Wroclaw, Pol.Search for more papers by this author First published: August 28, 1990 https://doi.org/10.1002/chin.199035144Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue35August 28, 1990 RelatedInformation

Synthesis of 2,7‐Fluorenone Bisglycidyl Ether and related compounds as potential cytostatics

AbstractThe syntheses of fluorenone derivatives having one to three glycidyl groups and related compounds are reported. Their activity against experimental tumors in vitro in relation to the molecular structure is discussed.

ChemInform Abstract: Synthesis of (3′,3′‐Dimethyloxiranyl)quinones and (Dimethylacetyl)quinones as Potential Cytostatics.

AbstractThe title quinones (I) show high cytotoxicity against KB cells in contrast to the significantly lower activity of the quinones (II), (III) and (IV).

Synthesis of (3′,3′‐Dimethyloxiranyl)quinones and (Dimethylacetyl)quinones as Potential Cytostatics

Abstract1,4‐Benzoquinones and 1,4‐naphthoquinones carrying 3′,3′‐dimethyloxiranyl, dimethylacetyl or oxiranylmethyloxy substituents (1, 2 or 3) have been synthesized. The methods presented involved epoxidation of a sterically overcrowded double bond as a crucial step for synthesis of (3′,3′‐dimethyloxiranyl)quinones 1. Reaction of aryllithium derivatives with 2‐chloro‐2‐methyl‐propanol unexpectedly led to (dimethyl)acetylarenes 11 subsequently oxidized to (dimethylacetyl)‐quinones 2. High cytotoxicity of 1 against KB cells has been revealed contrary to significantly lower activity of 2 and 3. The structure‐activity relationship was discussed in terms of current theory of biologically activated alkylating agents.