[Signal pathways of cell proliferation and death as targets of potential chemotherapeutics]. / Signálne dráhy bunkovej proliferácie a smrti ako ciele potenciálnych chemoterapeutík.

The purpose of this paper is to review current information concerning signal transduction pathways of cell proliferation and cell death applicable in the research of antitumor compounds with a specific effect. Actually, cancer counts among the world gravest diseases. Research of the mechanisms of action of chemotherapeutics helps us to find compounds with high cytotoxic activity to tumor cells and low or no cytotoxicity to normal cells. Many present studies deal with the ability of drugs to hit the proliferation signal pathways or cell death pathways specifically. Various proliferation signal pathways have been identified, e.g. pathways of mitogen-activated proteinkinases. In original studies, cell death was considered to perform in necrotic and apoptotic forms, whereas in contrast to necrosis, apoptosis represented the programmed process. However, other forms of programmed cell death were discovered, the programmed necrosis and autophagic cell death. Similarly, beside the intrinsic, mitochondrial-mediated, and extrinsic, receptor-mediated pathways, new mechanisms of induction of apoptosis were discovered: the endoplasmic reticulum stress pathway in which calcium plays an important role, the lysosomal pathway and the ceramide-induced pathway. Current information concerning transduction of antiproliferative and death stimuli in cells allows to explain the mechanisms of action of known drugs and also brings novel therapeutical targets which can serve in treatment of such diseases as cancer.

[Cytotoxicity screening and mode of action of natural and synthetically prepared compounds usable in tumour chemotherapy]. / Skríning cytotoxicity in vitro a mechanizmus pôsobenia prírodných a synteticky pripravených látok vyuzitel'ných v chemoterapii nádorov.

The paper reviews the current approaches to cytotoxic effect screening and mode of action of natural and synthetic compounds usable in tumour chemotherapy. Oncological diseases belong to the most frequently occurring and the most serious diseases that threaten millions of human lives. A serious complication of anticancer therapy is an inadequate therapeutic answer which is caused by the resistance of the human organism to the employed drugs, chemotherapeutic agents. Therefore the resistance is one of the driving forces which constantly force us to search for new anticancer effective drugs of natural or synthetic origin. Primary screening in vitro, in which by different methods the sensitivity of cancer cells growing in vitro to cytotoxic compounds is monitored, is commonly and routinely used for searching for new potential cytostatics today. The properties of a potential anticancer compound are characterized by different parameters, which include antiproliferative activity, monitoring of structural and functional changes in the cytoplasmic membrane, changes in cell proteins and nucleic acids content, cell metabolism changes, cell cycle changes, induction of apoptosis, enzymatic activity (dihydrofolate reductase, proteinases, proteinkinases, topoisomerases, tymidylatsynthetase), effect on mitochondria, cell cytoskeleton, telomerase activity, etc. By monitoring these parameters, the mode of action of a cytotoxically effective compound can be followed up.

Simple and convenient preparation of 1-(arylamino)methylbenzotriazoles and -(arylamino)methylbenzimidazoles.

The preparation of 1-(arylamino)methylbenzotriazoles 1a-17a and benzimidazoles 1b-17b is described and their antibacterial activity evaluated. 1-Hydroxymethylbenzazo-les react with the appropriate aniline to yield the target compounds. These were characterized using 1H NMR, IR, UV spectra. The compounds displayed no significant antibacterial activity.

Dimethyl 2-[[2-(methoxycarbonyl)-1-(methoxycarbonylmethyl)pyrrol-4-yl]methylene]propanedioate.

The title compound, C(15)H(17)NO(8), is a pyrrole-ethene derivative with potential biological activity. Although a large part of the molecule is planar, there is no structural evidence for any conjugation push-pull effect across the ethylenic bond, which is usually observed for substituted ethylenes; pi-electron delocalization appears to be restricted to the 2-(methoxycarbonyl)pyrrole moiety.

[Chemical structure of quinolones and their antibacterial activity. II. 4-quinolones: their occurrence in nature and biological properties]. / Chemická struktúra chinolónov a ich antibakteriálna aktivita. II. 4-chinolóny--ich výskyt v prírode a biologické vlastnosti.

The review paper deals with the natural occurrence, biological properties, and uses of 4-quinolones concentrating on 3-substituted-4-quinolones and their antimicrobial activity.

Dimethyl (1-methyl-1,3-benzimidazol-5-yl)aminomethylenepropanedioate monohydrate.

In the title compound, C(14)H(15)N(3)O(4).H(2)O, there is a strong conjugation push-pull effect across the central double bond, as reflected in the molecular dimensions and the planarity of the enaminone portion of the molecule. The molecule has an intramolecular hydrogen bond between the NH and CO groups in the Z configuration, adopting the chelated form. The two pi systems of the molecule (1-methylbenzimidazole and enaminone) are deconjugated and tilted with respect to each other by 15.6 (2) degrees. The solvent water molecule is hydrogen bonded to the N(1) atom of the 1-methylbenzimidazolyl group.

Biological activity of new aza analogues of quinolones.

A series of novel derivatives of 4H-pyrido[1,2-]pyrimidine, 1,4-dihydro-4-oxo-1,5-naphthyridine and 1,4-dihydro-4-oxo-1,6-naphthyridine were prepared and their biological activity was compared with that of nalidixic acid. The in vitro antibacterial activity of the tested compounds was lower than that of nalidixic acid except for two agents, 1b and 2c, with a higher activity against Enterococcus faecalis. The compounds were tested for their ability to cure four plasmids from two species of Enterobacteriaceae. The derivatives eliminated three plasmids (pKM101, pBR322, F'lac) at one-half or one-quarter of the minimal inhibitory concentration. Plasmid RP4 was unaffected by the treatment. None of these compounds showed better antichloroplast activity than nalidixic acid.