Chirality in Anticancer Agents

Many drugs are chiral and their therapeutic activity depends on specific recognition of chiral biomolecules. The biological activity of enantiomers can also differ drastically in terms of toxicity and pharmacokinetics. Chiral natural biological molecules, such as nucleic acids, enzymes are targeted molecules for the development of anticancer drugs. The interest in chiral agents is logically a result of the different interaction with biomolecules leading in the end consequence to improve anticancer activity and maybe to less undesirable effects. This review outlines the effects of chirality on the efficiency of anticancer metal-based agents and potential organic drugs. A variety of up-to-date examples of structurally diverse chiral agents exhibiting different mechanisms in their antitumor activity is presented

Experience the czech population with age discrimination

Abstract. At present ageism is a commencing problem which is necessary to deal with. Originally an English term has no Czech equivalent and it denotes discrimination or differentiation on the basis of age implying prejudices towards elderly people. It concerns statements and attitudes without true and reasonable basis. Some manifestations of discrimination are evident, some remain not pronounced in vertones. Ageism appears most often in the sphere of employment, where people are rejected for the reason of alleged decreasing performance and frequent sickness, according to prejudices connected with their more advanced age. The practical part of my thesis aims at a comparison of people over 50 and those who are still under this imaginary limit. By collecting primary data the following hypothesis was tested among others: it is more difficult for people over 50 to find work than for younger age categories. Respondents were chosen among job applicants of the Job Centre in Tábor. On the basis of a questionnaire and a secondary analysis of the data it was proved that 50+ applicants at the Job Centre in Tábor had to face age discrimination at an interview more often and also have more frequent experience with being dismissed due to their advanced age, which confirms the determined hypothesis. It is interesting that as people grow old they tend to think that after being 50 their work performance will decrease. Moreover, the research implies in general that people over 50 are a worse employable group than those of lower age categories. A feasible solution of this situation might be adjusting of stricter recourses for this kind of discrimination. In the Czech Republic this problem has been treated directly only under the rule of employment law which bans this kind of discrimination. A possible contribution might be an anti-discrimination law now being prepared. Promoting the effort to change social awareness concerning the qualities and abilities of older generation is also essential. Media should present a more positive image of elderly people; after all decreasing strength is compensated by great life experience, therefore this combination may not influence their general ability and performance

Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis

β2-Agonists (β2-adrenergic agonists, bronchodilatants, and sympathomimetic drugs) are a group of drugs that are mainly used in asthma and obstructive pulmonary diseases. In practice, the substances used to contain one or more stereogenic centers in their structure and their enantiomers exhibit different pharmacological properties. In terms of bronchodilatory activity, (R)-enantiomers showed higher activity. The investigation of stereoselectivity in action and disposition of chiral drugs together with the preparation of pure enantiomer drugs calls for efficient stereoselective analytical methods. The overview focuses on the stereoselectivity in pharmacodynamics and pharmacokinetics of β2-agonists and summarizes the stereoselective analytical methods for the enantioseparation of racemic beta-agonists (HPLC, LC-MS, GC, TLC, CE). Some methods of the stereoselective synthesis for β2-agonists preparation are also presented

Survey of Pharmacological Activity and Pharmacokinetics of Selected β-Adrenergic Blockers in Regard to Their Stereochemistry

The present survey concentrates on pharmacodynamics and pharmacokinetics of selected β-adrenergic blockers from the point of view of their stereochemistry. It could be shown that the activity in the arylaminoethanol and aryloxyaminopropanol group of β-blockers is higher in their (–)-enantiomers as compared with the (+)-enantiomers. The stereoisomers differ also in other types of bioactivity as well as in toxicity. The particular pharmacokinetic stages such as resorption, distribution, and metabolism are discussed in regard to their stereochemistry

Chiral Aspects of Local Anesthetics

Thanks to the progress made in chemical technology (particularly in the methodologies of stereoselective syntheses and analyses) along with regulatory measures, the number of new chiral drugs registered in the form of pure enantiomers has increased over the past decade. In addition, the pharmacological and pharmacokinetic properties of the individual enantiomers of already-introduced racemic drugs are being re-examined. The use of the pure enantiomer of a drug that has been used to date in the form of a racemate is called a “chiral switch”. A re-examination of the properties of the pure enantiomers of racemates has taken place for local anesthetics, which represent a group of drugs which have long been used. Differences in (R) and (S)-enantiomers were found in terms of pharmacodynamic and pharmacokinetic activity as well as in toxicity. Levobupivacaine and robivacaine were introduced into practice as pure (S)-(−)-enantiomers, exhibiting more favorable properties than their (R)-(+)-stereoisomers or racemates. This overview focuses on the influence of chirality on the pharmacological and toxicological activity of local anesthetics as well as on individual HPLC and capillary electrophoresis (CE) methods used for enantioseparation and the pharmacokinetic study of individual local anesthetics with a chiral center

Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans. All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid

Bipyridine Ruthenium(II) Complexes with Halogen-Substituted Salicylates: Synthesis, Crystal Structure, and Biological Activity

Ruthenium complexes currently represent a perspective subject of investigation in terms of potential anticancer therapeutics. Eight novel octahedral ruthenium(II) complexes are the subject of this article. Complexes contain 2,2′-bipyridine molecules and salicylates as ligands, differing in position and type of halogen substituent. The structure of the complexes was determined via X-ray structural analysis and NMR spectroscopy. All complexes were characterized by spectral methods—FTIR, UV–Vis, ESI-MS. Complexes show sufficient stability in solutions. Therefore, their biological properties were studied. Binding ability to BSA, interaction with DNA, as well as in vitro antiproliferative effects against MCF-7 and U-118MG cell lines were investigated. Several complexes showed anticancer effects against these cell lines

Antiproliferative Ruthenium Complexes Containing Curcuminoid Ligands Tested In Vitro on Human Ovarian Tumor Cell Line A2780, towards Their Capability to Modulate the NF-κBTranscription Factor, FGF-2 Growth Factor, and MMP-9 Pathway

So far, the polyphenolic components of turmeric have shown a significant pharmacological preventative activity for a wide spectrum of diseases, including oncological disorders. This type of natural product could be of great interest for the inhibition of cancer cell proliferation, displaying less side effects in comparison to classical chemotherapeutics. The poor bioavailability and quick metabolism of such natural compounds require new investigative methods to improve their stability in the organisms. A synthetic approach to increase the efficiency of curcuminoids is to coordinate them to metals through the beta-dicarbonyl moiety. We report the synthesis and the biological attempts on human ovarian carcinoma A2780 of ruthenium(II) complexes 1–4, containing curcuminoid ligands. The cytotoxicity of complexes 1–4 proves their antiproliferative capability, and a correlation between the IC50 values and NF-κB transcription factor, FGF-2, and MMP-9 levels was figured out through the principal component analysis (PCA)