Due to a poor clinical predictive power of 2D cell cultures, standard tool for in vitro assays in drug discovery process, there is increasing interest in developing 3D in vitro cell cultures, biologically relevant assay feasible for the development of robust preclinical anti-cancer drug screening platforms. Herein, we tested amidino-substituted benzimidazoles and benzimidazo[1,2-a]quinolines as a small platform for comparison of antitumor activity in 2D and 3D cell culture systems and correlation with structure-activity relationship. 3D cell culture method was applied on a human cancer breast (SK-BR-3, MDA-MB-231, T-47D) and pancreatic cancer cells (MIA PaCa-2, PANC-1). Results obtained in 2D and 3D models were highly comparable, but in some cases we have observed significant disagreement indicating that some prominent compounds can be discarded in early phase of researching because of compounds with false positive result. To confirm which of cell culture systems is more accurate, in vivo profiling is needed. Keywords

in 3D format will be shown. Conclusions: Although biological significance of obtained data from 2D and 3D cell cultures is still poorly understood, discrepancy of compunds activity illustrated importance of implementation 3D cell culture assays in early part of drug discovery process.IntroductIon T he costs for successfully introduction a NCE (new chemical entity) drug compound to the market is between $800 million and $1,2 billion, with an average duration of about 10 -15 years. Expenses are even much higher in the case of late stage failure (or failure of already marketed drug) (1). Analyses of clinical trials reveal that about 67% of drug lead molecules fail in late clinical trials stages, most of them due to poor efficacy and safety issues. This high attrition rate indicate that current pre-clinical screening and in vitro models do not adequately provide critical information required for prediction of efficacy and safety issues, which remain the main reasons for drug failure (2). The ability of an assay to produce reliable information about tested NCEs is essential in drug development. Therefore, one way to improve drug dis-

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Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton–McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.

Background and purpose: Producing of reliable information about pharmacological activity of new chemical entities is essential in early stages of drug discovery and development. There is a continuous need for improvement of existing in vitro technologies, in order to get more accurate and more predictive biological data (and for compounds selection) in pre-clinical screening methods and models. Materials and methods: Two-dimensional (2D) cell cultures, in comparison with original tissues, does not fully reproduce in vivo cell growth and differentiation. Therefore, significant efforts have been made toward the development of more realistic three-dimensional (3D) in vitro cell culture models that would better mimic tissue physiology. Results: Two-dimensional (2D) cell cultures, in comparison with original tissues, does not fully reproduce in vivo cell growth and differentiation. Therefore, significant efforts have been made toward the development of more realistic three-dimensional (3D) in vitro cell culture models that would better mimic tissue physiology. Basic concepts and advantages of 3D cell cultures, as well as different approaches in technologies that enable the cell growth in 3D will be presented here. Possible applications of 3D cell culture in drug discovery will be discussed, and example of formation of spherical growth of three different human breast cancer cells (MDA-MB-231, SK-BR-3 and T-47D cells) in 3D format will be shown. Conclusions: Although biological significance of obtained data from 2D and 3D cell cultures is still poorly understood, discrepancy of compunds activity illustrated importance of implementation 3D cell culture assays in early part of drug discovery process. Keywords: new anticancer drugs, in vitro assays 2D and 3D cell cultures, 3D cell cultures technologies, applications in drug discovery