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e coumarin derivatives are quite interesting objects for both synthesis and pharmacological screening. Major problems in medicine today include resistance to drugs, where a number of enzymes and receptors important for the tumour cell cycle progression may be considered as potential targets for new drugs. Presented study was aimed to evaluate in vitro antiproliferative effects of previously synthesized benzylidene-bis-(4hydroxycoumarin) derivatives and fused benzopyranocoumarin derivatives. Compounds were tested on HeLa, SW620, MiaPaCa-2, MCF-7, HepG2 and WI-38 cell lines. The most potent compounds were subjected to molecular docking simulations in order to reveal binding modes and mechanism of interaction of synthesized compounds with target receptors. Furthermore, physicochemical properties included in Lipinski's rule of 5 and polar surface area were calculated to determine compounds’ solubility properties and their appropriateness for oral intake in humans. Keywords: benzylidene-bis-(4-hydroxycoumarin) derivatives, fused benzopyranocoumarin derivatives, antiproliferative evaluation, docking study, bioavailability.

1

INTRODUCTION

The coumarin (2-oxo-2H-chromene) derivatives are quite interesting objects for both synthesis and pharmacological screening. A variety of synthesized coumarin derivatives have been experimentally shown to exert broad spectrum of pharmacological activities [1-8]. Nowadays we face some major problems in medicine, including resistance to antibiotics and lacking of cure for © Springer Nature Singapore Pte Ltd. 2017 A. Badnjevic (ed.), CMBEBIH 2017, IFMBE Proceedings 62, DOI: 10.1007/978-981-10-4166-2_112

some chronic diseases and cancer. Related to the problem of cancer cells resistant to treatments, a number of enzymes and receptors important for the tumor cell cycle progression may be considered as potential targets for new drugs. As such validated targets are recognized as major pillars in the drug discovery and drug development process, a number of in silico methods are used to identify potential targets and interactions of small molecules with target proteins in the cell. Among them, molecular docking is a popular method to study binding of small molecules (ligands) to macromolecules (receptor). In particular, the efficiency of Autodock program has been well demonstrated for that purpose in several studies [9-11]. Presented study was aimed to evaluate in vitro antiproliferative effects of synthesized benzylidene-bis-(4hydroxycoumarin) derivatives and fused benzopyranocoumarin derivatives. The most potent compounds were subjected to molecular docking simulations in order to reveal binding modes and mechanism of interaction of synthesized compounds with target receptors. Furthermore, physicochemical properties included in Lipinski's rule of 5 and polar surface area were calculated to determine compounds’ solubility properties and their appropriateness for oral intake in humans [12,13].

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MATERIALS AND METHODS

Structures of eight previously synthesized biscoumarin derivatives [7] that

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