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Novel Kojic Acid Derivatives with Potential Biological Activity

Kojic acid can be produced from various carbohydrate sources in an aerobic condition by a variety of microorganisms.1 It contains a polyfunctional heterocyclic skeleton (Fig. 1) with several important reaction centres enabling additional reactions and modifications (alkylation, acylation, a ring opening of the molecule, chelation, etc.). It has been shown that kojic acid and its derivatives possess anti-inflammatory, antifungal and antitumour activity as well as metal ion chelating ability.1 Based on our ongoing study of adamantylated2 and mannosylated3 N-aryl substituted pyridin-4- one derivatives which were synthesized for the purpose of investigating their potential antitumor and hemagglutination properties, respectively, we aim to design new heterocyclic kojic acid derivatives in order to test their biological activities as well. The structure of kojic acid will be modified in several ways: the introduction of adamantyl or α- mannopyranoside unit, ring opening and introduction of nitrogen in the heterocyclic structure. In this work we report the preparation of acylated kojic acid derivatives where adamant- 1-ylacetyl was used as acyl part. The incorporation of adamantyl unit was carried out using Steglich esterification method on both hydroxyl functionalities or selectively on either one by the aid of protecting group tehniques. The prepared compounds will be tested for their in vitro antiproliferative abilities on several human cancer cell lines. We believe that the future studies on biological properties of kojic acid derivatives may lead to the development of a new class of specific and effective pharmaceutical agents. 1. J. Brtko, L. Rondahl, M. Ficková , D. Hudecová, V. Eybl, M. Uher, Cent. Eur. J. Publ. Health, 12 (2004) S16–S18. 2. V. Petrović Peroković, B. Prugovečki, Ž Car, Croat. Chem. Acta 86 (2013) 317-323. 3. Ž. Car, T. Hrenar, V. Petrović Peroković, R. Ribić, M. Seničar, S. Tomić, Chem. Biol. Drug Des. 84 (2014) 393-401.

Kojic acid; Lipophilicity; Antitumor testings; NMR structure caracterization

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