Carbohydrates are diverse and complex compounds with many biological functions. They are a main source of energy for cells but also could inhibit cellular enzymes or be a drug carriers. These properties of carbohydrate are used to develop of new carbohydrate-based therapies which are based on novel functionalization of biologically active carbohydrates. The common modification of carbohydrates is a specific addition of new functional groups which makes them therapeutically useful. In this study we used six CARB-pharmacophores representing different sugar moiety including mono-thio-sugars, 1-4-thio-disaccharides and 4-thiofunctionalized 1,6-anhydro-sugars. They were shown to be cytotoxic in normal glucose medium for cancer cells. When glucose is lowered, CARB-pharmacophores becomes increasingly cytotoxic to human cervix adenocarcinoma (Hela) cancer cells. In low glucose conditions (5 mM), CARB-pharmacophores were more cytotoxic to Hela cells. When, glucose level was increased to 25 mM, cell line become less responsive to CARB-pharmacophores treatment. These results clearly suggest that lower glucose level significantly potentiates CARB-pharmacophores and consequently induce the cell death. The thio-sugar motif appears [1] to be a promising lead for future developments, which warrants further investigation. Acknowledgement This work was supported by the National Science Centre, decision nr DEC-2011/01/B/NZ4/03391 [1]. A Potential CARB-pharmacophore for antineoplastic activity. Part I. Z. J. Witczak, T. Poplawski A. Czubatka, J. Sarnik, P. Tokarz, A. L. VanWert, R. Bielski, Bioorganic & Med. Chem. Lett., 2014, 24, 1752-1757

Low glucose level enhances the cytotoxicity of CARB-pharmacophore to cancer cells

249th National Meeting (2015)

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