Synthesis and assessment of cytotoxicity of the phlomisoic acid methyl ester derivatives containing 1,3,4-oxadiazolylcarbonyl substituent on the furan ring
M. E. MIRONOV1,2, M. A. POKROVSKY1,2, A. G. POKROVSKY2, YU. V. KHARITONOV1, E. E. SHULTS1
1Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Novosibirsk State University, Novosibirsk, Russia
Keywords: diterpenoids, furanolabdanoids, phlomisoic acid, hydrazines, heterocyclisation, 1,3,4-oxadiazoles, cytotoxicity
Abstract
A new synthetic approach has been developed on the structure modification of bioactive furanolabdanoid phlomisoic acid methyl ester by introducing 1,3,4-oxadiazolylcarbonyl fragment at position 16 of the carbon framework. The key steps of the synthesis are the preparation of (2-(2-(aryloyl/hetaryloyl)hydrazinyl)-2-oxoacetyl)furans and their subsequent heterocyclisation proceeding under the action of dehydrating agents. The cytotoxic properties of the obtained compounds were evaluated with MTT test against three human cancer cell lines. It has been shown that introduction of (5-(pyridin-4-yl)-1,3,4-oxadiazol-1-yl)methanone motif on the furan ring of the starting labdanoid significantly increases the cytotoxic action.
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