Abstract: Several 15,16-epoxy- 8,13,14-labdatriene derivatives modified at the C-16 position with a 1,2,4-oxadiazole ring with various substituent in the 5-th position, were obtained via multistep synthesis from 16-formyl derivatives of natural diterpenoid lambertianic acid. The cytotoxicity of furanolabdanoid-based 1,2,4-oxadiazoles was evaluated against human cancer cells (CEM-13, MT-4, U-937, MCF-7, MDA-MB-231, MEL-8) using the conventional MTT assays. All the tested diterpenoid-oxadiazole hybrids displayed better cytotoxic activity then lambertianic acid. The activity and selectivity to the cell line increased even further in the compounds containing a chloromethyl substituent in the 5th position of the 1,2,4-oxadiazole ring. Two of the synthesized compounds exhibited high cytotoxic activity against lymphoblastoid cell line CEM-13 (GI50 0.08-0.34 mM), which was higher that than of the comparative drug Doxorubicin. The antitumor mechanism may be related to apoptosis induction in U-937, MCF-7, and CEM-13 cells.

Cite: Mironov M.E. , Pokrovsky M.A. , Kharitonov Y.V. , Shakirov M.M. , Pokrovsky A.G. , Shults E.E.
Furanolabdanoid-based 1,2,4-oxadiazoles: Synthesis and cytotoxic activity
ChemistrySelect. 2016. V.1. N3. P.417-424. DOI: 10.1002/slct.201600042 WOS Scopus РИНЦ

Dates:

Published print:	Mar 1, 2016
Published online:	Mar 7, 2016

Identifiers:

Web of science	WOS:000395395200013
Scopus	2-s2.0-85032717594
Elibrary	35506878
OpenAlex	W2294968440

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