Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids

摘要

A series of acetylenic derivatives of betulonic and betulinic acids has been synthesized and characterized by H-1 and C-13 NMR, IR and MS spectroscopy. The structure of propargyl betulonate 4 and propargyl betulinate-DMF solvate 8A was solved by X-ray diffraction. Thermal properties were examined using a DSC technique. The resulting alkynyl derivatives, as well as betulin 1 and betulinic acid 3, were evaluated in vitro for their cytotoxic activity against human T47D breast cancer, CCRF/CEM leukemia, SW707 colorectal, murine P388 leukemia and BALB3T3 normal fibroblasts cell lines. Several of the obtained compounds have a favorable cytotoxic profile than betulin I Propargyl betulinate 8 was the most active derivative, being up to 3-fold more potent than betulin I against the human leukemia (CCRF/CEM) cell line, with an IC50 value of 3.9 mu g/mL. (C) 2015 Elsevier B.V. All rights reserved.