Synthesis, structure analysis and activity against breast and cervix cancer cells of a triterpenoid thiazole derived from ochraceolide A

Abstract

The structural modification of natural products has shown to be a remarkable tool in the generation ofnovel bioactive molecules. Herein, the synthesis, structural analysis and anticancer activity of the noveltriterpenoid thiazole3is reported. The synthesis was carried out through the bromination of ochra-ceolide A (1) and the subsequent heterocyclic condensation with thiourea (overall yield of 80%). Thebromination reaction of1led to obtain a diastereomeric mixture of 2a- and 2b-bromo ochraceolide A in aratio of 6:4 (2aand2b, respectively). Compound3was fully characterized by 1D and 2D NMR spec-troscopy, FT-IR, HR-MS and single-crystal X-ray diffraction analysis. The triterpenoid thiazole crystallizedas an ethyl acetate hemisolvate in the orthorhombic space groupP212121with one molecule of3in theasymmetric unit. In the crystal, the molecules interact mainly through NeH/N and NeH/S hydrogenbondsviaaR22(8) synthon. Hirshfeld surface analysis indicates that the most important contributions tothe crystal packing are from H/H (69.5%), H/O/O/H (16.4%), H/C/C/H (5.5%), H/S/S/H (4.6%) andH/N/N/H (3.5%) interactions. The cytotoxicity and antiproliferative activity of1, the diastereomericmixture of 2-bromo ochraceolide A (2aand2b) and3against three cancer cell lines (MCF-7, MDA-MB-231 and SiHa) were investigated. The novel thiazole derivative3exhibited significant cytotoxicity andantiproliferative activity against the three cancer cells.