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 of novel bioactive molecules. Herein, the synthesis, structural analysis and anticancer activity of the novel triterpenoid thiazole 3 is reported. The synthesis was carried out through the bromination of ochraceolide A (1) and the subsequent heterocyclic condensation with thiourea (overall yield of 80%). The bromination reaction of 1 led to obtain a diastereomeric mixture of 2α- and 2β-bromo ochraceolide A in a ratio of 6:4 (2a and 2b, respectively). Compound 3 was fully characterized by 1D and 2D NMR spectroscopy, FT-IR, HR-MS and single-crystal X-ray diffraction analysis. The triterpenoid thiazole crystallized as an ethyl acetate hemisolvate in the orthorhombic space group P212121 with one molecule of 3 in the asymmetric unit. In the crystal, the molecules interact mainly through N–H⋯N and N–H⋯S hydrogen bonds via a R22 (8) synthon. Hirshfeld surface analysis indicates that the most important contributions to the 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%) and H⋯N/N⋯H (3.5%) interactions. The cytotoxicity and antiproliferative activity of 1, the diastereomeric mixture of 2-bromo ochraceolide A (2a and 2b) and 3 against three cancer cell lines (MCF-7, MDA-MB-231 and SiHa) were investigated. The novel thiazole derivative 3 exhibited significant cytotoxicity and antiproliferative activity against the three cancer cells.