Hybrid compounds of sclareol and doxorubicin, their synthesis and application

Abstract

The invention represents new hybrid compounds of two natural products sclareol and doxorubicin in the form of their conjugates. These compounds are in the form of conjugates, where doxorubicin and sclareol are covalently linked by a linker in a 1:1 molar ratio. The hybrids have shown to possess anticancer properties and are effective in treating resistant cancer cells that have P-glycoprotein membrane transporter, responsible for resistance to doxorubicin. The hybrids have been tested on different types of cell lines, including human glioblastoma, non-small cell lung carcinoma, and colorectal carcinoma. Also, a method for their preparation and their use in medical products or pharmaceutical preparations has been determined. The results of the study include the cytotoxic activity of single, combined, and conjugated compounds in pairs of sensitive and resistant cancer cells, with and without P-glycoprotein expression. The selectivity towards cancer cells was determined by comparing with commercially available normal human lung fibroblast cells. The study also investigated the nanoparticle nature of hybrid compounds, their intracellular localization and toxicity in vivo.

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