Molecular-docking-guided design, palladium-catalyzed synthesis and anticancer activity of paclitaxel-benzoxazoles hybrids

A series of new paclitaxel-benzoxazoles hybrids were designed based on both the molecular docking mode of beta-tubulin with paclitaxel derivatives (7a and 7g), and the activity-structure relationship of C-13 side chain in paclitaxel. Palladium-catalyzed direct Csp(2)-H arylation of benzoxazoles with different aryl-bromides was used as the key synthetic strategy for the aryl-benzoxazoles moieties in the hybrids. Twenty-six newly synthesized hybrids were screened for their antiproliferative activity against human cancer cell lines such as human breast cancer cells (MDA-MB-231) and liver hepatocellular cells (HepG2) by the MTT assay and results were compared with paclitaxel. Interestingly, most hybrids (7a-7e, 7i, 7k, 71, 7A, 7B, 7D and 7E) showed significantly active against both cell lines at concentration of 50 mu M, which indicated that the hybrid strategy is effective to get structural simplified paclitaxel analogues with high anti-tumor activity.

Automated summary

A series of new paclitaxel-benzoxazoles hybrids were designed based on molecular docking and activity-structure relationship studies. Palladium-catalyzed reactions were used to synthesize the hybrids, and their antiproliferative activity against human cancer cell lines was evaluated. The results showed that the hybrids exhibited high anti-tumor activity.