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Synthesis and antitumor activity of pyrano[3,2-i]-fused camptothecin derivatives

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Abstract

A novel series of A-ring modified hexacyclic camptothecin derivatives containing a pyranone ring fused at the 9-positions and 10-positions were designed and synthesized. These new derivatives were screened against four human tumor cell lines and the results showed most of the compounds possessed comparable cytotoxicity to 10-hydroxycamptothecin (HCPT) in vitro. The pyranono-fused derivatives, except for the one with methoxyformyl group at 4′-position (12), displayed similar inhibitory efficiency to saturated dihydropyrano-fused camptothecins (6 and 7) and superior cytotoxic activity compared with topotecan (TPT). These results indicated that the saturated and unsaturated fused-pyran rings would not disrupt the base-stacking between camptothecins and the DNA base pair, as well as the interactions between the compounds and Topoisomerase I.

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Acknowledgements

This work was supported by Shanghai Committee of Science and Technology of China (No.14431900600) and the Scientific Research Foundation of the Third Institute of Oceanography, SOA (No. 2018013).

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Correspondence to Qian Zhang.

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Hong, B., Meng, G., Tan, H. et al. Synthesis and antitumor activity of pyrano[3,2-i]-fused camptothecin derivatives. Med Chem Res 28, 884–891 (2019). https://doi.org/10.1007/s00044-019-02342-4

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