Aim: To improve the biological activity of A-ring modified analogues of camptothecin.
Methods: A-ring modified camptothecins were synthesized from 10-hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo antitumnor activity against mouse liver cancer H22 was tested. Results Five hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten camptothecin derivatives are new compounds.
Conclusion: The modification of a 1,4-oxazine-2-one ring fused with positions 9 and 10 of A-ring will reduce the antitumor activity of camptothecins.