In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs (3g and 3f) showed better anti-hepatocarcinoma activity than CPT. Compounds 3d, 3e, 3g, 3h and 3i also showed strong inhibition activity against BGC803. Graphic abstract

A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of β-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated β-anhydroicaritine derivatives were synthesised using this methodology. These newly synthesised derivatives, especially the compounds 5b, 5c and 5j, significantly suppressed cell proliferation when tested against cancer cell lines in vitro. Compound 5j (R = Bn) exhibited a competitive inhibition against MCF7 in vivo compared to tamoxifen. Graphical Abstract