Phytochemical investigation of the leaves of Lepisanthes rubiginosa led to the isolation of two new glycosides, lepisantheside A (1) and lepisantheside B (2), together with two known compounds acutoside A (3) and 3-O-[β-D-xylopyranosyl-(1→3)-β-Dglucopyranosyl-]-oleanolic acid (4). Their structures were elucidated by means of spectroscopic methods (HRESIMS, 1D and 2D NMR), and by comparison with the reported data. The cytotoxicity of compounds 1 -4 against four human cancer cell lines (KB, HepG2, SK-LU-1 and MCF7) was evaluated. Compound 4 exhibited significant activity with IC 50 values of 9. 57, 6.66, 6.97 and 18.32 µM, respectively, in comparison with the postive control ellipticine.

Synthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic acids and an unsaturated tubuphenylalanine moiety, respectively, were described. The in vitro cytotoxic activity by SRB assay on five cancer cell lines for sixteen tubulysins was evaluated. Among them, five analogues exhibited strong cytotoxic activities against five human cancer cell lines, including human breast carcinoma (MCF7), human colorectal adenocarcinoma (HT-29), HL-60, SW-480, human lung adenocarcinoma (A459). Interestingly, one analogue showed the strongest cytotoxicity on all five tested cell lines even much higher toxicity than the reference compound ellipticine.