Ponente
Descripción
Several natural product peptides and depsipeptides discovered over the last decades show potent anticancer activity, typically behaving as antimitotic agents through the inhibition of microtubule assembly.1 These include hemiasterlin, dolastatin 10 and 15, cryptophycin and tubulysins. The derivatization of these cytotoxic peptides has proven effective for the development of novel anticancer agents, including their conjugates to targeting agents such as antibodies and peptide ligands. For example, taltobulin (HTI-286), a synthetic analog of tripeptide hemiasterlin in which the indole group was replaced by a phenyl, is a promising anticancer agent that has advanced to clinical trials.2 Similarly, several dolastatin analogs have been produced for clinical evaluation as anticancer agents. In this job, we proposal the synthesis of some Dolastatin 15 based cytotoxic peptide candidates using the potentialities of SPPS. All cytotoxic peptide synthesized were analized by proton and carbon NMR, and also, through of HR-ESI-MS and analytical RP-HPLC. Furthermore, these compounds were tested to determine the viability of HCT-116 cells after 48 hours compound incubation showing activity in the order of submicromolar values. Summarizing, several candidates of cytotoxic peptides were synthesized on solid phase with high purity and properly values of anticancer activity to use them as prospective anticancer therapeutic agents.
