Different salt derivatives of phenanthroindolizidine alkaloids display different in vitro antitumor activity

Abstract

Salification is most commonly employed for modifying physical and chemical properties. However, there are few reports on the differences in biological activity between different salt forms and free alkaloids. The salt derivatives of tylophorine and (S)-6-O-desmethylantofine were prepared and systematically evaluated for their antitumor activities against A-549 and HL-60 cell lines. Our bioassay results revealed that different salt derivatives exhibited quite different antitumor activity but the activity did not have a distinct relationship with the strength of the acid or the bonding mode of the alkaloid with the acid. Some of the salt derivatives showed very high in vitro antitumor activity, of which (S)-6-O-desmethylantofine hydroiodide with a low nanomolar level of antitumor activity (GI₅₀: 10 nM for A-549 and HL-60 cell lines) emerged as a new lead for further development as a novel antitumor agent.