A Series of Azepano‐Betulins with Cytotoxic Activity

Abstract A series of lupane‐type A‐ring azepanes modified at the C28, C30 positions and NH‐group have been synthesized and evaluated for cytotoxic activity against the NCI‐60 cancer cell line panel. Azepano‐betulinic amides showed pronounced activity, with a GI 50 range from 0.57 μM to 14.30 μM, being 4–5 times more active than doxorubicin against colon cancer HCT‐15 and ovarian cancer NCI/ADR‐RES. It was established that azepano‐betulinic cyclohexyl‐amide acts preferentially through apoptosis induction both in conditionally normal and tumor cells, demonstrating mainly cytotoxic properties, whereas earlier studied azepano‐betulin acted by triggering the cell cycle arrest in cancerous cells and displayed mostly cytostatic activity. The crystal structure of N ‐methyl‐azepano‐betulin hydrochloride salt was established by X‐ray diffraction method.