Synthesis of novel aminoquinonoid analogues of diospyrin and evaluation of their inhibitory activity against murine and human cancer cells

The synthesis and tumor-inhibitory activity of a series of aminonaphthoquinone derivatives of diospyrin, which was isolated from Diospyros montana Roxb., are presented here for the first time. An aminoacetate derivative showed the maximum (∼93%) increase in life span in vivo against murine Ehrlich ascites carcinoma (EAC) at a dose of 1 mg kg−1 day−1 (ip; five doses), and the lowest IC50 (0.06 μM) in vitro. Further, the same analogue also exhibited considerable enhancement in antiproliferative activity when evaluated against human cell lines, viz. malignant skin melanoma and epidermoid laryngeal carcinoma (IC50 = 0.06 and 0.92 μM, respectively) in comparison to the natural precursor, diospyrin (IC50 = 0.82 and 3.58 μM, respectively). Moreover, diospyrin and all its derivatives were found to show significantly greater (∼17- to 1441-fold) cytotoxicity against the tumor cells as compared to normal human lymphocytes. All these quinonoids generated substantial amounts of reactive oxygen species in EAC cells, more or less commensurate to their respective IC50 values.

Graphical abstract Site-specific amination of diospyrin, isolated from Diospyros montana Roxb., produced derivatives with variable antitumor activity against two human cell lines and a murine tumor model.Figure optionsDownload full-size imageDownload as PowerPoint slide