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 (approximately 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 microM) 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 microM, respectively) in comparison to the natural precursor, diospyrin (IC50=0.82 and 3.58 microM, respectively). Moreover, diospyrin and all its derivatives were found to show significantly greater (approximately 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.
Das Sarma
Madhushree
M
Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032, West Bengal, India.
Ghosh
Rina
R
Patra
Amarendra
A
Hazra
Banasri
B
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016227:Benzoquinones / Q000737:chemistry*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004563:Electrochemistry; D006801:Humans; D051379:Mice; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000473:pathology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D016227:Benzoquinones; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C004532:quinone; C043546:diospyrin