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. © 2007 Elsevier Masson SAS. All rights reserved.

SARMA M DAS

R GHOSH

A PATRA

B HAZRA

University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

European Journal of Medicinal Chemistry

Glycoside derivatives of diospyrin (1) were synthesized for the first time, and the cytotoxicity of the novel compounds vis-à-vis their precursors were evaluated against two human cancer cell lines, viz. malignant melanoma (A375) and laryngeal carcinoma (Hep2). The IC50 values were in the low micromolar range for all the compounds tested, and A375 cells showed comparatively greater sensitivity than Hep2. Most of the compounds exhibited enhanced activity as compared to the plant-derived quinonoid precursor of the series (1), while the aminophenyl mannosyl (6) was found to be the most effective derivative. In A375 cells, 6 (IC50 = 0.02 M) showed the maximum increase in cytotoxicity (∼35-fold) over that of 1 (IC50 = 0.82 M). Again, when the glycosides were evaluated at a given concentration (0.1 M) for their relative capacity to generate ROS from A375 cells, the compound 6 could produce the highest amount of ROS. Incidentally, this derivative also showed a comparatively lower toxicity (IC50 ∼ 41 M) when tested against normal human peripheral blood mononuclear cells, indicating a fair prospect of its development as a novel chemotherapeutic agent for the treatment of malignant melanoma. © The Royal Society of Chemistry.

Organic and Biomolecular Chemistry

Novel glycoconjugates of diospyrin, a quinonoid plant product: Synthesis and evaluation of cytotoxicity against human malignant melanoma (A375) and laryngeal carcinoma (Hep2)

Isocratic reversed-phase liquid chromatography (LC) method was developed using acetonitrile and water for the determination of diospyrin, a pharmacologically important bisnaphthoquinonoid plant-product. The method was validated for precision, accuracy and reproducibility, and was found to be linear over the concentration range of 1-1000μg/ml; the limits of detection and quantitation were 8 and 20ng, respectively. The technique was used to determine the amount of diospyrin in plant extracts from four climatic regions in India. It was also applied for differentiation and separation of 27 naphthyl compounds. While a composition of 50:50 was preferable for dimeric compounds, the composition 40:60 was a better choice for the monomers. Also, the isomeric α- and β-naphthols and their dimers could be distinguished by conversion into the respective methyl ethers. © 2003 Elsevier B.V. All rights reserved.

Journal of Chromatography A

Liquid chromatographic separation of derivatives of diospyrin, a bioactive bisnaphthoquinonoid plant-product, and analogous naphthyl compounds

Molecular and Cellular Biochemistry

Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line

Chemotherapy

Cytotoxicity of Diospyrin and Its Derivatives in Relation to the Generation of Reactive Oxygen Species in Tumour Cells in vitroandin vivo

Journal of Natural Products

Echinamines A and B, First Aminated Hydroxynaphthazarins from the Sea UrchinScaphechinusmirabilis

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

Journal	European Journal of Medicinal Chemistry
Publisher	-
ISSN	0223-5234