Synthesis of plumbagin derivatives and their inhibitory activities against Ehrlich ascites carcinoma in vivo and Leishmania donovani Promastigotes in vitro

Abstract

Plumbagin, a plant-derived bioactive naphthoquinonoid compound, was converted to a hydroquinonoid derivative, which was studied for its tumour-inhibitory and antileishmanial activities for the first time. A similar chemical transformation was undertaken on an analogous dimeric compound, diospyrin, and its bioassay results were compared with those of the plumbagin derivative. Synthesis of the derivative of plumbagin did not result in a marked enhancement of the tumour-inhibitory activity, whereas the improvement was obvious in the case of diospyrin vis à vis its hydroquinonoid analogue. The conversion of diospyrin to the hydroquinonoid compound also led to a substantial increase in the antileishmanial activity, while a similar conversion of plumbagin failed to do so.

Larvicidal activity of extracts from three Plumbago spp against Anopheles gambiae

“…The stereochemistry at the C-24 asymmetric centre was investigated by a careful comparison with the 1 H NMR spectra of both epimers at C-24 in similar steroids (Gamze et al 2002). The steroid was obtained as colourless crystals (13 mg Though compounds 1 and 2 have been reported elsewhere in literature (Dey & Harbone 1991, Hazra et al 2002, this is the first time they are being reported from the Plumbago species growing in Kenya.…”

“…-This was obtained from fraction Fr 12-34 and identified from 1D and 2D NMR data, mass spectral data and by comparing these spectroscopic data with those reported in literature. Plumbagin (Figure) was obtained as bright yellow needles (401 mg), mp 77.8-77.4°C [literature value 76.8-77.4°C (Dinda et al 1998, Hazra et al 2002 -6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol (β-Sitosterol) -This compound (Figure) was identified by comparing the spectral data obtained with those reported in the literature (Dey & Harbone 1991). The stereochemistry at the C-24 asymmetric centre was investigated by a careful comparison with the 1 H NMR spectra of both epimers at C-24 in similar steroids (Gamze et al 2002).…”

Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Suppresses NF-κB Activation and NF-κB-regulated Gene Products Through Modulation of p65 and IκBα Kinase Activation, Leading to Potentiation of Apoptosis Induced by Cytokine and Chemotherapeutic Agents

“…Plumbagin has been shown to exert anticancer and antiproliferative activities in animal models as well as in cells in culture (7)(8)(9)(10)(11). Sugie et al (12) have shown that plumbagin significantly inhibited azoxymethane-induced intestinal carcinogenesis in rats, suggesting its chemopreventive activity (12).…”

“…The cytotoxic action of plumbagin in keratinocytes and cervical cancer cells was found to be due to a change in the redox status of the cell (6,15). In embryonic kidney and brain tumor cells, plumbagin inhibited the enzyme NAD(P)H oxidase (16), linked with anticarcinogenic (7)(8)(9)(10)(11)(12) and atherosclerotic effects (17). Besides anticancer effects, plumbagin also exhibited radiosensitizing properties in experimental mouse tumors as well as in tumor cells in vitro (18 -20).…”

Antileishmanial activity of lapachol analogues

“…Quinones, in general, and, particularly hydroxyquinones, as well as their reduced derivatives, have been tested against several parasite species (Croft et al 1992, Sauvain et al 1993, Iwu et al 1994, Ray et al 1998, Kayser et al 2000, Ferreira et al 2002, Hazra et al 2002 and low bioavailability (Kayser et al 2000). Atovaquone, a hydroxynaphtoquinone, showed to have a concentration-dependent in vitro activity against L. infantum (Jernigan et al 1996), while the in vivo activity in a murine model remained low (Murray et al 1996, Cauchetier et al 2000.…”