Antimycobacterial activity of diospyrin and its derivatives against Mycobacterium aurum

The objective of this study was to determine the antimycobacterial activity of diospyrin (D1) and four of its derivatives (D2, D5, D7 and D17) against the non-pathogenic Mycobacterium aurum. The effect of these compounds was determined on growth parameters and drug efflux pumping activity. Diospyrin was shown to be the most active in inhibiting the growth of M. aurum whilst D2 was inactive. D17 was found to have the lowest MIC of < 0.1 µg/ml, while the MIC of other compounds were found to be as follows: D1= 0.1 µg/ml, D5= 0.39 µg/ml, D7= 0.78 µg/ml and D2 =3.13 µg/ml, in order of potency. The compounds were bacteriostatic rather than bactericidal as the MBCs were greater than 50 µg/ml. The compounds were potent efflux pump inhibitors as D5 enhanced ciprofloxacin accumulation by 160 %, D17 by 58 %, D7 by 41 %, D1 by 37 % when compared with the standard efflux pump inhibitor, reserpine, which enhanced accumulation by 51 %. D2 had no effect on drug efflux pumping activity. The modifications of diospyrin enhanced the activity of D17 and D5 by decreasing the MIC and enhancing accumulation of ciprofloxacin, respectively. In contrast, activity decreased significantly for D2 in the growth and accumulation assays. Diospyrin and its derivatives are potential antimycobacterial agents and drug efflux inhibitors and could be used to enhance the activity of known antimycobacterial agents that are actively effluxed from M. tuberculosis

The Prospective Role of Plant Products in Radiotherapy of Cancer: A Current Overview

Treatment of cancer often requires exposure to radiation, which has several limitations involving non-specific toxicity toward normal cells, reducing the efficacy of treatment. Efforts are going on to find chemical compounds which would effectively offer protection to the normal tissues after radiation exposure during radiotherapy of cancer. In this regard, plant-derived compounds might serve as “leads” to design ideal radioprotectors/radiosensitizers. This article reviews some of the recent findings on prospective medicinal plants, phytochemicals, and their analogs, based on both in vitro and in vivo tumor models especially focused with relevance to cancer radiotherapy. Also, pertinent discussion has been presented on the molecular mechanism of apoptotic death in relation to the oxidative stress in cancer cells induced by some of these plant samples and their active constituents

Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice

Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from selfhealing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drugresistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches

Antileishmanial and Cytotoxic Compounds from Valeriana wallichii and Identification of a Novel Nepetolactone Derivative

The chloroform extract of Valeriana wallichii (V. wallichii) rhizomes was investigated to elucidate the structures responsible for reported antileishmanial activity. Besides bornyl caffeate (1, already been reported by us previously), bioassay-guided fractionation resulted in two additional cinnamic acid derivatives 2–3 with moderate leishmanicidal activity. The structure of a novel nepetolactone derivative 4 having a cinnamic acid moiety was elucidated by means of spectral analysis. To the best of our knowledge villoside aglycone (5) was isolated from this plant for the first time. The bioassay-guided fractionation yielded two new (compounds 6–7) and two known valtrates (compounds 8–9) with leishmanicidal potential against Leishmania major (L. major) promastigotes. In addition, β-bisabolol (10), α-kessyl alcohol (11), valeranone (12), bornyl isovalerate (13) and linarin-2-O-methylbutyrate (14) were identified. This is the first report on the isolation of 4'-demethylpodophyllotoxin (15), podophyllotoxin (16) and pinoresinol (17) in V. wallichii. In total thirteen known and four new compounds were identified from the extract and their cytotoxic and antileishmanial properties were evaluated

CLSI-Derived Hematology Reference Intervals for Healthy Males in Eastern India

Haematological reference ranges are often influenced by individual variables, such as race, age, gender and dietary habits. In addition, ecological factors such as climate and altitudemight affect the parameters, while variations in instrumentation techniques and laboratory personnel involved also contribute to the measurements. Therefore, the currently used reference ranges, which were originally adopted from other countries and mainly refer to European subjects, might be misleading in some cases. This study is an attempt to establish haematological reference ranges for male subjectsfrom Eastern India. Haematological tests, using an automated haematology analyzer, were carried out on 528blood samples from healthy male donors. The population was found to exhibit lowerhaemoglobin (HGB) and platelet (PLT) contents as compared to the standard reference values, although the difference was statistically significant only for the platelet count. Nevertheless, the digression from the international range of data was clinically significant, except for the white blood cells (WBC) and red blood cells (RBC) counts. Finally, the respective reference values for HGB, RBC and hematocrit (HCT) were found to vary significantly with the age group of the subjects. It is expected that the study will facilitate the interpretation and reporting of haematological parameters in Eastern India

Diospyrin, A Bisnaphthoquinone: A Novel Inhibitor of Type I DNA Topoisomerase of Leishmania donovani

Diospyrin is a plant product that has significant inhibitory effect on the growth of Leishmania donovani promastigotes. This compound inhibits the catalytic activity of DNA topoisomerase I of the parasite. Like camptothecin, it induces topoisomerase I mediated DNA cleavage in vitro. Treatment of DNA with diospyrin before addition of topoisomerase I has no effect. Preincubation of topoisomerase I with diospyrin before the addition of DNA in the relaxation reaction increases this inhibition. Our results suggest that this bis-naphthoquinone compound exerts its inhibitory effect by binding with the enzyme and stabilizing the topoisomerase I-DNA “cleavable complex.” Diospyrin is a specific inhibitor of the parasitic topoisomerase I. It does not inhibit type II topoisomerase of L. donovani and requires much higher concentrations to inhibit type I topoisomerase of calf thymus. The potent inhibitory effect of diospyrin on type I DNAtopoisomerase from L. donovani can be exploited for rational drug design in human leishmaniasis

Novel Glycoconjugates of Diospyrin, a Quinonoid Plant product: Synthesis and Evaluation of Cytotoxicity Against Human Malignant Melanoma (A375) and Laryngeal Carcinoma (Hep2)

Glycoside derivatives of diospyrin (1) were synthesized for the first time, and the cytotoxicity of the novel compounds vis-`a-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 lM) showed the maximum increase in cytotoxicity (∼35-fold) over that of 1 (IC50 = 0.82 lM). Again, when the glycosides were evaluated at a given concentration (0.1 lM) 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 lM) 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

Determination of sugar acids and related compounds by vanadium(V) in perchloric acid: The product analysis and probable mechanism of oxidation

1099-1101A mixture of the reductant and an excess of Na(or NH4)VO3, in dilute HClO4 has been slowly refluxed for 40 min and the residual metavanadate determined iodometrically. The metavanadate has been standardized against either Na2S2O3 or the respective reductant of known strength for better results. The product analysis, the probable reaction mechanism, the methods for removal of interferants and the detection of adulterants in aldoses have been reported