Synthesis and Biological Evaluation of Chalcones having Heterosubstituent(s).

Chalcones and their synthetic analogues appear to have the same binding site of tubuline as phenstatin, combretastatin steganacin and podophylotoxin and are therefore capable to inhibit cancer cell proliferation. The phenyl rings with appropriate substitutions maintain a fixed distance between two centers of aryl rings. The two aromatic rings in these molecules are arranged like the two wings of a butterfly having certain dihedral angle between them, therefore a "butterfly model" is proposed an important structural feature responsible for their antitubulin activity. In this sequence a series of chalcones were synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. In addition the synthetics reduced MIC of ciprofloxacin upto four fold this indicates their bioavailability enhancing potential.

Immunomodulatory activity of biopolymeric fraction RLJ-NE-205 from Picrorhiza kurroa.

In the last three decades, numerous biopolymeric fractions have been isolated from medicinal plants and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulatory effects. The biopolymeric fraction RLJ-NE-205 was isolated and purified from the rhizomes of Picrorhiza kurroa. We evaluated the effects of biopolymeric fraction RLJ-NE-205 from P. kurroa on the in vivo immune function of the mouse. Balb/c mice were treated with the biopolymeric fraction RLJ-NE-205 (12.5, 25 and 50 mg/kg body weight) for 14 days with sheep red blood cells (SRBC) as an antigen. Haemagglutination antibody (HA) titre, plaque forming cell (PFC) assay, delayed type hypersensitivity (DTH) reaction, phagocytic index, proliferation of lymphocytes, analysis of cytokines in serum and CD4/CD8 population in spleen (determined by flowcytometry) were studied. At the dose of 50 mg/kg, significant increases in the proliferation of lymphocytes (p<0.001) and cytokine levels (IL-4 and IFN-gamma) in serum (p<0.001) were observed. A dose dependent increase was demonstrated in HA titre (p<0.05), DTH (p<0.01), PFC (p<0.05), phagocytic index (p<0.05) and CD4/CD8 (p<0.01) population. This suggests that the biopolymeric fraction RLJ-NE-205 improves the immune system and might be regarded as a biological response modifier.

Isolation, structure elucidation and in vivo hepatoprotective potential of trans-tetracos-15-enoic acid from Indigofera tinctoria Linn.

The bioassay guided fractionation of the dried aerial part of Indigofera tinctoria Linn. led to the identification of an active fraction labelled as indigotin. On further chemical analysis, a compound isolated from indigotin was identified and characterized as trans-tetracos-15-enoic acid (TCA). The chemical structure of this compound was established on the basis of physical properties and spectral data, including NMR. It afforded significant hepatoprotection against carbon tetrachloride and paracetamol induced hepatotoxicity in experimental models. Silymarin, a well known plant based hepatoprotective agent, and N-acetylcysteine, which has proven efficacy as a replenisher of sulfhydryls, were used for relative efficacy. TCA was found to reverse the altered hepatic parameters in experimental liver damage. In the safety evaluation study the oral LD50 was found to be more than 2000 mg/kg, with no signs of abnormalities or any mortality for the 15 day period of observation after administration of a single dose of drug in mice. The studies revealed significant and concentration dependent hepatoprotective potential of TCA as it reversed the majority of the altered hepatic parameters in experimental liver damage in rats and mice and may be useful in the management of liver disorders.

Preparative high-performance liquid chromatographic separation of naphthodianthrones from St. John's Wort.

St. John's Wort (Hypericum perforatum), a perennial flowering plant, has been used medicinally for thousands of years and has most recently been identified as an effective treatment for mild to moderate depression and neuralgic disorders. This work presents a procedure for the isolation of naphthodianthrones from St. John's Wort by an accelerated extraction and separation of marker compounds by preparative high-performance liquid chromatography (HPLC) with photodiode array detection. The accelerated extraction method minimizes the extraction time and increases the yield, and the marker compounds obtained by preparative HPLC are of 98% purity. The compounds are characterized by liquid chromatography-mass spectrometry (electrospray ionization) and NMR spectra.

Synthesis and bronchodilator activity of new quinazolin derivative.

Taking lead from a naturally occurring quinazolin vasicine, a number of compounds were developed and evaluated for bronchodilator and anti-allergic activities. One of these compounds was 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino[2,1-b]quinazolin-12-one, hereinafter named 95-4, exhibited marked bronchodilator activity evaluated on contracted trachea or constricted tracheo-bronchial tree. On intestinal smooth muscle too it showed relaxant effect. Tracheal relaxant effect was not found to be mediated through beta-adrenoceptors. Cumulative dose-response study with acetylcholine and histamine indicated for its non-specific direct effect on smooth muscles. 95-4 was found to be more potent than theophylline and less to that of salbutamol on dose basis. Tested by a number of experimental models, it was found devoid of anti-allergic activity. It was also found to be free from any adverse effect. 95-4 due to its marked bronchial muscle relaxant effect can find use in conditions associated with spasm of bronchial muscles.

Immunopotentiating properties of Cryptolepis buchanani root extract.

The ethanol extract (95%) of the root of the plant Cryptolepis buchanani (EECB) was investigated for immunomodulatory activity in mice and rats. The oral administration of EECB caused significant stimulation of the delayed type hypersensitivity (DTH) reaction and humoral antibody production. The oral LD50 was found to be more than 3 g/kg in both rats and mice.

A simple and reliable semipreparative high-performance liquid chromatography technique for the isolation of marker-grade hyperforin from Hypericum perforatum L extract.

The present work describes isolation of bioactive lipophilic constituent [namely, hyperforin from St. John's wort (Hypericum perforatum L.)], of approximately 98% purity by semipreparative high-performance liquid chromatography (LC). The extraction, isolation, and analysis of the collected compound is performed without the use of antioxidants and inert gas atmospheres at all the stages. Hyperforin, separated isocratically on a 12microm semiprep column, is obtained in high purity, lyophilized after the removal of the organic phase, and preserved at a low temperature. The purity of the collected marker compound is estimated by the use of LC-mass spectrometry and spectroscopic techniques.

Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.

A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.

A new glycoside, 3-O-demethylcolchicine-3-O-alpha-d-glucopyranoside, from Gloriosa superba seeds.

A new colchicine glycoside, 3-O-demethylcolchicine-3-O-alpha-D-glucopyranoside, has been isolated from Gloriosa superba seeds. The assigned structure has been corroborated by spectroscopic data and enzymatic hydrolysis.

Anti-inflammatory activity of the hydrosoluble fraction of Euphorbia royleana latex.

The hydrosoluble fraction of Euphorbia royleana latex (AER), administered by gavage at doses of 50-200 mg/kg, showed dose-dependent anti-inflammatory and anti-arthritic effects in different acute and chronic test models in rats and mice. It reduced the exudate volume and the migration of leukocytes and showed a poor inhibitory effect on the granuloma formation induced by cotton pellets, while it had a low ulcerogenic score. The oral LD(50) was more than 1500 mg/kg in both rats and mice.

Effect of plumbagin on gonadotrophic cycle of the housefly, Musca domestica L.

Topical treatment of the phytochemical plumbagin in doses ranging 0.005-5 micrograms prevented oocyte development and affected fecundity and fertility in M. domestica. The treatment to wandering larvae was less effective as the compound could only effect the fertility to a significant level whereas the fecundity was not significantly reduced. The effect of the compound was more pronounced in adult treatments where both fecundity and fertility reduced drastically. The compound also effected the oocyte maturation as it arrested the development of vitellogenic oocyte at stage six. As the juvenile hormone analogue methoprene and moulting hormone 20-hydroxyecdysone or the mixture of these hormones could not restore the development of the oocyte in ovaries of plumbagin treated flies, it is concluded that the compound does not effect the female houseflies through hormonal pathways, instead in all probability it acts like a cytotoxic compound.

Hypotensive activity of 8,24-euphadien-3 beta-ol (euphol).

8,24-Euphadien-3 beta-ol (euphol) on i.v. administration was found to exhibit a hypotensive activity in normotensive anesthetised dogs and rats which varied from a slight to a marked degree depending upon the dose range. Euphol inhibited various autonomic pressor and depressor responses. The hypotensive effect was not affected in dogs pretreated with atropine, antistine, and beta-blockers and in bilaterally vagotomised and carotid sinus denervated animals. The fall in blood pressure was enhanced in spinal transected and eviscerated dogs and after ganglion blockade with hexamethonium. Localisation of euphol to central cardiovascular loci displayed no effect on blood pressure. The LD50 in mice was found to be 1500 mg/kg i.p. and greater than 2 g/kg by the oral route.