Showing papers by "Central Drug Research Institute published in 2004"
TL;DR: The results suggest the identification of a structural element in melittin, which probably plays a prominent role in regulating its toxicity but not antibacterial activity, and indicates that cell selectivity in some antimicrobial peptides can probably be introduced by modulating their assembly in an aqueous environment.
200 citations
TL;DR: Among them compounds 5a, g, m, o, p and r showed significant reduction in blood glucose levels in both SLM and STZ animal models.
190 citations
TL;DR: Staining with 0.05% TTC provided improved delineation of brain infarcts, reduced 'nonspecific' staining of white matter and the infarCT size correlated well with that measured after 1% TTC staining; the method also reduces the costs to 1/20.
158 citations
TL;DR: In vivo anti-malarial sensitivity test of this compound on Swiss Albino mice with Plasmodium berghei infection using Peters' 4-day test gave substantial reduction in parasitaemia after treating the mice with 30 mg kg(-1) dose.
153 citations
TL;DR: OS was found to possess potent anti-ulcerogenic as well as ulcer-healing properties and could act as a potent therapeutic agent against peptic ulcer disease.
120 citations
TL;DR: In this article, an efficient and eco-friendly synthesis of glycosyl 1,4-dihydropyridines has been achieved by a three-component reaction of β-keto esters or ketones, enamines and glycoly aldehydes in the presence of tetrabutylammonium hydrogen sulfate as catalyst in diethylene glycol.
119 citations
TL;DR: The strategy to conveniently synthesize naturally occurring chromeno dihydrochalcones by biogenetic type pyridine or Amberlyst-15 catalyzed chromenylation of dihydropyranes and in vitro antileishmanial activity of chromenoDihydro Chalcones and their intermediates is reported.
117 citations
TL;DR: Five new flavonoid C-glucosides, isolated from an aqueous extract of the heartwood of Pterocarpus marsupium, were isolated and the structure has been established using spectroscopic data.
103 citations
TL;DR: Oral co-administration of methylene blue appears to result in a small reduction of chloroquine exposure which is not expected to be clinically relevant and thus represents no concern for further development as an anti-malarial combination.
Abstract: Objective
The combination of chloroquine and methylene blue is potentially effective for the treatment of chloroquine-resistant malaria caused by Plasmodium falciparum. The aim of this study was to investigate whether methylene blue influences the pharmacokinetics of chloroquine.
88 citations
TL;DR: Fruits of Pongamia pinnata afforded four new furanoflavonoids, pongapinnol A-D, and a new coumestan, pONGacoumestans, along with thirteen known compounds 6-18, which are isolated for the first time from this plant.
83 citations
TL;DR: Current available literature is still not sufficient to validate the prophylactic/therapeutic efficacy of l-arginine and its metabolites, NO and agmatine, which hold the key for future research in cardiovascular system.
TL;DR: The present review has been planned to provide an account of the investigations carried out on traditional/folkloric plants used for fertility regulation and the status of scientific validations of their anti-fertility potential and identification of active principles during the last 28 years are discussed.
Abstract: Plants have been used worldwide for treatment of various human ailments since antiquity. Their use is still quite prevalent in developing countries in the form of traditional/folkloric system of medicine. Intensive chemical and pharmacological studies on traditional/folkloric medicinal plants during the last 5 decades have led to the validation of traditional claims in many cases and facilitated identification of their active principles. The active principles have provided leads in the development of several life saving drugs, which are in clinical use today. A large number of these plants are used for birth control in different countries. The present review has, therefore, been planned to provide an account of the investigations carried out on traditional/folkloric plants used for fertility regulation. The status of scientific validations of their anti-fertility potential and identification of active principles during the last 28 years are discussed. The literature survey shows that approximately 318 different plants are in traditional/folkloric use worldwide, of which 227 plants are of Indian origin. So far, 74 plants have been screened for their anti-fertility potential, 48 of them have been found to be effective. Active principles of about 15 plants have been identified during the period under review.
TL;DR: Results clearly indicate that Leishmania contains a novel form of actin which may structurally and functionally differ from other eukaryotic actins.
TL;DR: Three of the test compounds, 2-methyl-4,5-diphenyl-3-substituted-phenyl-1H-pyrroles (3c, d and h) showed significant inhibition on postprandial hyperglycemia in normal rats post sucrose loaded.
TL;DR: The role of ascorbate in the modulation of NO‐mediated ROS generation from PMNs is delineated and it is indicated that inhibitors of DHA uptake, reduced nicotinamide adenine dinucleotide phosphate oxidase, NO synthase, or ROS scavengers attenuated ROS generation.
Abstract: Recent studies from our laboratory have demonstrated that ascorbate potentiated enzymatic synthesis of nitric oxide (NO) from polymorphonuclear leukocytes (PMNs). NO is known to modulate various function of PMNs such as chemotaxis, adherence, aggregation, and generation of reactive oxygen species (ROS). The role of ascorbate in the PMN phagocytosis, ROS generation, and apoptosis was thus evaluated in the present study. Ascorbate and its oxidized and cell-permeable analog, dehydroascorbate (DHA), did not affect the phagocytosis but enhanced ROS generation and apoptosis following treatment with Escherichia coli or arachidonic acid. A detailed investigation on the DHA-mediated response indicated that inhibitors of DHA uptake, reduced nicotinamide adenine dinucleotide phosphate oxidase, NO synthase, or ROS scavengers attenuated ROS generation. In DHA-treated cells, enhanced generation of peroxynitrite was also observed; thus, ascorbate-mediated ROS and reactive nitrogen species generation might mediate cytotoxicity toward the ingested microbes and subsequently, augmented PMN apoptosis. Results of the present study have helped in delineating the role of ascorbate in the modulation of NO-mediated ROS generation from PMNs.
TL;DR: There is some interaction between these mycotoxins that resulted in reduced teratogenic activity of OA in the presence of AFB1, and apparently, new manifestations observed in combination treatment points to the potential threat of teratogenicity in terms of public health hazards.
Abstract: Ochratoxin A (OA) and Aflatoxin B1 (AFB1), the food borne mycotoxins are produced by several fungal species of the genera Aspergillus and Penicillium. To determine the teratogenic effects, these mycotoxins were administered orally either individually or in combination to the pregnant Wistar rats on days 6–15 of gestation. OA and AFB1 were dissolved in corn oil and different doses of OA (0.125, 0.25, 0.50, and 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, and 1.00 mg/kg), and a combination of OA+AFB1 (0.125+0.125; 0.25+0.50; 0.50+0.25 mg/kg) were given by gastric intubation to rats. During dosing period, the body weight and body weight gains significantly decreased at a higher dosage, in both individual and combined treatments. In all the combination treatments, the percent implants resorbed, fetal body weights, and crown-rump lengths were comparable to those of controls and with the individual mycotoxin treatment. The number of dead fetuses was significantly increased in the high OA combination (OA+AFB1 0.50+0.25) group as compared with the other two combinations. OA and AFB1 alone and in combination caused various gross, skeletal, and visceral anomalies. The occurrence was considerably less pronounced in fetuses of AFB1 and combination groups as compared with those of OA group fetuses. The exencephaly, incomplete closure of skull, wavy and fused ribs, agenesis of the ischium bone, and enlarged renal pelvis, recorded in OA treatment and ear abnormality and incomplete ossification of skull bones observed in AFB1 when given individually, were not seen in combination groups. However, new manifestations, such as gastroschisis and syndactyly were observed and the incidence of cardiac defects was increased in fetuses due to the combined treatment. The results of the present study indicated that there is some interaction between these mycotoxins that resulted in reduced teratogenic activity of OA in the presence of AFB1. Apparently, new manifestations observed in combination treatment points to the potential threat of teratogenicity in terms of public health hazards. Birth Defects Res B 71:343–351, 2004. © 2004 Wiley-Liss, Inc.
TL;DR: Some new tricyclic molecules bridged between the active molecules of 3,4-Diaryl chroman and 2,3-diaryl benzopyrans have been synthesised to search for newer oestrogen agonists or antagonists.
TL;DR: In this article, the authors demonstrated that full-length calcitonin is the sole constituent of amyloid in MTC and showed that it can be detected by measuring fold enhancement of thioflavin T fluorescence.
Abstract: Medullary thyroid carcinoma (MTC) is associated with amyloid deposition in the surrounding tissues. MTC-positive tumor thyroid tissues surgically removed from patients were used in our study to extract amyloid. We tested the MTC extracts for the presence of amyloid by measuring fold enhancement of thioflavin T fluorescence. Transmission electron microscopic study and atomic force microscopy of MTC patient extracts revealed typical amyloid fibrils. Matrix-assisted laser desorption ionization-time of flight mass spectrometric analysis demonstrated full-length calcitonin as the constituent of the MTC amyloid from seven patients. Our results unequivocally demonstrated that full-length calcitonin is the sole constituent of amyloid in MTC.
TL;DR: Using green fluorescent protein (GFP), a GFP marker is introduced into field strains of Leishmania causing kala-azar and the suitability of transgenic L. donovani promastigotes that constitutively express GFP in their cytoplasm as target cells for in vitro screening of anti-leishmanial drugs is explored.
Abstract: Classic techniques for detecting the susceptibility of Leishmania to different drugs are time-consuming, laborious, and require the use of macrophages. The use of flow cytometry for monitoring Leishmania susceptibility to drugs is beginning to be implemented. Using green fluorescent protein (GFP), we have improved and simplified the screening procedure. We introduced a GFP marker into field strains of Leishmania causing kala-azar (visceral leishmaniasis) and explored the suitability of transgenic L. donovani promastigotes that constitutively express GFP in their cytoplasm as target cells for in vitro screening of anti-leishmanial drugs.
TL;DR: A new series of diaryloxy methano phenanthrenes prepared through tertiary-aminoalkylations of [(methoxy-phenyl)-phenanthren-9-yl-methyl]-phenols obtained from Friedel-Crafts alkylations showed the desired activity in the range of 6.25 microg/mL in vitro and in vivo.
TL;DR: The study suggests that thiazolidinones with 3-(pyridin-2-yl) moiety provide scope for further substituent variation to modulate the HIV-1 RT inhibitory activity.
Abstract: A detailed structure-activity relationship study of the HIV1 Reverse Transcriptase (RT) inhibitory activity of two series of compounds, 2-(2,6-dihalo phenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones and 2-(2,6-Dihalophenyl)3-(substituted phenyl)-thiazolidin-4-ones, belonging to 2,3diaryl-thiazolidin-4-ones in terms of physicochemical and structural descriptors have been carried out using combinatorial protocol interfaced multiple linear regression (CP-MLR) and partial least squares (PLS) analysis. The models developed in the study indicate a preference for hydrophobic compounds for better inhibitory activity. Also, a positive regression coefficient of I2,3, an indicator descriptor meant for the joint disposition of substituents of 2,3-diaryl moieties of thiazolidinones to address their ability in taking a butterfly like conformation, is in agreement with all earlier observations that compounds having the ability to take butterfly like conformation will be showing better inhibitory activity. The identified models suggest that the meta-positions of 3-aryl moiety has the ability to accommodate hydrophobic/ steric groups. The replacement of C2 of 3-phenyl by nitrogen resulted in 3-pyridyl variants of these analogues. Even though from geometry point of view, the phenyls and pyridyls span almost the same structural space and steric features, presence of nitrogen in pyridyls gave them a blend of polarity, electronic features and a different hydrophobicity profile when compared to corresponding phenyl analogue. Furthermore the PLS models, developed from those descriptors took part in CP-MLR models, indicate that most of the descriptors have almost equal influence in accounting for the variation in the activity of these compounds. This suggests that the factors responsible for the variation in the activity have been uniformly distributed across the varying centers of the molecule. The study suggests that thiazolidinones with 3-(pyridin-2-yl) moiety provide scope for further substituent variation to modulate the HIV-1 RT inhibitory activity.
TL;DR: Dicitrate salts of these trioxaquines have been evaluated for antimalarial activity against multidrug resistant Plasmodium yoelii in mice model.
Journal Article•
TL;DR: Impaired consciousness, high total leukocyte count, raised ESR, elevated creatinine and SGPT levels, estimated within 24 hours of hospitalization, are the most important indicators of 30-day mortality in patients with first-time ischemic stroke.
Abstract: OBJECTIVE: This prospective study was planned to study the prognostic value of routine clinical, hematological and biochemical parameters, including platelet aggregation in patients of acute stroke, on fatality occurring during the first 30 days. MATERIAL AND METHODS: In this study 116 consecutive patients (77 males and 39 females) of stroke (within 72 hours of onset) were included. After clinical evaluation and neuroimaging, blood investigations, hemoglobin, total leukocyte count, platelet count, platelet aggregation, erythrocyte sedimentation rate (ESR), blood sugar, urea, creatinine, sodium, potassium, serum cholesterol, serum bilirubin, aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), albumin, and globulin estimations were performed. The patients were followed up for a maximum period of 30 days from the onset of stroke, and patients who expired were grouped as 'expired' and the rest as 'survivors'. Logistic regression analysis was carried out among the significant parameters to identify independent predictors of 30-day fatality. RESULTS: Univariate analysis demonstrated that among hematological parameters, high total leukocyte count and ESR, at admission, correlated significantly with an undesirable outcome during the initial 30 days. Among biochemical parameters, elevated urea, creatinine, serum transaminases (SGOT and SGPT) and globulin levels correlated significantly with death. Logistic regression analysis demonstrated that a low Glasgow Coma Scale (GCS) score along with biochemical parameters such as high serum creatinine, SGPT, ESR and total leukocyte count correlated with death. CONCLUSION: Impaired consciousness, high total leukocyte count, raised ESR, elevated creatinine and SGPT levels, estimated within 24 hours of hospitalization, are the most important indicators of 30-day mortality in patients with first-time ischemic stroke.
TL;DR: The present study indicates that the occurrence of brain, kidney, and liver lesions in combination treatment was less than in either individual treatment suggesting antagonism of OA-induced teratogenic effects by AFB1.
Abstract: The histopathological features of various abnormalities induced by different doses of ochratoxin A (OA), aflatoxin B1 (AFB1), and their combination in rat fetuses were studied. The pregnant Wistar rats were orally treated during 6–15 gestation days with different doses of OA (0.125, 0.25, 0.50, 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, 1.00 mg/kg), and their combination (0.125+0.125, 0.25+0.50, 0.50+0.25 mg/kg). The fetal sections passing through liver, kidney, brain, heart, and eyes were selected from the fetuses given visceral examination representing each litter. The selected sections were processed for paraffin embedding, stained with H and E, and examined by light microscopy. The histological examination of the fetal organs revealed that OA, AFB1, and their combination treatments caused variable changes in internal organs. In the case of OA, the incidence of pathological lesions liver, kidney, brain, and eye lesions was high, whereas in AFB1treatment, liver, brain, kidney, and heart were affected. The incidence of heart lesions, especially valvular defects, increased in the combination groups. Bile duct proliferation/new bile duct formation, defective ossification of cranial bones, exposure of the brain to the exterior, hypoplasia of cerebellum, and retinal defects observed in OA treatment and spinal cord defects in addition to liver, kidney, and brain changes observed in AFB1 were less severe in the combination groups. The present study indicates that the occurrence of brain, kidney, and liver lesions in combination treatment was less than in either individual treatment suggesting antagonism of OA-induced teratogenic effects by AFB1. The indication of subtle lesions due to an interference with normal development and arrest of differentiation in various internal organs observed in the present study suggests that microscopic examination of the tissues can provide additional useful information to a developmental toxicity study. Birth Defects Res B 71:352–358, 2004. © 2004 Wiley-Liss, Inc.
TL;DR: Modulation of AMPA receptor by different mechanisms has been discussed in the present review to implicate importance of these targets/pathways for safer and future neuro-protective drugs.
Abstract: The post-synaptic AMPA receptors play an important role in mediating fast excitatory transmission in the mammalian brain. Over-activated AMPA receptors induce excitotoxicity, implicated in a number of Chronic neurodegenerative disorders such as Parkinson's disease, Huntington's disease, and AIDS encephalitis. AMPA receptor antagonists offer protection against neurodegeneration in the experimental models even if they are given 24 h after the injury. Because AMPA receptors seem to be involved in the neurodegenerative diseases, modulating the activity of the AMPA receptors could be an attractive approach to reduce or prevent excitotoxicity. Studies conducted recently have exhibited a number of new mechanisms for AMPA receptor regulation. Modulations of these were found to have protective implications. AMPA receptor depolarization and desensitization are protective to the neurons. Receptor desensitization depends on the receptor subunit composition. The R/G editing site and the flip/flop cassettes in AMPA receptor subunits contribute to a great extent in receptor desensitization and recovery rates. Molecules that could quicken receptor desensitization or delay recovery could be of use. AMPA receptors limit neuronal entry of Ca2+ ions by regulating Ca2+-permeability. Ca2+-permeable receptor channels are made up of GluR1, GluR3, or GluR4 subunits, whereas presence of the GluR2 subunit restricts Ca2+ entry and renders the receptor Ca2+-impermeable. GluR2 levels, however, experience a fall after neuronal insult rendering the AMPA receptors Ca2+-permeable, thus factors that could interfere with this event might prove to be very beneficial against excitotoxicity. AMPA receptor clusters are stabilized by PSD-95, which requires palmitoylation at two sites. Targeting palmitoylation of the PSD-95 can also be a useful approach to disperse AMPA clusters at the synapse. In the perisynaptic region, mGluRs are present a little away from the synapse and are among the glutamate transporters, which require high-frequency firing for activation. On activation they might enhance the activity of NMDA receptors at the synapse to increase the levels of AMPA receptors. AMPA receptors surfaced at this juncture can contribute to heavy Ca2+ influx. Thus, blocking this pathway could be of considerable importance in preventing the excitotoxicity. A number of proteins such as the GRIP, PICK, and NSF also modulate the functions of AMPA receptors. Polyamines also block Ca2+ permeable AMPA receptors and thus are protective. NO and cGMP also play an important role in negatively regulating AMPA receptors and thus could offer protection. Modulation of AMPA receptor by different mechanisms has been discussed in the present review to implicate importance of these targets/pathways for safer and future neuroprotective drugs.
TL;DR: In this article, a 3-component condensation of isotoic anhydride, amine, and aldehyde in presence of iodine was used to obtain a moderate to good yield.
TL;DR: Antimalarial activity of amino functionalized trioxane 9a, the most potent compound in the series, is very close to that of beta-arteether.
TL;DR: In this paper, 4-thiazolidinones have been assembled by HBTU mediated three-component reaction of amine, aldehyde and mercapto acid derivatives at room temperature.
Abstract: In the present study, 4-thiazolidinones have been assembled by HBTU mediated three-component reaction of amine, aldehyde and mercapto acid derivatives at room temperature. The final compounds are o...
TL;DR: T. arjuna fractions at tested concentrations inhibited the oxidative degradation of lipids in human low density lipoprotein and rat liver microsomes induced by metal ions and counteracted the formation of superoxide anions and hydrodyl radicals in non enzymic test systems.
Abstract: Terminalia arjuna (T. arjuna) stem bark was successively extracted with petroleum ether (A), solvent ether (B), ethanol (C) and water (D). The lipid lowering activity of these four fractions A, B, C, and D was evaluatedin vivo in two models viz., triton WR-1339 induced hyperlipemia in rats as well as fructose rich high fat diet (HFD) fed diabetic- dyslipidemic hamsters. Hyperlipidemia induced by triton caused marked increase in the plasma levels of total cholesterol (Tc), triglyceride (Tg) and phospholipids (PL) in rats. After treament withT. arjuna fractions A, B, C, and D at the doses of 250 mg/kg per oral (p.o.),only the ethanolic fraction (C) exerted significant lipid lowering effect as assessed by reversal of plasma levels of Tc, Tg and PL in hyperlipidemic rats. In another experiment, feeding with HFD produced marked dyslipidemia as observed by increased levels of plasma Tc, Tg, glucose (Glu), glycerol (Gly) and free fatty acids (FFA) in hamsters. After treatment withT. arjuna fractions at the doses of 250 mg/kg p.o. only two fraction (B and C) could exert significant lowering in the plasma levels of lipids and Glu. in dyslipidemic hamsters.In vitro experimentT. arjuna fractions at tested concentrations (50–500 μg/ml) inhibited the oxidative degradation of lipids in human low density lipoprotein and rat liver microsomes induced by metal ions. These fractions when tested against generation of oxygen free radicals at the concentrations (50–500 μg/ml), counteracted the formation of superoxide anions (O−2) and hydrodyl radicals (OH) in non enzymic test systems. The efficacy ofT. arjuna fractions as antidyslipidemic and antioxidant agents was found, fraction C> fraction B> fraction A.
TL;DR: A number of thiazolidine-2,4-diones derivatives as well as their corresponding carboxylic acid showed significant improvement on post-prandial hyperglycemia in normal rats, in contrast to their poor agonist activity at PPARgamma.