Showing papers by "Central Drug Research Institute published in 2000"
TL;DR: Products of certain plants given to mothers after child birth or to invalids were studied for immunostimulant activity and feeding of Prunus amygdalus and Buchanania lanzan significantly stimulated both CMI and humoral immunity in BALB/c mice as evidenced by the enhancement of MMI, HA titres, and PFC counts.
155 citations
TL;DR: T tuftsin-bearing liposomes are designed and developed as drug carriers for the treatment of macrophage-based infections and outline these studies in this overview.
129 citations
TL;DR: Some of the screened compounds, 3a, 4c, 4e, 4f and 4i, have shown significant activity at 100 mg/kg dose against sensitive strain of Plasmodium berghei.
124 citations
TL;DR: It is suggested that curcumin could be used as a safe and effective drug in the treatment of idiopathic inflammatory orbital pseudotumours.
Abstract: The present report, describes for the first time the clinical efficacy of curcumin, the active constituent of rhizomes of Curcuma longa, in the treatment of patients suffering from idiopathic inflammatory orbital pseudotumours. Curcumin was administered orally at a dose of 375 mg/3 times/day orally for a period of 6-22 months in eight patients. They were followed up for a period of 2 years at 3 monthly intervals. Five patients completed the study, out of which four recovered completely and in one patient the swelling regressed completely but some limitation of movement persisted. No side effect was noted in any patient and there was no recurrence. It is suggested that curcumin could be used as a safe and effective drug in the treatment of idiopathic inflammatory orbital pseudotumours.
98 citations
TL;DR: The results suggest the effective use of an in vitro test system as an alternative for in vivo assessment of hepatoprotective activity of purified material.
Abstract: Ursolic acid is the active material isolated from the leaves of the Eucalyptus hybrid E. tereticornis. In the present study, it has shown a significant preventive effect in vitro against ethanol-induced toxicity in isolated rat hepatocytes. Compared with the incubation of isolated hepatocytes with ethanol only, the simultaneous presence of ursolic acid in the cell suspension preserved the viability of hepatocytes and reversed the ethanol-induced loss in the level of all the marker enzymes (AST, ALT and AP) studied. Ethanol alone resulted in a 48%-54% decrease in the viability and a 42%-54% reduction in the biochemical parameters of the hepatocytes. Ursolic acid showed a concentration dependent (1-100 microg/mL) preventive effect (12%-76%) on alcohol-induced hepatocyte toxicity by restoring the altered parameters. The results thus suggest the effective use of an in vitro test system as an alternative for in vivo assessment of hepatoprotective activity of purified material.
84 citations
TL;DR: The present review summarizes the modulatory role of NO on PMNs functions and points out the discrepancies relating to presence of NOS in PMNs.
79 citations
TL;DR: Comparison of the ED(90) values showed that azithromycin was 31-fold more effective than erythromycin as a blood schizontocide in the simian model, and in the causal prophylactic test, the prepatent period was significantly extended in monkeys challenged with P. cynomolgi B sporozoites, presumably because of the growth inhibition of preerythrocytic schizonts in hepatocytes.
72 citations
TL;DR: Various suitably functionalized pyrimidine derivatives have been synthesized to explore their potential as antimycotic agents and have shown highly significant in vitro antifungal activity against five human pathogenic fungi.
71 citations
TL;DR: It is shown that acute immobilization stress may enhance cognitive function in mice which may be attributed to a decrease in AChE activity leading to an increase in cholinergic activity in the brain.
70 citations
TL;DR: The syntheses of 7-chloro-4-(substituted amino) quinolines and their antifilarial activities are delineated and some of the screened compounds have shown promising filarial response and sterilization effect on female Acanthocheilonema viteae in rodents.
53 citations
TL;DR: The two most potent macrofilaricidal compounds, namely 4a and 4e, have been screened for their potency against DNA topoisomerase II, and it has been observed that both have the capability to interfere with this enzyme at 10 micromol/mL concentration.
Abstract: Quinolones have been discovered in our laboratory as a new class of antifilarial agents. This has led to the design, synthesis, and antifilarial evaluation of a number of N-substituted quinol-4(1H)-one-3-carboxamide derivatives 4-6. The macrofilaricidal activity of the target compounds was initially evaluated in vivo against Acanthoeilonema viteae by oral administration of 200 mg/kg x 5 days. Among all the synthesized compounds, 13 displayed activity, with the most potent compound (4a) exhibiting 100% macrofilaricidal and 90% microfilaricidal activities. Compound 4e elicited significant macrofilaricidal (80%) response while compound 5c showed 100% sterilization of female worms. Finally, the two most potent macrofilaricidal compounds, namely 4a and 4e, have been screened for their potency against DNA topoisomerase II, and it has been observed that both have the capability to interfere with this enzyme at 10 micromol/mL concentration. The structure-activity relationship (SAR) associated with position-3 and aryl ring substituents is discussed.
TL;DR: Results suggested that picroliv pretreatment protects rat kidneys from IRI, perhaps by modulation of free radical damage and adhesion molecules.
TL;DR: Picroliv pretreatment resulted in better hepatocyte glycogen preservation and reduced apoptosis, and enhanced proliferating cell nuclear antigen (PCNA) immunoreactivity, and these studies strongly suggest picroliv to be a promising agent for ameliorating injury following ischemia-reperfusion.
TL;DR: The structure of 2-methyl-6-methylthio-4-(3,4-methylenedioxyphenyl)benzonitrile (3f) was ascertained by single crystal X-ray diffraction analysis and displayed a variety of weak interactions as discussed by the authors.
Abstract: A convenient synthesis of highly functionalised biaryls 3 and 6 has been delineated through carbanion induced C–C bond formation from 6-aryl-3-cyano-4-substituted-2H-pyran-2-ones (1, 4) and acetone. Extension of this reaction, using aromatic ketones led to (4,6-diarylpyran-2-ylidene)acetonitrile (7) in lieu of the anticipated 2,4-diaryl-6-methylthiobenzonitrile (8). The structure of 2-methyl-6-methylthio-4-(3,4-methylenedioxyphenyl)benzonitrile (3f) was ascertained by single crystal X-ray diffraction analysis and displayed a variety of weak interactions, responsible for the stability and packing of the molecule in the crystalline state.
TL;DR: In vivo evidence is provided in support of the view that AcMNPV replication involves multipleori that are activated with vastly different efficiencies during the viral infection cycle.
Abstract: The identification of potential baculovirus origins of replication (ori) has involved the generation and characterization of defective interfering particles that contain major genomic deletions yet retain their capability to replicate by testing the replication ability of transiently transfected plasmids carrying viral sequences in infected cells. So far, there has not been any evidence to demonstrate the actual utilization of these putative origins in Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) replication. By using the method of origin mapping by competitive PCR, we have obtained quantitative data for the ori activity of the HindIII-K region and the ie-1 promoter sequence in AcMNPV. We also provide evidence for differential activity of the two ori in the context of the viral genome through the replication phase of viral infection. Comparison of the number of molecules representing the HindIII-K and ie-1 origins vis-a `-vis the non-ori polH region in a size-selected nascent DNA preparation revealed that the HindIII-K ori is utilized ;14 times more efficiently than the ie-1 region during the late phase of infection. HindIII-K also remains the more active ori through the early and middle replication phases. Our results provide in vivo evidence in support of the view that AcMNPV replication involves multiple ori that are activated with vastly different efficiencies during the viral infection cycle. The prototype baculovirus, Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV), has a double-stranded, closed-circular genome of ;134 kb with a coding capacity of over 150 polypeptides (2). AcMNPV gene expression is temporally regulated in an ordered cascade through early, late, and very late phases. Viral DNA replication precedes the late phase and initiates late/very late gene expression that ultimately results in the production of progeny virus (23). Interspersed in the AcMNPV genome are nine homologous regions (hr) that are adenine-plus-thymine-rich sequences containing two to eight 30-bp imperfect palindromes with an EcoRI site as the palindrome core (except hr4C) (7, 15). hrs were initially postulated to function as viral origins of replication (ori) because of their symmetric location in the genome, palindromic structure, and high A1T content (4). Subsequent analysis of these sequences by transient replication assays supported this hypothesis (1), and a single palindrome with an intact core was shown to be sufficient for hr plasmid replication in AcMNPV-infected cells (9, 20). Non-hr ori have also been reported in AcMNPV. These include sequences within the HindIII-K region (84.9 to 87.3 m.u.) that are tandemly repeated in defective viral genomes (18). Sequences within the HindIII-K fragment also support plasmid replication in transient replication assays (13). Additionally, early promoter regions of the virus, including the ie-1 gene upstream region and 11 other early promoter regions, have been demonstrated to function as plasmid ori in these assays, suggesting that early viral promoter sequences can also function as putative AcMNPV ori (35). A number of virally encoded genes involved in DNA replication have also been identified. These include five essential (p143, ie-1, lef-1, lef-2, and lef-3) and five stimulatory (dnapol, p35, ie-2, lef-7, and pe-38) genes from AcMNPV (14, 21, 22).
TL;DR: The 100% inhibition of fertility in female rats and rabbits immunized with major maturation-dependent 116 kDa glycoprotein showed the significance of glycosylation changes in the maturation status of epididymal spermatozoa.
Abstract: Glycosylation is one of the important post-translational modifications of sperm plasma membrane proteins during the maturation of epididymal spermatozoa that results in the development of motility and fertilizing capability. The aim of the present study was to identify and characterize the maturation-dependent asparagine-linked (N-linked) and serine- and threonine-linked (O-linked) glycoproteins of the epididymal spermatozoa of rhesus monkeys. The presence of N- and O-linked glycoproteins was confirmed by treatment of sperm membranes with N-glycosidase F and O-glycosidase. The major maturation-dependent sperm membrane glycoproteins identified on blots of SDS-PAGE-fractionated proteins of purified sperm plasma membranes from five segments of epididymis, probed with biotinylated lectins and Vectastain-ABC reagent included O-linked 170, 150, 86 and 60/58 kDa glycoproteins; N-linked 68, 56, 48 and 38 kDa glycoproteins and N- and O-linked 116 kDa glycoprotein, all of which exhibited marked differences in the degree of glycosylation between immature and mature sperm surfaces. These glycoproteins can be used as markers of sperm maturation in the epididymis of rhesus monkeys, during the screening of antifertility agents acting at the epididymis, or may be developed as potential sperm antigens. The 100% inhibition of fertility in female rats and rabbits immunized with major maturation-dependent 116 kDa glycoprotein showed the significance of glycosylation changes in the maturation status of epididymal spermatozoa. This 116 kDa protein can be used as a marker parameter of sperm maturation in the rhesus monkey, which is often the preferred animal model for preclinical studies. These results will contribute to the identification of an appropriate animal model for the development of male contraceptives in humans.
TL;DR: It may be postulated that the mechanism of action of these compounds could be through activation of lecithin cholesterol acyltransferase, liver lipolytic activity, increased faecal bile acid secretion and inhibition of hepatic cholesterol biosynthesis.
TL;DR: Desmethyl isoencecalin and 5-hydroxy-6-acetyl- 2-hydroxymethyl-2-methyl chromene isolated from Blepharispermum subsessile rhizomes were shown to have antifeedant activity against larvae of Spilarctia obliqua and also antifungal activity against Candida albicans and Cryptococcus neoformans.
TL;DR: A novel isoxazole-based scaffold has been identified for the generation of combinatorial libraries using solid-phase methods and has been utilized to afford high value synthetic intermediates through Baylis–Hillman reaction, Wittig reaction, nitroaldol condensation, and imine and oxime formation.
TL;DR: This study investigated the application of a fast growing nonpathogenic M. aurum expressing firefly luciferase in rapid screening of antituberculosis compounds in vitro and in infected macrophages using bioluminescence assay, which can reliably be used in high throughput screening.
TL;DR: ESI MS studies indicated that the trichloroacetate anion has a greater affinity for cytochrome c compared to trifluoroacetateAnion, which might be the reason for the stabilization of the native-like folded intermediate during TCA-induced denaturation of cy tochrome c as compared to extensive unfolding observed in the presence of TFA.
TL;DR: In this article, six synthetic 2H-1-benzopyran-2-one derivatives (CDRI compounds # 1, 2, 3, 4, 5 and 6) were evaluated for filaricidal activity against Litomosoides carinii and Acanthocheilonema viteae infections in cotton rats (Sigmodon hispidus) and Mastomys coucha respectively.
TL;DR: The study advocates the suitability of proposed rodent model to shortlist potential resistance reversal agents for use in in vitro studies against chloroquine resistant P. falciparum isolates.
TL;DR: Extensive D labelling and (6)Li labelling experiments confirmed many of the ion structures proposed, although the CID spectra of the sodiated ions are generally weaker, although similar to those of the corresponding lithiated species.
Abstract: The effect of alkali metal and silver cationization on the collision-induced dissociation (CID) of loganin (1), epi-loganin (2) and ketologanin (3) is discussed. Their protonated molecular ions fragment mainly by glycosidic cleavages. The epimeric pairs (1 and 2) show differences in the abundances of the resulting fragment ions. Lithium cationization induces new dissociation pathways such as the retro-Diels-Alder (RDA) fragmentation followed by rearrangement. Unlike the dissociation of protonated molecular ions, the dissociation of lithiated molecules also provides lithiated sugar fragments. The CID of dilithiated molecules is substantially different from that of the monolithiated precursors. RDA reaction appears to be favoured by the presence of the additional lithium atom in the molecule. In addition, other ring cleavages are also induced. The abundances of the various fragment ions are different in the CID spectra of the epimeric pairs. Extensive D labelling and (6)Li labelling experiments confirmed many of the ion structures proposed. The CID spectra of the sodiated ions are generally weaker, although similar to those of the corresponding lithiated species. Higher alkali metal ion (K(+), Rb(+) and Cs(+)) adducts generated only the corresponding metal ions as products of CID. Similar fragmentations were also observed in the CID of the [M + Ag](+) ions of these compounds, the epimeric pairs showing characteristic differences in their CID behaviour. Copyright 2000 John Wiley & Sons, Ltd.
TL;DR: The concentration-time data of AA in rats was best described by a one-compartment model with equal first order absorption and apparent elimination rate constants, and it was concluded that entero-enteric circulation of AA did not contribute significantly to the in-situ absorption rates.
TL;DR: A significant reduction in the DSP rate per testis was indicated during the non‐breeding season in two species, along with a marked decline in the testis weight, however, the gametogenic capacity of seminiferous tubules did not appear to be markedly affected during non-breeding season.
Abstract: Daily sperm production (DSP) rate was estimated in adult male rhesus and bonnet monkeys to evaluate seasonal changes in the gametogenic activity of the testes. Three monkeys of each species were castrated during breeding and non-breeding seasons and DSP rate was estimated by enumerating the homogenization-resistant spermatid nuclei of steps 13 and 14. Results indicated a significant reduction in the DSP rate per testis during the non-breeding season in two species, along with a marked decline in the testis weight. However, the gametogenic capacity of seminiferous tubules did not appear to be markedly affected during non-breeding season, as the DSP rate per gram parenchyma of testis was only marginally reduced. The seasonal changes in DSP were much more pronounced in the rhesus than in the bonnet monkey. The feasibility of circanual rhythm in DSP of sub-human primates to form a baseline for the study of reproductive function in male is discussed.
TL;DR: The study presents simple, economical, less time-consuming methods for the evaluation of methemoglobin toxicity, in vitro and in vivo, without employing the conventional Beagle dog model.
TL;DR: The immunomodulatory effect of the bark of Albizzia lebbeck (Sirisha) was evaluated by studying humoral and cell mediated immune responses and the effect was comparable to the standard drug muramyl dipeptide (MDP).
Abstract: The immunomodulatory effect of the bark of Albizzia lebbeck (Sirisha) was evaluated by studying humoral and cell mediated immune responses. The hot aqueous extract and its butanolic fraction were administered once daily for one week in mice, immunised previously with sheep red blood cells (SRBC). At the dose levels tested (6.25, 12.5 and 25 mg/kg, p.o.), A. lebbeck treated mice developed higher serum antibody titres compared to the vehicle treated group and the effect was comparable to the standard drug muramyl dipeptide (MDP). Delayed type hypersensitivity response was suppressed in SRBC immunised mice treated with A. lebbeck extract. The macrophage migration index remained unaltered in both mice and rats. These results are discussed in the light of possible immunopotentiating effects of A. lebbeck.
Journal Article•
TL;DR: A brief review presents an update of the available information on polyenes, imidazole, triazoles, flucytosine, allylamines, echinocandins, nikkomycins, sordarins and immunomodulators.
Abstract: The rising incidence of fungal infections and the emergence of several fungi as opportunistic pathogens have reawakened interest in chemotherapeutic and prophylactic agents for mycoses. During the past decades significant advances have been made in the development of novel antifungal agents for treatment of systemic mycoses. This brief review presents an update of the available information on polyenes, imidazoles, triazoles, flucytosine, allylamines, echinocandins, nikkomycins, sordarins and immunomodulators. A reference has also been made to the work in antifungals done or in progress at the Central Drug Research Institute (CDRI), Lucknow. Currently, antifungals represent more than 6% of the total world market for anti-infective agents and with 20% annual expansion they are expected to cross the 15 billion US Dollars in value within a decade.
TL;DR: The effects of dopaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam‐dependent rats and physical dependence was developed by giving lorzepam admixed with food in the following dose schedules.
Abstract: 1. The effects of dopaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam-dependent rats. Physical dependence was developed by giving lorazepam admixed with food in the following dose schedules: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 mg/kg, daily for x days. 2. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. 3. During the withdrawal period, rats were divided into groups of 10 rats each. One group did not receive any drug and served as the control withdrawal groups. Three other groups received, separately, one of the following dopamimetic drugs: (i) 200 mg/kg per day, i.m., L-dihydroxyphenylalanine (DOPA; +50 mg/kg per day, i.m., carbidopa); (ii) 2 mg/kg per day, i.m., amphetamine; or (iii) 1 mg/kg per day, i.m., apomorphine. The remaining groups received one of the following dopamine antagonists: (i) 0.1 mg/kg per day, i.m., SCH 23390; (ii) 0.5 mg/kg per day, i.m., haloperidol; (iii) 0.5 mg/kg per day, i.m., centbutindol; and (iv) either 1 or 20 mg/kg per day, i.m., clozapine. 4. The withdrawal signs observed in the control group were hyperkinesia, hyperaggression and audiogenic seizures. 5. L-Dihydroxyphenylalanine (+ carbidopa), amphetamine and apomorphine potentiated hyperaggression and audiogenic seizures. The dopamine D2 receptor antagonists haloperidol, centbutindol and clozapine (at 20 mg/kg, i.m.) blocked all withdrawal signs. The D1 receptor antagonist SCH 23390 inhibited hyperkinesia and hyperaggression. The D4 receptor antagonist clozapine (at 1 mg/kg, i.m.) had no effect on any of the withdrawal signs. 6. It may be concluded that dopamine D2 receptors exert a dominant facilitatory influence, with partial contribution of D1 receptors, on the benzodiazepine withdrawal syndrome.