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Jeyaseeli L.,Jadavpur University | Dasgupta A.,Jadavpur University | Dasgupta A.,U.S. National Institute on Aging | Dastidar S.G.,Herbicure Healthcare Bio Herbal Research Foundation | And 2 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2012

Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p<0.01) was observed when Fp was combined with Pc following the disc diffusion assay system. With the help of the checkerboard method, the fractional inhibitory concentration (FIC) index of this pair was found to be 0.375, confirming synergism. This pair of Fp+ Pc was then subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74. Statistical analysis of the mouse protection test suggested that this combination was highly synergistic (p<0.001, Chi-squared analysis). Fp also revealed augmentation of its antimicrobial property when combined with streptomycin, gentamicin, ciprofloxacin, and the non-antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp. © Springer-Verlag 2011.


Dasgupta A.,Herbicure Healthcare Bio herbal Research Foundation | Dasgupta A.,U.S. National Institute on Aging | Dastidar S.G.,Herbicure Healthcare Bio herbal Research Foundation
Indian Journal of Medical Research | Year: 2012

Background & objectives: Vibrio cholerae produces acute infection by liberating potent enterotoxin, called cholera toxin in human intestine. Cardiovascular drug lacidipine possessing powerful in vitro action against V. cholerae was tested to determine its possible activity against a toxigenic V. cholerae strain in an established animal model. Methods: In the rabbit intestine four loops were constructed, 3 of which were injected with over night grown V. cholerae 569B culture. Of these, two loops were simultaneously given graded doses (100, 200 μg) of lacidipine, one was left as such for a positive control. The first loop received sterile medium (negative control). After 18 h, contents of all the loops were examined for accumulation of fluid and number of viable cells. Results: Lacidipine when administrated with live V. cholerae 569B, caused a reduction in the number of viable bacteria along with amount of fluid in the loops. The amount of fluid and number of viable cells were much reduced in the loop that had 200 μg of lacidipine than the loop that received 100 μg of the drug. Interpretation & conclusions: Lacidipine has distinct inhibitory action against V. cholerae 569B with respect to both viability and production of cholera toxin in the rabbit ileum. Structural modifications of this compound may possibly lead to procurement of new potent antimicrobial drugs.


Dasgupta A.,Herbicure Healthcare Bio Herbal Research Foundation | Dasgupta A.,U.S. National Institute on Aging | Chaki S.,Herbicure Healthcare Bio Herbal Research Foundation | Mukherjee S.,Herbicure Healthcare Bio Herbal Research Foundation | And 4 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2010

The cardiovascular drug lacidipine (Lc) is known to possess antibacterial activity. Further potentiation of action is possible by synergism between Lc and an antibiotic or a non-antibiotic. The minimum inhibitory concentration (MIC) of antibiotics, Lc and other non-antibiotics were detected by the agar dilution technique in different bacteria. Synergism was determined by disc diffusion assay, the fractional inhibitory concentration (FIC) index through checkerboard assessment and, also, the protective capacity of the combination by administering the drugs along with 50 × LD50 challenge dose of virulent Salmonella typhimurium in animal experiments. Synergism between Lc and penicillin was found to be statistically significant (P∈≤∈0.01) when compared with their individual effects. The FIC index of this combination was 0.375, confirming synergism. In vivo tests suggested the statistically significant protection of infected mice with this combination. Lc exhibited synergism when combined with non-antibiotics methdilazine and triflupromazine both in vitro and in vivo. Distinct antimicrobial action of Lc and its subsequent synergism with other drugs can open up the possibility of synthesising new molecules by the structural analyses of these compounds. © 2009 Springer-Verlag.


Christensen J.B.,Copenhagen University | Hendricks O.,University of Southern Denmark | Chaki S.,Herbicure Healthcare Bio Herbal Research Foundation | Mukherjee S.,Herbicure Healthcare Bio Herbal Research Foundation | And 4 more authors.
PLoS ONE | Year: 2013

A long list of chemotherapeutical drugs used in the treatment of the peripheral and the central nervous systems possess anti-microbial activity. Some of these neurotropic compounds are chiral, with the one stereo isomeric form exaggerating reduced neurotropism. This is the case for the levorotatory form of thioridazine. The phenothiazine thioridazine is an interesting compound, characterized by exhibiting a significant growth inhibiting activity on a wide array of micro-organisms. Thioridazine is characterized by another challenging feature, because the compound is concentrated in certain human tissue cells. The present study describes a comparative study of the two enantiomers as well as the racemic form of thioridazine. The study exploits the stereochemical aspect and the in vitro and in vivo potential of these compounds, with a focus on the effects on Gram negative organism Salmonella enterica serover Typhimurium. In summary, the results of this study yielded a significant antibacterial activity of all forms of thioridazine, indicating the levorotatory (-)- form to be superior in terms of both its in vitro and in vivo efficacies. © 2013 Christensen et al.


Sarkar A.K.,Jadavpur University | Ghosh D.,Jadavpur University | Haldar D.,Jadavpur University | Sarkar P.,Jadavpur University | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012

A rapid, simple, and sensitive high performance liquid chromatography-tandem mass spectrometry method (LC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of choline (CL), active metabolite of citicoline in human plasma using metformin (MF) as IS. The chromatographic separation was performed on a reversed-phase Phenomenx Gemini C18 column with a mobile phase of methanol:water (containing 10. mM ammonium formate) (9:1, v/v). The calibration curves were linear over the range of 0.05-5μg/ml. The validated LC-ESI-MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters and bioequivalence study of test and reference control release (CR) tablet preparation of citicoline 1000. mg after a single oral administration to all 12 healthy male volunteers. © 2012 Elsevier B.V.


Kristiansen J.E.,University of Southern Denmark | Dastidar S.G.,Herbicure Healthcare Bio Herbal Research Foundation | Palchoudhuri S.,Herbicure Healthcare Bio Herbal Research Foundation | Roy D.S.,Herbicure Healthcare Bio Herbal Research Foundation | And 3 more authors.
International Microbiology | Year: 2015

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (-) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (-) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease. © 2015, Sociedad Espanola de Microbiologia. All rights reserved.


Mukherjee S.,Herbicure Healthcare Bio Herbal Research Foundation | Chaki S.,Herbicure Healthcare Bio Herbal Research Foundation | Das S.,Jadavpur University | Sen S.,CSIR - Central Electrochemical Research Institute | And 2 more authors.
Indian Journal of Experimental Biology | Year: 2011

The dicarbonyl compound methylglyoxal is a natural constituent of Manuka honey produced from Manuka flowers in New Zealand. It is known to possess both anticancer and antibacterial activity. Such observations prompted to investigate the ability of methylglyoxal as a potent drug against multidrug resistant Pseudomonas aeruginosa. A total of 12 test P. aeruginosa strains isolated from various hospitals were tested for their resistances against many antibiotics, most of which are applied in the treatment of P. aeruginosa infections. Results revealed that the strains were resistant to many drugs at high levels, only piperacillin, carbenicillin, amikacin and ciprofloxacin showed resistances at comparatively lower levels. Following multiple experimentations it was observed that methylglyoxal was also antimicrobic against all the strains at comparable levels. Distinct and statistically significant synergism was observed between methylglyoxal and piperacillin by disc diffusion tests when compared with their individual effects. The fractional inhibitory concentration index of this combination evaluated by checkerboard analysis, was 0.5, which confirmed synergism between the pair. Synergism was also noted when methylglyoxal was combined with carbenicillin and amikacin.


PubMed | Jadavpur University, University of Southern Denmark, Copenhagen University and Herbicure Healthcare Bio Herbal Research Foundation
Type: Journal Article | Journal: International microbiology : the official journal of the Spanish Society for Microbiology | Year: 2015

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (-) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (-) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease.


Dasgupta A.,Herbicure Healthcare Bio Herbal Research Foundation | Mukherjee S.,Herbicure Healthcare Bio Herbal Research Foundation | Chaki S.,Herbicure Healthcare Bio Herbal Research Foundation | Dastidar S.G.,Herbicure Healthcare Bio Herbal Research Foundation | And 5 more authors.
International Journal of Antimicrobial Agents | Year: 2010

When administered to mice at doses of 100 μg/mouse and 200 μg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55 kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55 kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane. © 2009 Elsevier B.V. and the International Society of Chemotherapy.


Chatterjee M.,Nil Ratan Sircar Medical College | Bhattacharya S.,Nil Ratan Sircar Medical College | Karak K.,P.A. College | Dastidar S.G.,Herbicure Healthcare Bio Herbal Research Foundation
Indian Journal of Medical Research | Year: 2013

Background & objectives: There has been an extensive invasion of tuberculosis at the global level by multidrug resistant as well as extensively drug resistant organisms. Attempts to recover the pathogen in pure culture have frequently failed since the specimens are often highly contaminated and also due to use of insufficient or over-active decontamination procedures. Hence in the present study different methods of decontamination were tested to evaluate their independent efficacies for culture of Mycobacterium tuberculosis. Methods: A total of 359 samples (241 sputum, 59 urine, 50 endometrium biopsy, 9 pus samples) from clinically suspected cases of tuberculosis were subjected to four different methods of decontamination followed by inoculation in Lowenstein-Jensen medium (LJM), and bilayered medium (BLM) and Kirchner's liquid medium (KLM) to determine the influence of differential decontamination processes. Sputum scanty and positive specimens were graded and each sample was subjected to decontamination by four different techniques. Results: Treatment of specimens with 4 per cent NaOH yielded minimum recovery of pure cultures, while use of 2 per cent NaOH produced higher number of contaminants compared to other methods of decontamination. Addition of N-acetyl L-cystein (NALC) coupled with 2 per cent NaOH to the samples for decontamination provided fairly reasonable recovery, but the highest number of M. tuberculosis cultures could be obtained when the specimens were treated with tri-sodium phosphate and benzalkonium (TSPB). Among the sputum positive cases recovery of growth of M. tuberculosis was higher with greater number of bacilli present in the specimens. Regarding the influence of culture media, BLM produced not only rapid growth, but reasonably higher rate of isolation of M. tuberculosis. Interpretation & conclusions: Although use of TSPB was found to be an efficient method of decontamination for successful isolation of M. tuberculosis from contaminated samples, both NALC+ 2 per cent NaOH and TSPB also showed significant recovery of M. tuberculosis cultures in BLM that can facilitate early diagnosis and initiation of treatment.

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