Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers.
Adverse drug reaction; banned drugs; drug safety; pharmacovigilance
Cytohesins are small guanine nucleotide exchange factors that stimulate ADP ribosylation factors, Ras-like GTPases, which control various cellular regulatory networks ranging from vesicle trafficking to integrin activation. A small molecule SecinH3 (1,2,4-triazole derivative) in an aptamer displacement assay as a pan-cytohesin Sec7-domain inhibitor was previously identified. Here a series of different SecinH3-analogues was designed and synthesised as potential cytohesin Sec7-domain inhibitors. All final synthesized compounds 6-8, 43-58 and their intermediates were confirmed by 1H NMR, 13C NMR and high resolution Mass. Preliminary biological screening of target compounds indictaed that some of the new synthesized secinH3 derivatives showed higher potency and promising activity more than secinH3 itself (unpublished results). Compund 9 and 10 were approximate equal to secinH3 activity as cytohesin antagonist activity. Furthermore compound 52 showed twice inhibition potency if compared to secinH3.
SecinH3; synthesis; 1,2,4-triazole; pipronyloyl moiety; cytohesin inhibitors
A series of novel N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimines (Fa-e) were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (H37Rv) strain by using alamar blue assay. The synthesized compounds were characterized based on IR, 1HMR and mass spectral analysis. The toxicity profile was predicted by organic chemistry portal, a web based application for predicting in silico absorption, distribution, metabolism, excretion and toxicity, and the novel derivatives under study did not show any toxicity issues. The mechanism of action of the titled derivatives was predicted by docking on the Mycobacterium tuberculosis Enoyl-ACP reductase enzyme. The docking study concluded that Fb and Fa possessed good binding energy indicating more prominent interaction towards the active sites NAD and TYR 158. The antitubercular studies showed that the both Fa and Fb possessed significant activity with the MIC as low as 3.125 μg/ml.
Enoyl-ACP reductase; 1,3,4-oxadiazole; in silico ADMET; molecular docking
A new stability-indicating high-performance liquid chromatographic method for simultaneous analysis of sitagliptin and simvastatin in pharmaceutical dosage form was developed and validated. The mobile phase consisted of methanol and water (70:30, v/v) with 0.2 % of n-heptane sulfonic acid adjusted to pH 3.0 with ortho phosphoric acid was used. Retentions of sitagliptin and simvastatin were 4.3 min and 30.4 min, respectively with a flow rate of 1 ml/min on C8 (Qualisil BDS, 250×4.6 mm, 5 μ). Eluents were detected at 253 nm using photodiode diode array detector. The linear regression analysis data for the linearity plot showed correlation coefficient values of 0.9998 and 0.9993 for sitagliptin and simvastatin, with respective concentration ranges of 20-150 μg/ml and 8-60 μg/ml. The relative standard deviation for inter-day precision was lower than 2.0%. The assay of sitagliptin and simvastatin was determined in tablet dosage form was found to be within limits. Both drugs were subjected to a variety of stress conditions such as acidic, basic, oxidation, photolytic, neutral and thermal stress in order to achieve adequate degradation. Results revealed that considerable degradation was found in all stress conditions except oxidative degradations. The method has proven specificity for stability indicating assay method.
Sitagliptin; simvastatin; reverse phase liquid chromatography
Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.
Curcumin; diclofenac; oral bioavailability; rheumatoid arthritis; drug conjugate
In the present investigation, a novel multifunctional co-processed superdisintegrants consisting of crospovidone and Kyron T-314 were fabricated by solvent evaporation method to develop melt-in-mouth tablets of metoclopramide hydrochloride with a view to enhance patient compliance by direct compression method. The simple physical blends and co-processed mixture of superdisintegrants were characterized for angle of repose, bulk density, tapped density, Carr's index, Hausner's ratio and compatibility studies by FTIR spectroscopy. Melt-in-mouth tablets of metoclopramide hydrochloride were prepared using the physical blends and co-processed mixture of superdisinterants and were evaluated for hardness, friability, in vitro disintegration time, in vitro dispersion time, wetting time, water absorption ratio, drug content, in vitro drug release and accelerated stability study at 40±2° temperature and 75±5% relative humidity. Among the tablets evaluated, formulation F-X prepared by adding co-processed superdisintegrants in ratio of 1:1 showed minimum in vitro dispersion time of 9.71±0.021 s, in vitro disintegration time of 5.70±0.117 s and higher amount of drug release of 99.695±0.29% at the end of 1 min. Formulation F-X was emerged as the overall best formulation based on drug release characteristics in pH 6.8 phosphate buffer compared with the tablets obtained from conventional method of manufacture as well as with marketed preparation. Analysis of drug release data indicated that formulation F-X followed first order kinetics. This study revealed that the co-processed mixture of superdisintegrants have excellent flow properties, high compressibility, render low disintegration time to tablets and have better binding properties as compared to physical blends of superdisintegrants. These materials can be a good substitute for inert superdisintegrants, which are normally used in tablet manufacturing.
Direct compression; co-processed superdisintegrants; solvent-evaporation; crospovidone; Kyron T-314; metoclopramide hydrochloride; wetting time
Glucokinase is classified in bacteria based upon having ATP binding site and ‘repressor/open reading frames of unknown function/sugar kinases’ motif, the sequence of glucokinase gene (JN645812) of Staphylococcus aureus ATCC12600 showed presence of ATP binding site and ‘repressor/open reading frames of unknown function/sugar kinases’ motif. We have earlier observed glucokinase of S. aureus has higher affinity towards the substrate compared to other bacterial glucokinase and under anaerobic condition with increased glucose concentration S. aureus exhibited higher rate of biofilm formation. To establish this, 3D structure of glucokinase was built using homology modeling method, the PROCHECK and ProSA-Web analysis indicated this built glucokinase structure was close to the crystal structure. This structure was superimposed with different bacterial glucokinase structures and from the root-mean-square deviation values, it is concluded that S. aureus glucokinase exhibited very close homology with Enterococcus faecalis and Clostridium difficle while with other bacteria it showed high degree of variations both in domain and nondomain regions. Glucose docking results indicated -12.3697 kcal/mol for S. aureus glucokinase compared with other bacterial glucokinase suggesting higher affinity of glucose which correlates with enzyme kinetics and higher rate of biofilm formation.
Biofilm; glucokinase; molecular docking; RMSD; ROK
Mucoadhesive microbeads of low methoxyl pectin were prepared, either alone or in combinations with hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, methyl cellulose and carbopol 934P, by ionotropic gelation. The influence of copolymers on mucoadhesivity, microbeads characteristics and in vitro drug release was investigated. Spherical microbeads with 78.69±0.59 to 85.84±0.78% drug entrapment and of a size of 791.90±4.58 to 960.88±4.61 μm were prepared. The concentration of cross linking agent affects the encapsulation efficiency of microbeads. Mucoadhesiveness of microbeads was dependent on the concentration of copolymers. The formulations exhibiteda pH-dependent release and followed diffusion-controlled first-order kinetics.
Pectin; hydroxypropyl methylcellulose; ionotropic gelation; mucoadhesion; microbeads
A high performance liquid chromatography method was established for simultaneously determining four bioactive components, salicin, liquiritin, paeonolum, and imperatorin in Fengshiding capsule, a widely used traditional Chinese medicine for treating rheumatic disease. The chromatographic separation was performed on a Shimadzu Shim-pack Stable Bond C18 column using gradient elution with methanol and water. The analytical method was validated through precision, repeatability and stability, and the relative standard deviation values were less than 3%, respectively. The recoveries of the four investigated compounds ranged from 95.80 to 101.21% with relative standard deviation values less than 3.2%. Then this proposed method was successfully applied to determine six batches of Fengshiding commercial products of capsule dosage form from two pharmaceutical factories. This study might provide a basis for quality control for this traditional Chinese medicine preparation.
Fengshiding capsule; salicin; liquiritin; paeonol; imperatorin; high performance liquid chromatography
A field experiment on the effect of time of harvesting on yield and quality of Melissa officinalis L. was conducted under the agroclimatic conditions of Doon valley, Uttarakhand in order to assess the performance of four harvesting times (H1-120 days, H2-140 days, H3-160 days and H4-180 days after planting). The fresh and dry herbage and oil yield of the aerial parts showed greater response in H3 i.e. harvesting at 160 days after planting, followed by H2 harvesting time. The quality of essential oil was evaluated using GC and GC-MS analysis. Geranial (24.53 %) and neral (18.80 %) were the major constituents found in the essential oil followed by trans-caryophyllene (7.70 %).
Melissa officinalis L.; harvesting times; fresh and dry herbage; essential oil; geranial
A simple, rapid and highly sensitive spectrophotometric method is developed for the determination of risperidone in tablet formulation. The method is based on the oxidation of drug using potassium permanganate in alkaline medium and excess potassium permanganate oxidizes 1,10-phenanthroline Fe(II). The measurement of decrease in absorbance of 1,10-phenanthroline Fe (II) was done at 415 nm. The beer's law is obeyed in the concentration range of 5.0 to 40.0 μg/ml and molar absorptivity is found to be 7.3932 × 104 l/mol/cm. The proposed method is well suited for the pharmaceutical formulations.
Risperidone; potassium permanganate; 1,10-phenanthroline Fe (II); oxidation; tablets; spectrophotometry
In this study, the ethanol extract of Cissampelos pareira has been evaluated. The extract was tested for analgesic properties using both hot plate and acetic acid-induced writhing methods. Antiinflammatory effect was investigated using two different doses of 250 and 500 mg/kg body weight on Evans rats by carrageenan-induced paw edema test. The antipyretic activity was evaluated using Brewer's yeast-induced pyrexia in Wistar rats. The phytochemical screening of the extract of Cissampelos pareira exhibited the presence of several phytochemical compounds including saponins, gums and carbohydrates, reducing sugars, alkaloids and terpenoids. Ethanol extract of Cissampelos pareira exhibited significant analgesic, antiinflammatory and antipyretic activity in a dose-dependent manner. The results obtained from these studies confirm its therapeutic value against diseases caused by various pain and fever.
Cissampelos pareira; analgesic; antioxidant; antiinflammatory; antipyretic; carrageenan-induced paw edema; yeast
The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05) enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating) activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency.
Enhancement; Neuromuscular; Cordyceps sinensis; antidepressant; mice
For the prevention of postoperative ocular infections prophylactic topical antibiotics are routinely used. Studies evaluating comparative difference between single dose versus multiple dose administration on aqueous humour concentration of moxifloxacin are lacking. This study compared the aqueous humour concentration of moxifloxacin following its topical administration in rabbit eyes with two dose regimens. Twelve albino rabbits were divided into two groups. In group-1, two drops were administered thrice (total six drops) at 2 min intervals, in both the eyes; in group-2, two drops of moxifloxacin were administered three times a day for three days and also two h before aqueous humour collection i.e. on fourth day. Mean aqueous humour concentrations were calculated and compared using Student's ‘t’ test and P<0.05 was considered significant. Moxifloxacin concentration in aqueous humour in group-1 was 23.79 μg/ml and in group-2 was 42.08 μg/ml. Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for most bacteria. Moxifloxacin concentration in aqueous humour with multiple instillations is significantly higher than single instillation (P<0.05), which is adequate to cover ciprofloxacin-resistant gram-negative bacteria. Repeated topical moxifloxacin administration achieved significantly higher aqueous humour concentrations than single administration.
Aqueous humour; MIC90; moxifloxacin; rabbiteye
Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions.
Heartleaf; antioxidant; hydroxyl radicals; hepatotoxicity; hyperlipidemia; carbon tetrachloride
The present study we investigated the hepatoprotective effects of Olea europaea fruit pulp extract against carbon tetrachloride-induced hepatic damage in experimental mice. Further we explored the antioxidant potential of the extract to substantiate the hepatoprotective properties. Biochemical parameters were analyzed in the serum of experimental mice using respective diagnostic kits. Antioxidant activities were measured following alkyl and hydroxyl radical scavenging assays. Compared with control groups, administration of the extract to carbon tetrachloride-treated mice significantly reduced the elevated serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. The carbon tetrachloride-treated morphological changes in hepatocyte architecture were also reversed by extract pretreatment. Further, the carbon tetrachloride-treated increased serum cholesterol levels such as triglyceride and low density/very low-density lipoprotein in the liver were reversed in acute and chronic carbon tetrachloride-treated mice. The extract was also found to significantly increase the serum level of high-density lipoproteins in carbon tetrachloride-treated mice. Furthermore, the extract showed significant in vitro antioxidant actions by scavenging the alkyl and hydroxyl free radicals, substantiating its use in hepatoprotection. The concentration of the extract necessary for 50% inhibition of alkyl and hydroxyl radicals was 72.41 and 52.24 μg/ml, respectively. In conclusion, data from our study suggest that Olea europaea fruit pulp extract could prevent carbon tetrachloride-treated acute and chronic liver degeneration and attenuated the lipid levels elevated by carbon tetrachloride. The hepatoprotective activity exhibited by Olea europaea extract might possibly be through its antioxidant defense mechanisms.
Olive fruit pulp; antioxidant; hepatotoxicity; carbon tetrachloride; free radicals
Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers.
Clopidogrel; pharmacogenomics; pharmacogenetics; bioequivalence; polymorphism; CYP2C19
Due to the increasing demand for new pharmaceuticals showing biological activity against pathogenic microorganisms, there is increasing search for new compounds with predicted biological activity. Variously substituted thioamide derivatives with 1.3 and 1.2 ring of thiazole and 1,3,4-thiadiazole, as well as pyrazole were assessed for their activity against Candida albicans. Activity of majority of tested thioamides was larger as compared with that of the reference drugs. The electron parameters of obtained N-heterocyclic thioamides were determined and dependencies on their biological activity against Candida albicans were studied. The best electron compliance of produced bindings with the activity against Candida albicans was observed for the derivatives containing 1,3,4-thiadiazole ring.
Thioamides; antifungal activity; Candida albicans; electron parameters
In an effort to search for more active antiinflammatory agent, a series of pyrazolinylbenzidines and isoxazolylbenzidines was designed, synthesized, and screened for their potential as novel orally inflammation inhibitors. Compounds 4,4’-bis-(1”-acetyl-5”-substitutedaryl-2”-pyrazolin-3”-yl)benzidines (8-13) and 4,4’-bis-(2”-substitutedaryl-isoxazolin-4’-yl)benzidines (14-19) have been synthesized from 4,4’-bis-(substituted benzylidenyl-acetyl)benzidines (2-7). The structures of the products have been delineated by spectral and elemental analysis. Compounds 2-19 evaluated for antiinflammatory activity and acute toxicity and results are reported. The compound 4,4’-bis-[1”-acetyl-5”-(p-methoxyphenyl)-2”-pyrazolin-3’-yl)benzidine (9) showed more potent and dose-dependent antiinflammatory activity in comparison to reference drug.
Pyrazolinylbenzidines; isoxazolinylbenzidines; antiinflammatory activity; ulcerogenic liability; toxicity
Drug therapy accounts for a major portion of health expenditure. A useful strategy for achieving cost efficient healthcare is drug utilisation research as it forms the basis for making amendments in drug policies and helps in rational drug use. The present observational study was conducted to generate data on drug utilization in inpatients of our tertiary care hospital to identify potential targets for improving drug prescribing patterns. Data was collected retrospectively from randomly selected 231 medical records of patients admitted in various wards of the hospital. WHO Anatomical Therapeutic Chemical/Defined Daily Dose methodology was used to assess drug utilisation data and drug prescriptions were analysed by WHO core drug indicators. Antibiotics were prescribed most frequently and also accounted for majority of drug costs. The prescribed daily dose for most of the antibiotics corresponded to defined daily dose reflecting adherence to international recommendations. Brand name prescribing and polypharmacy was very common.78% of the total drugs prescribed were from the National List of Essential Medicines 2003. Restricting the use of newer and costlier antibiotics, branded drugs and number of drugs per prescription could be considered as targets to cut down the cost of drug therapysignificantly.
Drug utilisation; Defined daily dose; Prescribed daily dose; Polypharmacy; Essential medicines
Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na+/K+ ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na+/K+ ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.
Gymnema sylvestre; leptin; insulin; blood pressure; caspase-3; dyslipidemia
The petroleum ether leaf extract of Ficus krishnae has been evaluated for the management of diabetes in alloxan induced diabetic rats. Phytochemical screening of the leaf extract for various chemical compounds has also been carried out. Leaf extract was administered continuously for 21 days orally at a dose of 200 mg/kg. Along with this, the blood glucose level was monitored at regular intervals to understand the activity of the extract. The leaf extract has decreased the blood glucose level of diabetic rats which was comparable to an antidiabetic standard drug, glibenclamide, given at a dose of 2.5 mg/kg. It has been observed that the leaves of Ficus krishnae possess antidiabetic activity and it reduces the blood glucose level significantly. The phytochemical screening of leaf has revealed the presence of carbohydrates, flavonoids, tannins, glycosides, terpenoids, steroids, alkaloids, gums and mucilage, phlobatannins, reducing sugars and phenolic compounds. The Fourier Transform Infrared analysis of glibenclamide and leaf powder has displayed some common absorption spectra. This shows that leaf powder has a molecule which is close to glibenclamide. Wavelength Dispersive X-Ray Fluorescence spectroscopy have shown the presence of cellulose, Ca, Si, K, Cl, Mg, P, S, Al, Fe, Na, Sr, Pd, Zn, Mn, Cr, Mo, Br, Ni, Rb and Zr. It is assumed that these elements alongwith other chemical compounds of the plant species may play a role in the management of diabetes. The Raman Specta of both glibenclamide and leaf powder has also shown some similarities. The results obtained during the present investigation have revealed the antidiabetic activity of Ficus krishnae leaves. The phytochemical screening has indicated the various chemical constituents likely to be responsible for this activity. The Fourier Transform Infrared, Wavelength Dispersive X-Ray Fluorescence and Raman Specta of the leaf powder suggested that there is some glibenclamide like molecule or its derivatives which is imparting antidiabetic activity.
Diabetes; Ficus krishnae; glibenclamide; phytochemicals; FTIR; WD-XRF; Raman spectroscopy
Thiophene substituted chalcones (1a-e) were cyclised with thiourea in presence of potassium hydroxide to get 4-substituted-6-(thiophen-2-yl)pyrimidine-2-thiols (2a-e) which were then stirred with methyl iodide to obtain 4-substituted-2-(methylsulfanyl)-6-(thiophen-2-yl)pyrimidines (3a-e). Compounds (3a-e) were refluxed with different N-methylpiperazine and N-phenylpiperazine to afford 4-substituted-2-(4-methylpiperazin-1-yl)-6-(thiophen-2-yl)pyrimidines (4a-e) and 4-substituted-2-(4-phenylpiperazin-1-yl)-6-(thiophen-2-yl)pyrimidines (5a-e). The structures of all the newly synthesised compounds 4b, 4d, 5a and 5b showed good antibacterial activity at 40μg/mlconcentration. Compounds 4a, 4d, 4e, 5c and 5e showed significant antifungal activity at 40 μg/ml concentration compared with standard drugs.
2-Acetylthiophene; thiourea; piperazine; pyrimidine; antibacterial; antifungal
A series of 1,4-dihydropyrimidine derivatives 3(a-t) were prepared from Biginelli reactions by using ethyl acetoacetate, substituted benzaldehyde and thiourea in the presence of piperidine and ethanol. The compounds 3(a-t) were reacted with dimethylsulphate, diethylsulphate, butyl bromide and benzyl chloride to give the new series of compounds 4(a-t). The structures of the newly synthesized compounds 4(a-t) were established by IR, 1H NMR, Mass spectra and elemental analysis. The synthesized compounds were evaluated for their in vitro anticancer activity by using Sulforhodamine B assay method against the growth of four humans cancer cell lines, antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and for antifungal activity against Candida albicans and Aspergillus niger. The compounds exhibited good anticancer activity and moderate antibacterial and antifungal activities. Compounds 4b, 4c, 4d, 4g, 4i, 4n, 4o, 4q and 4s showed significant anticancer activity when compared with the doxorubicin as a standard reference drug.
Anticancer; antimicrobial; Biginelli reaction; cell line; dihydropyrimidine; SRB assay method
Renal ischemia reperfusion injury contributes patho-physiological imbalance of acute renal failure that comprises of generation of reactive oxygen species, nitric oxide and peroxynitrite and inflammation involving cytokine/adhesion molecule cascade, finally leads to cell death. Oxygen deprival associated with ischemia that in turn lead to decline ATP production is the characteristic feature usually addressed in the development of in vitro cell based ischemic model. In order to create oxygen deficit in the cell lines different approaches like chemical induction, enzymatic induction and anaerobic chamber models are widely used. However efficiencies of these models were varied and the present study was aimed to compare the suitability of these models in creating in vitro ischemia reperfusion in cell culture. In the chemical induced method we used different concentrations of rotenone, antimycin and sodium azide to inhibit electron transport chain and thereby reduced the ATP production, measured indirectly by cell viability assay. Among the chemical induced model, antimycin mediated cell injury was more reliable for ischemia reperfusion study. In the enzymatic model, comprises of glucose oxidase (3mM/s) and catalase (998 s-1 at 10:1 ratio) was used and found to be best among the three approaches as it can create injury in short experimental time and are reproducible. However anaerobic chamber method was not suitable for ischemia reperfusion study as it need more time to induce significant cell injury.
Renal ischemia reperfusion; LLC PK1; Rotenone; antimycin; enzymatic hypoxia; hydrogen sulfide