IR@IIIM - Indian Institute of Integrative Medicine (CSIR)
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Design, Synthesis, and Biological Testing of 4β-[(4-Substituted)-1,2,3-triazol-1-yl]podophyllotoxin Analogues as Antitumor Agents
No full textA series of 4b-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin analogues have been synthesized
with high regio-selectivity by employing copper(I)-catalyzed 1,3-dipolar cycloaddition of 1-O-propargyl monosaccharides with C4b-azido podophyllotoxin and C4b-azido-49-O-demethyl podophyllotoxin.All the compounds were evaluated for their anticancer activity against a panel of six human cancer cell lines. Among these, 49-O-demethyl podophyllotoxin congeners are showing promising anticancer activity mainly against HCT-15 (colon) and DU-145 (prostate) cells
Citral derived amides as potent bacterial NorA efflux pump inhibitors
No full textMonoterpene citral and citronellal have been used as starting material for the preparation of 5,9- dimethyl-deca-2,4,8-trienoic acid amides and 9-formyl-5-methyl-deca-2,4,8-trienoic acid amides. The amides on bioevaluation as efflux pump inhibitors (EPIs) against Staphylococcus aureus 1199 and NorA overexpressing S. aureus 1199B bacteria resulted in the identification of several of these as potent EPIs. Many of these amides have been shown to possess potency higher or equivalent to known EPIs such as reserpine, verapamil, carsonic acid, and piperine. In this communication, we report a convenient synthesis of alkenyl amides, their bioevaluation and identification as efflux pump inhibitors against S. aureus
Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus
No full textObjectives: Evaluation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus.
Methods: A library of piperine-derived compounds was evaluated for their potential to inhibit ethidium
bromide efflux in NorA-overexpressing S. aureus SA 1199B. The active compounds were then individually combined with ciprofloxacin to study the potentiation of ciprofloxacin’s activity.
Results: Based on the efflux inhibition assay, a library of 200 compounds was screened. Three piperine analogues, namely SK-20, SK-56 and SK-29, were found to be the most potent inhibitors of the NorA efflux pump. These inhibitors acted in a synergistic manner with ciprofloxacin, by substantially increasing its activity against both NorA-overexpressing and wild-type S. aureus isolates. These analogues were 2- to 4-fold more potent than piperine at a significantly lower minimal effective concentration.
Furthermore, these inhibitors also significantly suppressed the in vitro emergence of ciprofloxacin-resistant S. aureus.
Conclusions: A newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting
Simultaneous high-performance liquid chromatographic determination of Cedrus deodara active constituents and their pharmacokinetic profile in mice
No full textA specific and sensitive high-performance liquid chromatographic (HPLC) method with photodiode-array (PDA) ultraviolet detection was developed for the simultaneous determination of three bioactive constituents of Cedrus deodara namely wikstromol, matairesinol and dibenzylbutyrolactol in mouse plasma. In solid-phase extraction (SPE) these constituents were successfully separated using a C18 column by isocratic elution
using acetonitrile:water containing hexanesulphonic acid, 32:68 (v/v). The flow rate was set at 1 ml/min and detector wavelength at 225 nm. Good linearity (r2 > 0.999) was observed over the studied range of 0.015–5.0 �g/ml for wikstromol and 0.030–5.0 �g/ml for matairesinol and dibenzylbutyrolactol.The CV values of intra-day precision for wikstromol, matairesinol and dibenzylbutyrolactol were in between 1.8–6.9, 1.7–4.9 and 1.6–4.2% and values of inter-day precision were in between 10.4–12.2, 9.7–11 and 10–11.2%, respectively. The extraction recoveries at low to high concentration were greater than 98, 83 and 87% for each analyte, respectively. The LOQ for wikstromol was 0.015 �g/ml and for both matairesinol and dibenzylbutyrolactol it was 0.030 �g/ml. The developed method was used to determine the pharmacokinetics of the three analytes in mice after intraperitoneal administration of CD-3
Immobilization of Lipase by Entrapment in Ca-alginate Beads
No full textThe lipase-producing strain, Arthrobacter sp. (ABL), isolated was immobilized in Ca-alginate beads by entrapment. The alginate beads were prepared as an aqueous mixture of sodium alginate, the cells and CaCl2 to
increase its reusability, and overall enzyme stability. Various parameters like alginate and CaCl2 concentration, lipase units loading and bead size were
evaluated for optimum immobilization yield. It was observed that with the increase in alginate concentration, the yield of immobilized enzyme also increased up to a limit. A similar pattern was observed with CaCl2 addition;
the optimum concentrations of alginate and CaCl2 observed were 1.5% (w/v) and 2%, respectively. The concentration of enzyme entrapped in the beads with
an activity of 5 units per gram of wet beads was obtained by the addition of 100 units in 10mL of slurry; beyond this amount a very little increase in activity was observed. The maximum immobilization yield was observed with a 1.2mm
bead size; increased bead sizes decreased the yield of immobilization. After optimization of all the parameters, a 40% yield of lipase (ABL) activity was observed in the Ca-alginate beads. These lipase beads were used for 10 cycles for the hydrolysis of triglycerides without any loss in activity. The entrapped lipase was more stable over a wide range of temperatures, pH, and storage time as
compared to free enzyme
Indium trichloride promoted stereoselective synthesis of O-glycosides from trialkyl orthoformates
No full textA novel, highly stereoselective method for O-glycosylation of glycals and glycosylbromides is developed using orthoformates as acceptors in the presence of InCl3 to afford the corresponding O-glycopyranosides in 66–94% yield. Both perbenzyl and peracetyl glycals afford the corresponding 2,3-unsaturated-O-glycosides with high a-selectivity. Stoichiometric amounts of orthoformates are sufficient to bring about this transformation instead of large excesses of alcohols
Phylogenetic Analyses of Archaeal Ribosomal DNA Sequences from Salt Pan Sediment of Mumbai, India
No full textThe archaeal diversity in salt pan sediment from Mumbai, India, was investigated by 16S rDNAdependent molecular phylogeny. Small-subunit rRNA (16S rDNA) from salt pan sediment metagenome were amplified by polymerase chain reaction (PCR) using primers specific to the domain archaea. Thirty-two unique phylotypes were obtained by PCR-based RFLP of 16S rRNA genes using endonucleases Hae111 and Msp1, which were most suitable to score the genetic diversity. These phylotypes spanned a wide range within the domain Archaea including both Crenarchaeota and Euryarcheaota. However, none of the retrieved Crenarchaeota sequences could be grouped with previously cultured Crenarchaeota. Of all the Euryarcheaota sequences, three sequences were related to Haloarchaea, two were related to cultured Methanosarcina sp., and the remaining sequences were affiliated with uncultured Methanosarcina sp., Methanogenium sp., and Methanolobus sp. Most of the sequences determined were closely related to the sequences that had been previously obtained from metagenome of a variety of marine environments. The phylogenetic study of a site investigated for the first time revealed the presence of a highly diverse archaeal population and may represent novel sequences and organisms specially adapted to the salt pan sediment of Mumbai. These findings are of fundamental value for understanding the complexity of salt pan ecosystems
Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors
No full textBased on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor(EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis,bioevaluation and structure related activity of these efflux pump inhibitors
Immune up regulatory response of a non-caloric natural sweetener, stevioside
No full textImmunomodulation is a process, which alters the immune system of an organism by interfering with its functions. This interference results in either immunostimulation or immunosuppression. An immunomodulator is any substance that helps to regulate the immune system. This “regulation” is a normalization process, so that an immunomodulator helps to optimise immune response.Immunomodulators are becoming very popular in theworldwide natural health industry as these do not tend to boost immunity, but to normalize it. Keeping this in view, major efforts have to be directed to modulate the immune responses, to permit effective treatment
of various ailments associated with immune system and thus the development of a safe and effective immunomodulator for clinical us.Leaves of Stevia rebaudiana are a source of several sweet glycosides of steviol. The major glycoside, stevioside, diterpenoid glycoside—is used in oriental countries as a food sweetener. Its medical use is also reported as a heart tonic. Besides, it is used against obesity, hypertension, and stomach burn and to lower uric acid levels. Here in this study, stevioside was tested for its immunomodulatory activity on different parameters of the immune system at three different doses (6.25, 12.5 and 25 mg/kg p.o.)on normal as well as cyclophosphamide treated mice. Stevioside was found effective in increasing phagocytic activity, haemagglutination antibody titre and delayed type hypersensitivity. In parallel, stevioside substantially increase proliferation in the LPS and
Con A stimulated B and T cells, respectively. Present study, therefore, reveals that the drug holds promise as immunomodulating agent, which acts by stimulating both humoral as well as cellular immunity and phagocytic function
Synthesis and cytotoxic activity of some novel polycyclic γ-butyrolactones
No full textBaeyer–Villiger oxidation of 5-aryl-7,11,11-trimethyltricyclo[5.4.0.03,6]-undec-1-en-4-ones 4a–h by
H2O2 and formic acid in methanol yields mixtures of 3b,7,7-trimethyl-3-phenyl-3,3a,3b,4,5,6,7,8a-octahydro-
1H-indeno-[1,2-c]furan-1-ones 8a–h and 3b,7,7-trimethyl-3-phenyl-3,3a,3b,4,5,6,7,8a-octahydro-1H-indeno-[1,2-c]furan-2-ones 9a–h in high yields. The obtained butyrolactones 8a–h display cytotoxic activity against a number of human cancer cells