Cytotoxic potential of Cissus quandrangularis on Allium cepa root meristem

<p>Apoptosis is a developmental and regulated process which may occur as a result of the cytogenetic changes in the cell. <em>Cissus quandrangularis</em> is a xerophytic plant that belongs to the family Vitaceae, commonly distributed throughout the hotter parts of India and Sri Lanka. An attempt had been made to explore the apoptosis-mediated cytotoxic potential of <em>C.</em> <em>quadrangularis</em> on <em>Allium cepa</em>. Cytogenetic activities of the plant were revealed using DAPI staining and <em>in situ</em> visualization of cell death was carried out with the help of Evans blue staining. The presence of clastogenic (nuclear lesions, chromosome bridges, chromosome breakage and pulverization of chromosomes) and non-clastogenic abberations (ball metaphase, stellate metaphase, chromosome clumping and early movement of chromosomes) observed under fluorescent microscope shows the cytotoxic effect of the plant extract. The quantification of cell death was measured by reading absorbance at 600 nm using the spectrophotometer. The cytotoxic effects on <em>Allium</em> root tips shows the apoptotic potential of the plant extract and the present study enlightens the anticancer potential of the plant.</p><p> </p><p> </p><p> </p><p> </p><h2> </h2><h2> </h2><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p><p> </p>

Development and evaluation of floating tablet of metoprolol succinate for increased bioavailability

<p>The present study is based on development and evaluation of gastroretentive floating tablets of metoprolol succinate by direct compression method, to increase the oral bioavailability of MS. For this, we used a combination of two different hydrophilic polymers that is polyethylene oxide PEO N-80 (X1) and hydroxy ethylcellulose HEC (X2) as independent variables and studied its effect on drug release (as dependent variable) at 20h for MS. A 3² factorial design was used for optimization purpose.</p><p>The DSC result shows no interaction between two polymers and the drug (MS). Further, in vitro drug release studies have shown a sustained drug release for more than 20h in upper gastrointestinal region (stomach). In vivo study using rabbits have shown increased AUC_0-24(bioavailability) of prepared optimized F6 formulation as compared to the marketed sustain release tablet of MS. Stability study shows no comparable differences on physical parameters and the drug release after 3 months of accelerated stability testing. Hence, we can conclude that a floating tablet containing combination of hydrophilic polymers can be used for gastric retention for more than 20hr which will increase the oral bioavailability of MS.</p>

Protein extracts from streptomyces sps. inhibits beta-lactamases secreted by pathogenic bacteria

<p>Beta-lactamases are enzymes produced by pathogenic microorganisms which exhibit resistance to beta-lactam group of antibiotics and are of considerable clinical importance. In our study, we examined the pathogenic organisms for the secretion of beta-lactamase using the antibiotic ampicillin. The extracted beta-lactamase from the isolates was characterized biochemically for enzyme activity and to initiate their inhibition activities. The protein extracts separated from the potential actinomycetes species were analyzed by targeting against the beta lactamase enzyme activity. The beta-lactamase enzymes from bacterial isolates were purified from the cell free culture extract and activity was estimated spectrophotometrically.<em> </em>The actinomycetes isolated from the soil source were tested for their efficiency to inhibit the beta-lactamase enzyme activity. The protein fractions were extracted by salt precipitation using ammonium sulfate and further salt removal by dialysis technique. The assays for enzyme inhibition were performed by plate well diffusion along with absorbance readings of the enzyme and substrate using spectrophotometer. The beta-lactamase enzyme activity of <em>Proteus</em> sp. had shown highest enzymatic activity followed by <em>Staphylococcus aureus </em>and <em>Pseudomonas </em>sp<em>. </em>The protein extracts of four actinomycetes isolates that showed beta-lactamase inhibition were identified belonging to the genus <em>Streptomyces </em>based on their colony morphology, microscopic observation, and biochemical tests. The beta-lactamase inhibition activities were analyzed to combat antibiotitc resistances exerted by the pathogenic bacteria in infections.</p><p> </p>

Recent advancesin the development of novel drug delivery systems for the prophylaxis of malaria

<p>The present review high-lights the advancement in nanoparticles formulations for the prophylaxis of malaria. An attempt has been made to describe various novel drug delivery systems based on approaches such as polymeric, metallic, natural, chitosan/antisense (AS) and chitosan/sense (S) oligodeoxynucleotide based nanoparticles etc. for the treatment of malaria. The polymer such as chitosan, hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone; the metal like gold and silver and other carriers such as glyceryl-dilaurate, albumin etc. have been explored for the development of novel nanoparticles formulations. These developed nanoparticles formulation have improved the targeted drug delivey of various clinically used antimalarial therapeutic agents such as hydroxychloroquine, curcumin, artemisinin, artemether and lumefantrine etc.</p>

Investigating the phase-solubility and compatibility study of anticancer drug complexed with β-cyclodextrin and HP–β-cyclodextrin

Poor aqueous solubility and dissolution rates are critical problems that hinders the formulation, development and delivery of most of BCS class II and class IV drugs. Gefitinib is a cytotoxic chemotherapeutic drug used in treatment of cancer. The objective of the present study was to investigate the drug-cyclodextrin compatibility study by FTIR and DSC study. The phase solubility study revealed formation of 1:1 stoichiometry binary inclusion complex. The complex was prepared by kneading method. FT-IR spectra provided the data indicating that the HP-β-CD was more effective than β-CD. Differential scanning calorimetry thermograms indicated stronger amorphization and entrapment of gefitinib with HP-β-CD.

Synthesis and antimicrobial activity of N-[4-(3-Oxo-3-phenyl-propenyl)-phenyl]-2-(4-phenyl-5-pyridine-4yl-4H-[1,2,4]triazole-3-ylsulfanyl)-acetamide

<p class="Default">A new series of<em> </em><em><span>N-</span></em><span>[4-(3-Oxo-3-phenyl-propenyl)-phenyl]-2-(4-phenyl-5-pyridine-4yl-<em>4H</em>-[1,2,4]triazole-3-ylsulfanyl)-acetamide</span> have been synthesized by the claisen-schimodt condensation of <em>N</em>-(4-Acetyl-phenyl)-2-(4-phenyl-5-pyridin-4-yl-4<em>H-</em>[1,2,4]triazole-3-ylsulfanyl) and various aldehyde. The novel compounds structure has been established on the basis of their substituted aldehyde derivatives. All the compounds were characterized by FT-IR, Mass, and ¹H-NMR spectroscopy. These new compounds were evaluated for their in vitro antibacterial activity and anti-fungal activity.</p>

Purified Quercetin From in vitro Cell Suspension Cultures of Caesalpinia pulcherrima Sw. and Its Antimicrobial Potentials

Tribal people use the flower extract of <em>Caesalpinia pulcherrima<strong> </strong></em>to cure liver, stomach and skin disorders in Indian traditional medicine. This study aimed to evaluate the protective roles of purified quercetin extracted from suspension culture of <em>C. pulcherrima</em> against selected bacterial and fungal pathogens. A simple protocol was developed for callus production using leaf explants<em>.</em> 2, 4-D (2.5 mg/l), BAP (2.5 mg/l) + kin (1 mg/ml) was effective for optimal callus induction. Subsequently, cell suspension culture was established. Role of effect of elicitors in cell suspension culture was carried. Sucrose, ABA and salicylic acid (SA) at different concentrations influenced cell biomass and quercetin accumulation. Cells cultured in the medium fortified with 45 g/L sucrose without ABA/SA showed the highest quercetin content (16.5 mg/g). Flavonoids was purified, fractionated by HPLC-DAD followed by NMR revealed the presence of quercetin, isoquercetin, quercetrin, rutin, quercetin 3-O-β-D-xyloside, quercetin 3-Oarabinopyranoside, quercetin 3-O- α-arabinopyranosyl (1→2) β-galactopyranoside, isorhamnetin 3-O-rutinoside and an unknown compound. Subsequently, anthocyanin was evaluated for antimicrobial activity against selected Gram-positive bacteria (<em>S. aureus, Bacillus subtilis</em>, and <em>Enterococcus faecalis</em><em>)</em>, Gram-negative bacteria (<em>E. coli, </em>and <em>Pseudomonas aeruginosa</em>) and fungi such as <em>Aspergillus flavus, Candida albicans </em>and <em>Trichophyton rubrum</em>. Quercetin was found to be active against four bacteria and the fungi- <em>Candida albicans</em>. The highest inhibitory effects were found on <em>S. aureus</em> and <em>Enterococcus faecalis</em>. Gram negative bacteria showed more resistance i.e., with insignificant MIC and MBC values. Among the fungi, <em>Aspergillus flavus</em> and <em>Trichophyton rubrum</em> displayed remarkable MIC and MKC values. These results suggest that quercetin may be used as a natural antimicrobial agent. Future works are designed to trace the molecular mechanism of antimicrobial potentiality of quercetin against these tested pathogens

Formulation and Evaluation of Sustained Release Tablets of Nateglinide by Using natural polymers

<p>The purpose of this research work was to formulate and evaluate the sustained release tablets of <em>Nateglinide</em> 500mg, an antidiabetic drug. <em>Nateglinide </em>is an oral hypoglycemic agent. The tablets are prepared by direct compression method. The formulations were optimized by incorporating varying composition of Xanthan gum and guar gum as polymers, lactose as flow aid and magnesium stearate as lubricant. All the excipients are tested for compatibility with drug, which revealed that there was no physical and chemical interaction occurred. The Preformulation parameters such as bulk density, tapped density, compressibility index and Hausner’s ratio were analyzed. The friability, drug content, loss on drying, bulk density and percentage yield was evaluated for tablets. The effect of these variables on drug release also studied. The In-Vitro drug release studied were Performed in the USP dissolution apparatus-II using pH 0.1N HCl as dissolution media at 75 rpm speed and temperature of 37^oc ± 5^oc. The sampling was done at periodic time intervals of 1,4,8,12,16,20 and 24 hours and was replaced by equal volume of dissolution media after each withdrawal. The cumulative amount of drug release at different intervals is estimated using UV method. Based on the evaluation result the formulations F-7 was selected as best formulation. The tablets were found to follow first order kinetics and Higguchi mechanism of drug release, ‘n’ value is less than 0.5 which confirms that the drug release through the matrix was fickian diffusion. </p>

Virtual Screening and ADMET Studies to Identify KSP Inhibitors as Anticancer Therapeutics

<p>Virtual Screening plays an important role to achieve binding affinity, receptor and library pre-processing, docking, scoring and top scoring hits. Optimization of drug ADME parameters continues to play an important role to ensure that the exposure is sufficient to achieve proof of concept, and ultimately efficacy, safely in clinical trials to address unmet medical need.<strong> </strong>In order to identify potential inhibitors we employed various computational approaches. In this work, we computationally screened and analyzed 60 analogs and further tested their ADME/T profiles.<strong> </strong>Library of the molecules was constructed based upon structural modifications of pyrimidines and indole nucleus. Structural modifications were performed for the series of 4-(3-hydroxyphenyl)-6-methyl-2-oxo-N-substituted[(Z)-(2-oxoindolin-3-ylidene)amino]-3,4-dihydro-1H-pyrimidine-5-carboxamide derivatives in an order to get better binding energies as compared with Ispinseb. The molecules with better (lower) binding energies were subjected to predict ADMET properties. Ten molecules from the series IP1-IP60 were found acceptable with binding energies and pharmacokinetic properties. On the basis of the binding energies and ADMET properties we have identified compound IP2 and IP4 to be the best interacting molecules. The molecules with acceptable ADMET properties and better binding energies were prioritized for synthesis and anticancer evaluation. </p>