A study on antimicrobial and anticancer properties of Cissus quadrangulris using lung cancer cell line.

Cissus quadrangularis plant from Vitaceae family, native in India. Many parts of this plant have medicinal values but most precious is stem of this plant. In past years number of studies reported their activities and secondary metabolites in Cissus quadrangularis plant and their pharmacological activities and uses in traditional medicine system. It is reported to possess excellent medicinal properties and potent fracture healing properties, antimicrobial, antiulcer, antioxidative, cholinergic activity and beneficial effect on cardiovascular diseases, possesses antiulcer and cytoprotective property in indomethacin-induced gastric mucosal injury. The aim of this study was to determine the qualitative phytochemical analysis, antimicrobial activity, cell viability and in vitro anticancer activity of a potential of Cissus quadrangularis stem extract against A549 human lung cancer cell line. The disc diffusion method was employed to determine the antimicrobial activity of Cissus quadrangularis stem extract and showed potential antibacterial and antifungal activity against various microorganisms. Results have shown that Stem methanolic extract induced a significant decrease of tumour cell viability. The cell viability assay clearly showed that the cells treated with Cissus quadrangularis methanolic extract has significantly reduced the lung cancer cell viability in a dose dependant manner. The stem methanolic extract was tested for the in vitro antiproliferative potential on A549 human lung cancer cell line using different concentrations, namely 1000, 62.5 and 7.8 µg/ml. We observed the IC50 dose at 65.2 µg/ml concentration. In cell culture A549 cells treated with Cissus quadrangularis stem methanolic extract in 24 h the cells growth is controlled.

Comparative analyses of PAP smear data in pre and postmenopause Indian women.

PAP smear is one of the best screening tools available for early detection of cervical cancer. Hence, we conducted a retrospective study at the Department of Pathology, Sree Balaji Medical College and Hospital over a period of one year by collecting PAP smear data. A total of 978 smears were collected out of which 59% were premenopausal and 41% were post menopausal women. Data shows that the prevalence of pre malignant and malignant lesions were more among the women of post menopausal age group than the pre menopausal age group.

Xanthine Oxidase Inhibitory Activity, Chemical Composition, Antioxidant Properties and GC-MS Analysis of Keladi Candik (Alocasia longiloba Miq).

Alocasia longiloba, locally known as 'Keladi Candik', has been used traditionally to treat wounds, furuncle and joint inflammations. A. longiloba can be a new source of herbal medicine against hyperuricemia by inhibiting the activity of xanthine oxidase enzyme, the enzyme which is responsible for the development of hyperuricemia in human. Existing xanthine oxidase inhibitors (XOI drugs) show several side effects on gout patients. Therefore, an alternative herbal medicine from plants, with high therapeutic property and free of side effects, are greatly needed. This study was conducted to evaluate XO inhibitory activity, chemical composition, antioxidant activity and GC-MS profile of A. longiloba. Our results showed that ethanolic petiole extract exhibited the highest XO inhibitory activity (70.40 ± 0.05%) with IC50 value of 42.71 µg/mL, followed by ethanolic fruit extracts (61.44 ± 1.24%) with the IC50 value of 51.32 µg/mL. In a parallel study, the phytochemical analysis showed the presence of alkaloid, flavonoid, terpenoids, glycoside and saponin in petiole and fruit extracts, as well as higher total phenolic and flavonoid contents and strong scavenging activity on DPPH and ABTS antioxidant assay. The GC-MS analysis of fruit and petiole extracts revealed the presence of various compounds belonging to different chemical nature, among them are limonen-6-ol, α-DGlucopyranoside, paromomycin, aziridine, phenol, Heptatriacotanol, Phen-1,2,3-dimethyl and Betulin found in ethanolic fruit extract, and Phen-1,4-diol,2,3-dimethyl-, 1-Ethynyl-3,trans(1,1-dimethylethyl), Phenol,2,6-dimethoxy-4-(2-propenyl)- and 7-Methyl-Z-tetradecen-1-olacetate found in ethanolic petiole extract. Some compounds were documented as potent anti-inflammatory and arthritis related diseases by other researchers. In this study, the efficiency of solvents to extract bioactives was found to be ethanol > water, methanol > hexane > chloroform. Together, our results suggest the prospective utilization of fruit and petiole of A. longiloba to inhibit the activity of XO enzyme.

Protective role of (Bronco-T) against formaldehyde induced antioxidant, oxidative and histopathological changes in lung of male Wistar rats.

The present study was sought to evaluate the oxidative, antioxidant status and histopathological changes by the acute chronic exposure of formaldehyde. Bronco-T a poly-herbal formulation treatment, changes the oxidative, antioxidant status and histopathology of rat lungs with antioxidant and regenerative property. In this experiment thirty adult male albino Wister rats were used for the study and subdivided in to five groups consist of 6 rats for each group. Group-I served as control and the other 4 groups such as II, III, IV and V are considered as experimental. The control and treatment rats are maintained for 21 days of experimental period. Experimental rats are exposed to 40 percent formaldehyde for 1 h treated with Bronco-T and salbutamol. In the present investigation, the formaldehyde exposed rats a series of free radical chain reactions were grimly provoked, the evaluation of antioxidant enzymes (SOD, CAT), other enzymes oxidative enzymes (G-6-PDH, SDH) and (ALT, ALAT and LDH) were measured. A clear assertive imbalance between oxidation and anti-oxidation status was critically observed, and oxidative stress was clearly exacerbated in lung tissue leading to altrations in architecture of lung histopathology. Oral gavage Bronco-T exhibits a beneficial action by bringing normal architecture in lung tissue of formaldehyde inhaled rats with antioxidant properties. Bronco-T treatment may be a suitable remedy for formalin occupational diseases.

CGMD: An integrated database of cancer genes and markers.

Integrating cancer genes and markers with experimental evidence might provide valuable information for the further investigation of crosstalk between tumor genes and markers in cancer biology. To achieve this objective, we developed a database known as the Cancer Gene Marker Database (CGMD), which integrates data on tumor genes and markers based on experimental evidence. The major goal of CGMD is to provide the following: 1) current systematic treatment approaches and recent advances in different cancer treatments; 2) the aggregation of different genes and markers by their molecular characteristics and pathway associations; and 3) free access to the data compiled by CGMD at http://cgmd.in/. The database consists of 309 genes and 206 markers, as well as a list of 40 different human cancers, with detailed descriptions of all characterized markers. CGMD provides complete cancer annotations and molecular descriptions of cancer genes and markers such as CpG islands, promoters, exons, PDB structures, active sites and domains.

Design, Synthesis, In Silico and In Vitro Studies of Substituted 1, 2, 3, 4- Tetrahydro Pyrimidine Phosphorus Derivatives.

Molecular docking studies of the designed two series (4a-l, 6a-l, 9 and 10) of novel substituted phosphorylated 1, 4-dihydropyridine and 1,2,3,4-tetrahydropyrimidine derivatives against the drug targets of DHFR from Bacillus cereus, LpxC from Pseudomonas aeruginosa, IDH from E. coli and MurB from Staphylococcus aureus were encouraged for their synthesis. These compounds were synthesized from substituted aromatic aldehydes, thiourea/urea and ethyl acetoacetate in the presence of polyphosphoric acid (PPA). These were further phosphorylated with diethyl (2-chloroethoxy) methyl phosphonate to get the desired products. In vitro anti-bacterial activity against the specified bacterial strains related to docked protein exhibited good inhibitory activity at different dose concentrations. Quantitative Structure Activity Relationship (QSAR) descriptors of the designed structures have demonstrated their satisfactory drug like properties. The results from Molecular Docking, QSAR descriptors and in vitro anti-bacterial activities led to the identification of safer and potential antibacterial agents of the title compounds screened. Compounds 4a, 4d, 4i, 6a, 6d, 9 and 10 were found to be potent antibacterial agents.

Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M.

The zoonotic disease brucellosis, a chronic condition in humans affecting renal and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of Gram-negative, facultative, intracellular pathogens. The mode of transmission and the virulence of the pathogens are still enigmatic. Transcription regulatory elements, such as rho proteins, play an important role in the termination of transcription and/or the selection of genes in Brucella. Adverse effects of the transcription inhibitors play a key role in the non-successive transcription challenges faced by the pathogens. In the investigation presented here, we computationally predicted the transcription termination factor rho (TtFRho) inhibitors against Brucella melitensis 16M via a structure-based method. In view the unknown nature of its crystal structure, we constructed a robust three-dimensional homology model of TtFRho's structure by comparative modeling with the crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as a template in MODELLER (v 9.10). The modeled structure was optimized by applying a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics program; v 2.9) and then evaluated by calculating the stereochemical quality of the protein. The flexible docking for the interaction phenomenon of the template consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not Commercial) database using a structure-based virtual screening strategy against minimized TtFRho. Docking simulations revealed two inhibitors compounds - ZINC24934545 and ZINC72319544 - that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex via a hydrogen bonding interaction by aromatic-π contacts, and the ADMET (absorption, distribution, metabolism, and excretion) analysis of best leads indicate nontoxic in nature with good potential for drug development.

Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M.

Brucella melitensis 16M is a Gram-negative coccobacillus that infects both animals and humans. It causes a disease known as brucellosis, which is characterized by acute febrile illness in humans and causes abortions in livestock. To prevent and control brucellosis, identification of putative drug targets is crucial. The present study aimed to identify drug targets in B. melitensis 16M by using a subtractive genomic approach. We used available database repositories (Database of Essential Genes, Kyoto Encyclopedia of Genes and Genomes Automatic Annotation Server, and Kyoto Encyclopedia of Genes and Genomes) to identify putative genes that are nonhomologous to humans and essential for pathogen B. melitensis 16M. The results revealed that among 3 Mb genome size of pathogen, 53 putative characterized and 13 uncharacterized hypothetical genes were identified; further, from Basic Local Alignment Search Tool protein analysis, one hypothetical protein showed a close resemblance (50%) to Silicibacter pomeroyi DUF1285 family protein (2RE3). A further homology model of the target was constructed using MODELLER 9.12 and optimized through variable target function method by molecular dynamics optimization with simulating annealing. The stereochemical quality of the restrained model was evaluated by PROCHECK, VERIFY-3D, ERRAT, and WHATIF servers. Furthermore, structure-based virtual screening was carried out against the predicted active site of the respective protein using the glycerol structural analogs from the PubChem database. We identified five best inhibitors with strong affinities, stable interactions, and also with reliable drug-like properties. Hence, these leads might be used as the most effective inhibitors of modeled protein. The outcome of the present work of virtual screening of putative gene targets might facilitate design of potential drugs for better treatment against brucellosis.

Molecular designing and in silico evaluation of darunavir derivatives as anticancer agents.

Darunavir is a synthetic nonpeptidic protease inhibitor which has been tested for anticancer properties. To deduce and enhance the anticancer activity of the Darunavir, we have modified its reactive moiety in an effective way. We designed 9 analogues in ChemBioOffice 2010 and minimized using the LigPrep tool of Schrödinger 2011. These analogues can obstruct the activity of other signalling pathways which are implicated in many tumors. Results of the QikProp showed that all the analogues lied in the specified range of all the pharmacokinetic (ADMET) properties required to become the successful drug. Docking study was performed to test its anticancer activity against the biomarkers of the five main types of cancers i.e. bone, brain, breast, colon and skin cancer. Grid was generated for each oncoproteins by specifying the active site amino acids. The binding model of best scoring analogue with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. An analysis of the receptor-ligand interaction studies revealed that these nine Darunavir analogues are active against all cancer biomarkers and have the features to prove themselves as anticancer drugs, further to be synthesized and tested against the cell lines.

Identification of Microbial Pathogens in Periodontal disease and Diabetic patients of South Indian Population.

Periodontitis have been referred to as the sixth complication of diabetes found in high prevalence among diabetic patients than among healthy controls. The aim of the present study was to examine the periodontal disease status among collected dental plaque samples. Chromosomal DNA was isolated and amplified by universal primers. The DNA was sequenced for bacterial confirmation and phylogenetic analysis performed for the evolutionary relationship with other known pathogens. No amplification products were observed in groups labeled non periodontal and non Diabetes (NP&ND) and non Periodontal and Diabetes (NP&D). But in the case of Periodontal and non Diabetes (P&ND) groups 22 amplified products were observed. In case of Periodontal and Diabetes (P&D), 32 amplified products were positive for microbes. Among the four microbial groups, Treponemadenticola, and Tannerella forsythia were found to be prevalent in P&D. The phylogenetic analysis of 16s rRNA of Treponemadenticola showed the relationship with other Treponema oral pathogen species and with the Spirochaetazuelaera. Tannerella forsythia shows its evolutionary relationship only with four oral pathogens (Macellibacteroidesfermentans, Porphyromadaceae bacterium, Parabacteroidesmeredae and Bacillus fosythus). Prevotellaintermedia also showed its evolutionary relationship only with Prevotella Spcs while Fusobacterium revealed close evolutionary relationship only with Porpiromonasgingivalis.

Isolation and characterization of ethanol tolerant yeast strains.

Yeast strains are commonly associated with sugar rich environments. Various fruit samples were selected as source for isolating yeast cells. The isolated cultures were identified at Genus level by colony morphology, biochemical characteristics and cell morphological characters. An attempt has been made to check the viability of yeast cells under different concentrations of ethanol. Ethanol tolerance of each strain was studied by allowing the yeast to grow in liquid YEPD (Yeast Extract Peptone Dextrose) medium having different concentrations of ethanol. A total of fifteen yeast strains isolated from different samples were used for the study. Seven strains of Saccharomyces cerevisiae obtained from different fruit sources were screened for ethanol tolerance. The results obtained in this study show a range of tolerance levels between 7%-12% in all the stains. Further, the cluster analysis based on 22 RAPD (Random Amplified polymorphic DNA) bands revealed polymorphisms in these seven Saccharomyces strains.

Comparison and correlation of binding mode of ATP in the kinase domains of Hexokinase family.

Hexokinases (HKs) are the enzymes that catalyses the ATP dependent phosphorylation of Hexose sugars to Hexose-6-Phosphate (Hex-6-P). There exist four different forms of HKs namely HK-I, HK-II, HK-III and HK-IV and all of them share a common ATP binding site core surrounded by more variable sequence that determine substrate affinities. Although they share a common binding site but they differ in their kinetic functions, hence the present study is aimed to analyze the binding mode of ATP. The analysis revealed that the four ATP binding domains are showing 13 identical, 7 similar and 6 dissimilar residues with similar structural conformation. Molecular docking of ATP into the kinase domains using Molecular Operating Environment (MOE) soft ware tool clearly showed the variation in the binding mode of ATP with variable docking scores. This probably explains the variable phosphorylation rates among hexokinases family.

Identification of substituted [3, 2-a] pyrimidines as selective antiviral agents: molecular modeling study.

A series of novel substituted dihydropyrimidine and 5H-thiazolo [3, 2-a] pyrimidine derivatives were designed and synthesized as a potential target to discover drugs fighting against the viral diseases. The main objective of the present work is to carry out the QSAR studies for all the series of the compounds starting from 4a to 6j to find out their molecular descriptors and predict the biological properties. All of them are showing the best QSAR descriptors, hence chosen for the prediction of anti-viral activity against Newcastle disease virus (NDV). Initially their inhibitory activity was predicted by molecular docking of these compounds against haemaglutinin-neuraminidase (HN) protein using molecular operating environment (MOE) software. Based on the best affinity and highest docking scores 4b, 5b and 6b were assayed in vivo on NDV infected chicks and it was found that there is significant improvement in the survival of the chicks with the treatment (P<0.05). 4b and 6b showed better curative effect than 5b at the dose concentration of 40 mg/kg body weight of chicks. The results from molecular docking study and biological assays can be inferred to consider these molecules as potential antiviral drugs.

Molecular modeling, docking and ADMET studies towards development of novel Disopyramide analogs for potential inhibition of human voltage gated sodium channel proteins.

The sodium "channelopathies" are the first among the ion channel diseases identified and have attracted widespread clinical and scientific interests. Human voltage gated sodium channels are sites of action of several antiarrhythmic drugs, local anesthetics and related antiepileptic drugs. The present study aims to optimize the activity of Disopyramide, by modification in its structures which may improve the drug action by reducing its side effects. Herein, we have selected Human voltage-gated sodium channel protein type 5 as a potent molecular target. Nearly eighty analogs of Disopyramide are designed and optimized. Thirty are selected for energy minimization using Discovery studio and the LigPrep 2.5. Prior to docking, the active sites of all the proteins are identified. The processing, optimization and minimization of all the proteins is done in Protein preparation wizard. The docking study is performed using the GLIDE. Finally top five ranked lead molecules with better dock scores are identified as having strong binding affinity to 2KAV protein than Disopyramide based on XP G scores. These five leads are further docked with other similar voltage gated sodium channel proteins (PDB IDs: 2KBI, 4DCK, 2L53 and 4DJC) and the best scoring analog with each protein is identified. Drug likeliness and comparative bioactivity analysis for all the analogs is done using QikProp 3.4. Results have shown that the top five lead molecules would have the potential to act as better drugs as compared to Disopyramide and would be of interest as promising starting point for designing compounds against various Sodium channelopathies.

Comparison and correlation of Simple Sequence Repeats distribution in genomes of Brucella species.

UNLABELLED: Computational genomics is one of the important tools to understand the distribution of closely related genomes including simple sequence repeats (SSRs) in an organism, which gives valuable information regarding genetic variations. The central objective of the present study was to screen the SSRs distributed in coding and non-coding regions among different human Brucella species which are involved in a range of pathological disorders. Computational analysis of the SSRs in the Brucella indicates few deviations from expected random models. Statistical analysis also reveals that tri-nucleotide SSRs are overrepresented and tetranucleotide SSRs underrepresented in Brucella genomes. From the data, it can be suggested that over expressed tri-nucleotide SSRs in genomic and coding regions might be responsible in the generation of functional variation of proteins expressed which in turn may lead to different pathogenicity, virulence determinants, stress response genes, transcription regulators and host adaptation proteins of Brucella genomes. ABBREVIATIONS: SSRs - Simple Sequence Repeats, ORFs - Open Reading Frames.