Isolation and characterization of a novel flavanone glycoside from an endemic plant Haplanthodes neilgherryensis.

The chemical characterization study of an endemic plant, Haplanthodes neilgherryensisis (Wight) R.B. Majumdar from Western Ghats of India, resulted in to the isolation of a new flavanone glycoside, 5-hydroxy-7-methoxy-8-O-ß-D-glucopyranosyl-2S-flavanone (1), along with 3 known flavonoids, 7-O-methyl dihydrowogonin (2), 7-O-methyl wogonin (3), andrographidine C (4). The structure of 1 was elucidated by using 1 D and 2 D NMR and HRMS experimental data, while for the known compounds, 1H NMR and mass spectrometry data were compared with the reported literature. Compound 1 was tested in vitro to check the improvement in uptake of glucose by the L6 rat skeletal muscle tissues and the observed EC50 value was 5.8 µM, while rosiglitazone showed EC50 of 2.7 µM.

Synthesis, antibacterial, anti-oxidant and molecular docking studies of imidazoquinolines.

Quinoline and imidazole derivatives have been playing a significant role in functional bioactivities and were potentially used as antibacterial, antifungal, anticancer, and anti-inflammatory drugs. Owing to the limitation of drug resistance, herein we synthesized thio-, chloro-, and hydroxyl-functionalized various imidazoquinolines by molecular hybridization approach. All the imidazoquinoline derivatives were examined for their antibacterial activity against selected bacterial pathogens by the agar well diffusion method. In addition, the anti-oxidant efficacy of imidazoquinolines was also tested using ferric reducing antioxidant power (FRAP). Among them, electron-withdrawing (-Cl) substituent containing imidazoquinoline 5f showed higher antibacterial and anti-oxidant activities than other imidazoquinolines and reached the effectiveness of the standard. In addition, compounds 4f, 5e, and 3f showed moderate antibacterial activity and other derivatives displayed weak activity against various pathogens. Molecular docking studies were also performed on selected imidazoquinoline derivatives (3f, 4f, and 5f), which showed high docking score and strong binding energy values. These results revealed that thio-imidazoquinoline could assist as a prototype for the designing of multidrug-resistant antibiotics against various microbial organisms.

Adult- Onset Centronuclear Myopathy.

Centronuclear myopathy (CNM) is a rare congenital myopathy that is characterized by centrally placed nuclei in the muscle fibers. Three forms of the disease are clinically recognized. The severe neonatal form, the childhood onset form, and an adult-onset form. We report a 50 year old male patient with centronuclear myopathy (CNM) in whom the disease manifested itself in the fifth decade of life without any family history of such illness.

Molecular Insights into the Genetic Diversity of Garcinia cambogia Germplasm Accessions

ABSTRACTIn this work, the genetic relationship among twelveGarcinia cambogia (Gaertn.) Desr. accessions were evaluated using Random Amplified Polymorphic DNA markers. The samples were part of the germplasm collected and maintained at NBPGR Regional station, Thrissur, India. Out of thirty RAPD primers used for screening, seven primers produced a total of 128 polymorphic markers in twelve accessions. The Polymorphic Information Content (PIC) ranged from 0.28 (OPA18) to 0.37 (OPA9) and Marker Index (MI) ranged between 3.61 (OPA12) and 5.93 (OPA3) among the primers used. Jaccard's coefficient of genetic similarity ranged between 0.07 and 0.64. The dendrogram constructed based on the similarity matrix generated from the molecular and morphological data showed the genetic relationship among the sampled accessions. Mantel matrix test showed a positive correlation (r = 0.49) between the cluster analysis of RAPD data and morphological data. The clustering pattern in the molecular dendrogram and Principle Coordinate Analysis (PCoA) showed that the genotypes were diverse, which was in congruence with the similarity index values and morphological dendrogram. High frequency of similarity values in the range of 0.11 to 0.17 suggested the existence of high genetic diversity among the accessions. The high level of genetic diversity among the studied accessions ofG.cambogia was also supported by the large variation in the morphological characters observed in the flowers, leaves, fruits and seeds of these sampled accessions. This is the first report for the molecular based genetic diversity studies for these accessions.

Comparative evaluation of anthelmintic and antibacterial activities in leaves and fruits of Garcinia cambogia (Gaertn.) desr. and Garcinia indica (Dupetit-Thouars) choisy

This study aimed to evaluate the in vitro anthelmintic activity and antibacterial activity of the extracts from the leaves and fruits of Garcinia indica (Dupetit-Thouars) Choisy and Garcinia cambogia (Gaertn.) Desr. using the Indian earthworm Pheretima posthuma. Two concentrations (25 and 50 mg/mL) of various extracts such as petroleum ether, chloroform, ethyl acetate, methanol and water were tested. Albendazole at the concentrations of 25 and 50 mg/mL was used as the standard reference. Significant anthelmintic effects of the fruits and leaves of G. cambogia and G. indica (P<0.05) were observed and the results were expressed in terms of paralysis and death time. All the extracts showed the dose dependent paralysis and death of earthworms. Among all the extracts used, methanol extract exhibited the highest activity. G. cambogia leaf extract (50 mg/mL) had 30% faster paralysis effect on earthworms than the standard reference. Furthermore, the antimicrobial activity of the methanol extracts of the fruits and leaves showed significant (P<0.05) activity against Gram-positive and Gram-negative bacteria. At a concentration of 500 µg/mL, G. indica fruit extract presented higher zones of inhibition against Pseudomonas aeruginosa and Staphylococcus aureus. Hence, it could be concluded that the leaves and fruits of G. indica and G. cambogia contained active anthelmintic and antibacterial phytochemicals, which could find their applications in pharmaceuticals.

Ag nanoparticles-anchored reduced graphene oxide catalyst for oxygen electrode reaction in aqueous electrolytes and also a non-aqueous electrolyte for Li-O2 cells.

Silver nanoparticles-anchored reduced graphene oxide (Ag-RGO) is prepared by simultaneous reduction of graphene oxide and Ag(+) ions in an aqueous medium by ethylene glycol as the reducing agent. Ag particles of average size of 4.7 nm were uniformly distributed on the RGO sheets. Oxygen reduction reaction (ORR) is studied on Ag-RGO catalyst in both aqueous and non-aqueous electrolytes by using cyclic voltammetry and rotating disk electrode techniques. As the interest in non-aqueous electrolyte is to study the catalytic performance of Ag-RGO for rechargeable Li-O2 cells, these cells are assembled and characterized. Li-O2 cells with Ag-RGO as the oxygen electrode catalyst are subjected to charge-discharge cycling at several current densities. A discharge capacity of 11 950 mA h g(-1) (11.29 mA h cm(-2)) is obtained initially at low current density. Although there is a decrease in the capacity on repeated discharge-charge cycling initially, a stable capacity is observed for about 30 cycles. The results indicate that Ag-RGO is a suitable catalyst for rechargeable Li-O2 cells.

A three-dimensional chemical phase pharmacophore mapping, QSAR modelling and electronic feature analysis of benzofuran salicylic acid derivatives as LYP inhibitors.

Lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, has a critical negative regulatory role in T-cell antigen receptor (TCR) and emerged as a promising drug target for human autoimmune diseases. A five-point pharmacophore with two hydrogen bond acceptors, one hydrogen bond donor and two aromatic ring features was generated for a series of benzofuran salicylic acid derivatives as LYP inhibitors in order to elucidate their anti-autoimmune activity. The generated pharmacophore yielded a significant 3D-QSAR model with r(2) of 0.9146 for a training set of 27 compounds. The model also showed excellent predictive power with Q(2) of 0.7068 for a test set of eight compounds. The investigation of the 3D-QSAR model has revealed the structural insights which could lead to more potent analogues. The most active and inactive compounds were further subjected to electronic structure analysis using density functional theory (DFT) at B3LYP/3-21(∗)G level to support the 3D-QSAR predictions. The results obtained from this study are expected to be useful in the proficient design and development of benzofuran salicylic acid derivatives as inhibitors of LYP.

Identification of potential HIV-1 integrase strand transfer inhibitors: in silico virtual screening and QM/MM docking studies.

HIV-1 integrase (IN) is a retroviral enzyme that catalyses integration of the reverse-transcribed viral DNA into the host genome, which is necessary for efficient viral replication. In this study, we have performed an in silico virtual screening for the identification of potential HIV-1 IN strand transfer (ST) inhibitors. Pharmacophore modelling and atom-based 3D-QSAR studies were carried out for a series of compounds belonging to 3-Hydroxypyrimidine-2,4-diones. Based on the ligand-based pharmacophore model, we obtained a five-point pharmacophore with two hydrogen bond acceptors (A), one hydrogen bond donor (D), one hydrophobic group (H) and one aromatic ring (R) as pharmacophoric features. The pharmacophore hypothesis AADHR was used as a 3D query in a sequential virtual screening study to filter small molecule databases Maybridge, ChemBridge and Asinex. Hits matching with pharmacophore hypothesis AADHR were retrieved and passed progressively through Lipinski's rule of five filtering, molecular docking and hierarchical clustering. The five compounds with best hits with novel and diverse chemotypes were subjected to QM/MM docking, which showed improved docking accuracy. We further performed molecular dynamics simulation and found three compounds that form stable interactions with key residues. These compounds could be used as a leads for further drug development and rational design of HIV-1 IN inhibitors.

Targeting Multidrug Resistant Mycobacterium tuberculosis HtrA2 with Identical Chemical Entities of Fluoroquinolones.

Tuberculosis is a highly communicable and chronic respiratory disease caused by pathogenic bacterium Mycobacterium tuberculosis. The drug - resistant species of Mycobacterium tuberculosis are tough to cure due to its resistant activity toward potential drugs. Available inhibitors of tuberculosis include few antimicrobial fluoroquinolone agents like ciprofloxacin, ofloxacin, and moxifloxacin to treat resistant Mycobacterium strains. Literature study elucidates that macromolecular target namely, HtrA2 of Mycobacterium tuberculosis play a dual role of protease and chaperone. These two activities are dependent on temperature, with low temperatures promoting the chaperone function and high temperatures promoting serine protease activity. Under normal physiological conditions HtrA2 acts as a quality control factor and promotes cell survival. In the present investigation, we screened fluoroquinolone such as ciprofloxacin, moxifloxacin and ofloxacin and their analogues based on better Docking score, absorption, distribution, metabolism and excretion screening and Lipinski's rule of 5, to find out their efficiency on resistant strain through in silico study. From the results observed, the analogues are suggested to be potent inhibitors of HtrA2 with sufficient scope for further exploration.