Synthesis of 1-(3',4',5'-trimethoxy) phenyl naphtho[2,1b]furan as a novel anticancer agent

3',4',5'-Trimethoxy benzoyl-naphthalene 2-O-acetic acid (5) underwent base catalysed intramolecular condensation to yield exclusively 1-(3',4',5'-trimethoxy) phenyl naphtho[2,1-b]furan 8. The cyclised product 8 has been characterised by spectroscopy. The product 8 showed significant anticancer activity against human cancer cell lines COLO320DM (colon), CaCO2 (colon) and WRL68 (liver) at 0.7, 0.65 and 0.50 microg/ml concentrations, respectively, in the in vitro MTT assay.     

Characteristic differences in metabolite profile in male and female plants of dioecious <Emphasis Type="Italic">Piper betle</Emphasis> L.

Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses. It belongs to the family Piperaceae and is a native of the tropics although it is also cultivated in subtropical areas. Flowering in P. betle occurs only in tropical regions. Due to lack of inductive floral cycles the plant remains in its vegetative state in the subtropics. Therefore, due to lack of flowering, gender distinction cannot be made the in the subtropics. Gender distinction in P. betle in vegetative state can be made using Direct Analysis in Real Time Mass Spectroscopy (DARTMS), a robust high-throughput method. DARTMS analysis of leaf samples of two male and six female plants showed characteristic differences in the spectra between male and female plants. Semi-quantitative differences in some of the identified peaks in male and female landraces showed gender-based differences in metabolites. Cluster analysis using the peaks at m/z 151, 193, 235 and 252 showed two distinct clusters of male and female landraces. It appears that male and female plants besides having flowers of different sexes also have characteristic differences in the metabolites representing two metabolic types.     

Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O(2)) than under 20% O(2) and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our (13)C NMR spectroscopic measurements indicate that (13)C-lactate is converted to (13)C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.     

Inhibition of lytic activity of Escherichia coli toxin hemolysin E against human red blood cells by a leucine zipper peptide and understanding the underlying mechanism

To investigate as to whether a peptide derived from hemolysin E (HlyE) can inhibit the cytotoxic activity of this protein or not, several peptides were examined for their efficacy to inhibit the lytic activity of the protein against human red blood cells (hRBCs). It was found that a wild-type peptide, H-205, derived from an amphipathic leucine zipper motif, located in the amino acid region 205-234, inhibited the lytic activity of hemolysin E against hRBCs. To understand the basis of this inhibition, several functional and structural studies were performed. Western blotting analysis indicated that the preincubation of HlyE with H-205 did not inhibit its binding to hRBC. The results indicated that H-205 but not its mutant inhibited the hemolysin E-induced depolarization of hRBCs. Flow cytometric studies with annexin V-FITC staining of hRBCs after incubation with either protein or protein/peptide complex suggested that H-205 prevented the hemolysin E-induced damage of the membrane organization of hRBCs. Tryptophan fluorescence and circular dichroism studies showed that H-205 induced a conformational change in HlyE, which was accompanied by the enhancement of an appreciable helical structure. Fluorescence studies with rhodamine-labeled peptides showed that H-205 reversibly self-assembled in aqueous environment, which raised a possibility that the H-205 peptide could interact with its counterpart in the protein and thus disturb the proper conformation of HlyE, resulting in the inhibition of its cytotoxic activity. The peptides derived from the homologous segments of other members of this toxin family may also act as inhibitors of the corresponding toxin.     

Gastroretentive drug delivery system of ranitidine hydrochloride: Formulation and in vitro evaluation

The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 3² full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous (X₁) and stearic acid (X₂) were selected as independent variables. The times required for 50% (t₅₀) and 80% drug dissolution (t₈₀), and the similarity factor f₂ were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity factor f₂ was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2=75) among all the batches, and this similarity is also reflected in t₅₀ (∼214 minutes) and t₈₀ (∼537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate retardant can produce a drug dissolution profile similar to a theoretical dissolution profile.     

A hierarchical method for finding optimal architecture and weights using evolutionary least square based learning

In this paper, we present a novel approach of implementing a combination methodology to find appropriate neural network architecture and weights using an evolutionary least square based algorithm (GALS).1 This paper focuses on aspects such as the heuristics of updating weights using an evolutionary least square based algorithm, finding the number of hidden neurons for a two layer feed forward neural network, the stopping criterion for the algorithm and finally some comparisons of the results with other existing methods for searching optimal or near optimal solution in the multidimensional complex search space comprising the architecture and the weight variables. We explain how the weight updating algorithm using evolutionary least square based approach can be combined with the growing architecture model to find the optimum number of hidden neurons. We also discuss the issues of finding a probabilistic solution space as a starting point for the least square method and address the problems involving fitness breaking. We apply the proposed approach to XOR problem, 10 bit odd parity problem and many real-world benchmark data sets such as handwriting data set from CEDAR, breast cancer and heart disease data sets from UCI ML repository. The comparative results based on classification accuracy and the time complexity are discussed.     

Co-operativity in non-covalent interactions in ternary complexes: a comprehensive electronic structure theory based investigation

The structure and stability of various ternary complexes in which an extended aromatic system such as coronene interacts with ions/atoms/molecules on opposite faces of the π-electron cloud were investigated using ab initio calculations. By characterizing the nature of the intermolecular interactions using an energy decomposition analysis, it was shown that there is an interplay between various types of interactions and that there are co-operativity effects, particularly when different types of interactions coexist in the same system.

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Graphical abstract Weak OH-π, π-π and van der Waals-π ternary systems are stabilized through dispersion interactions. Cation-π ternary systems are stabilized by through-space electrostatic interactions.

     

Viral diagnosis in Indian livestock using customized microarray chips

Viral diagnosis in Indian livestock using customized microarray chips is gaining momentum in recent years. Hence, it is possible to design customized microarray chip for viruses infecting livestock in India. Customized microarray chips identified Bovine herpes virus-1 (BHV-1), Canine Adeno Virus-1 (CAV-1), and Canine Parvo Virus-2 (CPV-2) in clinical samples. Microarray identified specific probes were further confirmed using RT-PCR in all clinical and known samples. Therefore, the application of microarray chips during viral disease outbreaks in Indian livestock is possible where conventional methods are unsuitable. It should be noted that customized application requires a detailed cost efficiency calculation.