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Amit K Keshari,1 Ashok K Singh,1 Vinit Raj,1 Amit Rai,1 Prakruti Trivedi,2 Balaram Ghosh,2 Umesh Kumar,3 Atul Rawat,3 Dinesh Kumar,3 Sudipta Saha1 1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, Uttar Pradesh, 2Department of Pharmacy, Birla Institute of Technology & Science Pilani, Hyderabad Campus, Hyderabad, Telangana State, 3Centre of Biomedical Research (CBMR), Sanjay Gandhi Post-Graduate Institute of Medical Sciences Campus, Raebareli Road, Lucknow, Uttar Pradesh, India Abstract: In our efforts to address the rising incidence of hepatocellular carcinoma (HCC), we have made a commitment to the synthesis of novel molecules to combat Hep-G2 cells. A facile and highly efficient one-pot, multicomponent reaction has been successfully devised utilizing a p-toluenesulfonic acid (p-TSA)-catalyzed domino Knoevenagel/Michael/intramolecular cyclization approach for the synthesis of novel 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogs bearing a bridgehead nitrogen atom. This domino protocol constructed one new ring by the concomitant formation of multiple bonds (C–C, C–N, and C=N) involving multiple steps without the use of any metal catalysts in one-pot, with all reactants efficiently exploited. All the newly synthesized compounds were authenticated by means of Fourier transform infrared spectroscopy, liquid chromatography–mass spectrometry, proton nuclear magnetic resonance spectroscopy, and carbon-13 nuclear magnetic resonance spectroscopy, together with elemental analysis, and their antitumor activity was evaluated in vitro on a Hep-G2 human cancer cell line by sulforhodamine B assay. Computational molecular modeling studies were carried out on cancer-related targets, including interleukin-2, interleukin-6, Caspase-3, and Caspase-8. Two compounds (4A and 6A) showed growth inhibitory activity comparable to the positive control Adriamycin, with growth inhibition of 50%

Baishakhi Ghosh,1,2 Nitin V Vanjare1 1Chest Research Foundation (CRF), Pune, Maharashtra, India; 2Faculty of Health and Biomedical Science (FOHBS), Symbiosis International University, Pune, Maharashtra, IndiaWe read the article by Porpodis et al1 with great interest. In this study, the authors have evaluated the effect of roflumilast on the phagocytic activity of systemic phagocytes in severe and very severe COPD patients by measuring the oxidative burst post-bacterial stimulation. The study group for this study involved 21 severe or very severe COPD patients who were administered roflumilast in addition to other COPD treatments such as long-acting beta-adrenoceptor agonists (LABA) + inhaled corticosteroids (ICS) + long-acting anti-muscarinic agent (LAMA) or ICS + LABA.View original paper by Porpodis and colleagues.

Aruna Bhattacharya,1 Rama Saha,1 Jayanta Biswas,2 Jhuma Biswas,1 Biswajit Ghosh11Institute of Postgraduate Medical Education and Research, 2NRS Medical College and Hospital, Kolkata, West Bengal, IndiaAbstract: A collision tumor is one where histology shows the presence of two distinct primaries involving the same organ without intermixture of individual cell types, ie, a side by side pattern. Here we present three rare cases of collision tumors involving the stomach and transverse colon. There were two cases of collision tumors involving the stomach, one of which was a combination of adenocarcinoma and low-grade non-Hodgkin's (mucosa-associated lymphoid tissue) lymphoma, and the other showed the presence of non-Hodgkin's lymphoma involving the entire stomach wall along with adenocarcinoma infiltrating the muscle layer. The third case comprised a mucinous adenocarcinoma and carcinoid tumor in the large gut.Keywords: collision tumor, histology, gastrointestinal tract

Magnetic nanometric skyrmions are small complex vortex-like topological defects, mainly found in non-centrosymmetric crystals such as MnSi. They have potential applications for future spintronic devices. In this article, the structural, electronic, and magnetic states of the Mn atoms in a polycrystalline MnSi thin film facing a c-sapphire substrate were studied using x-ray diffraction, x-ray photo-emission spectroscopy, resonance photoemission spectroscopy (RPES), and extended x-ray absorption fine structure (EXAFS). The valence band spectra indicate the metallic nature of the film. The RPES study reveals the presence of major itinerant Mn 3d states near EF and also the mixed Mn 3d and Si 3s–3p states from 5.3 to 11.3 eV. The EXAFS spectrum does not show the existence of oxygen vacancies in the system, and the obtained magnetic moment in the non-stoichiometric MnSi thin film is a combination of the partially itinerant and partially localized Mn 3d states. [ABSTRACT FROM AUTHOR]

With the escalating cost of health care, a cost-effective approach in the health delivery system has become essential. This management study in a large teaching hospital reveals a average loss of 43.3 days per bed in the matters of radiological investigations alone, an average waiting time of 10.4 days per operation, and an average length of stay of 14.3 days.

Double perovskite halides are a class of materials with diverse chemistries that are amenable to solution-based synthesis routes, and display a range of properties for a variety of potential applications. Starting from a consideration of the octahedral and tolerance factors of ∼2000 candidate double perovskite compounds, we compute structural, electronic, and transport properties of ∼1000 using first-principles calculations based on density-functional-theory methods. The computational results have been assembled in a database that is accessible through the Materials Project online. As one potential application, double perovskites are candidates in the search for lead-free halide photovoltaic absorbers. We present the application of our database to aid the discovery of new double perovskite halide photovoltaic materials, by combining the results with optical absorption and phonon stability calculations. From three distinct classes of chemistries, 11 compounds were identified as promising solar absorbers and the complex chemical trends for band gap within each of these are analyzed, to provide guidelines for the use of substitutional alloying as a means of further tuning the electronic structure. Other possible applications of the database are also discussed.

MMP-2 overexpression is strongly related to several diseases including cancer. However, none of the MMP-2 inhibitors have been marketed as drug candidates due to various adverse effects. Here, a set of sulphonyl pyrrolidines was subjected to validation of molecular modelling followed by binding mode analysis to explore the crucial structural features required for the discovery of promising MMP-2 inhibitors. This study revealed the importance of hydroxamate as a potential zinc-binding group compared to the esters. Importantly, hydrophobic and sterical substituents were found favourable at the terminal aryl moiety attached to the sulphonyl group. The binding interaction study revealed that the S1′ pocket of MMP-2 similar to 'a basketball passing through a hoop' allows the aryl moiety for proper fitting and interaction at the active site to execute potential MMP-2 inhibition. Again, the sulphonyl pyrrolidine moiety can be a good fragment necessary for MMP-2 inhibition. Moreover, some novel MMP-2 inhibitors were also reported. They showed the significance of the 3rd position substitution of the pyrrolidine ring to produce interaction inside S2′ pocket. The current study can assist in the design and development of potential MMP-2 inhibitors as effective drug candidates for the management of several diseases including cancers in the future. [ABSTRACT FROM AUTHOR]

Histone deacetylase 3 (HDAC3), a Zn2+-dependent class I HDACs, contributes to numerous disorders such as neurodegenerative disorders, diabetes, cardiovascular disease, kidney disease and several types of cancers. Therefore, the development of novel and selective HDAC3 inhibitors might be promising to combat such diseases. Here, different classification-based molecular modelling studies such as Bayesian classification, recursive partitioning (RP), SARpy and linear discriminant analysis (LDA) were conducted on a set of HDAC3 inhibitors to pinpoint essential structural requirements contributing to HDAC3 inhibition followed by molecular docking study and molecular dynamics (MD) simulation analyses. The current study revealed the importance of hydroxamate function for Zn2+ chelation as well as hydrogen bonding interaction with Tyr298 residue. The importance of hydroxamate function for higher HDAC3 inhibition was noticed in the case of Bayesian classification, recursive partitioning and SARpy models. Also, the importance of substituted thiazole ring was revealed, whereas the presence of linear alkyl groups with carboxylic acid function, any type of ester function, benzodiazepine moiety and methoxy group in the molecular structure can be detrimental to HDAC3 inhibition. Therefore, this study can aid in the design and discovery of effective novel HDAC3 inhibitors in the future. [ABSTRACT FROM AUTHOR]