Picturing beach erosion and deposition trends using PSInSAR: an example from the non-barred southern west coast of India

Coastal dynamics can rapidly alter beach morphology. In some places, such as the non-barred southern west coast of India, studying changes to beach morphology is a relatively arduous task. Persistent Scatterer Interferometric Synthetic Aperture Radar (PSInSAR), a remote sensing technique that utilizes stacks of radar images for accurate long-term monitoring of ground features, allows for detailed observations of coastal morphodynamics. Twenty-two single look complex (SLC) synthetic aperture radar (SAR) Sentinel-1A images, acquired from 4 March 2016 to 3 June 2017, are used to monitor geomorphological processes such as coastal erosion and deposition. Ground deformation measurements from PSInSAR processing shows the coast stretching?~?70 km between Thaickal and Munambam is highly dynamic, characterized by phases of erosion and deposition. The highest negative displacement of ? 24.9 mm at Thaickal versus the?+?7.6 mm at Chellanam in the north show the co-existing milieus of erosion and deposition. PSInSAR results concur with corresponding Google Earth images. In addition, beach sediment texture and scanning electron microscope grain micro-texture in the beach segment further corroborate temporal phases of erosion and deposition. Two locations are identified as typical erosional sites, while one location typified deposition. Erosion and deposition or rebuilding of beaches, usually correspond respectively with the onset and offset of SW monsoon wave climate in the Arabian Sea. When zones of deposition are mainly located in the proximity of river and/or lake inlets, stretches characterized by erosion are distal to inlets. Linear regression analyses of displacement–time series plots were used to identify general erosion or depositional regimes along beach segments. Results from this study illustrate how PSInSAR is a capable and reliable processing tool for monitoring temporal phases of coastal morpho-dynamics.

     

Synthesis and Characterization of Novel 2-Amino-Chromene-Nitriles that Target Bcl-2 in Acute Myeloid Leukemia Cell Lines

The anti-apoptotic protein Bcl-2 is a well-known and attractive therapeutic target for cancer. In the present study the solution-phase T3P-DMSO mediated efficient synthesis of 2-amino-chromene-3-carbonitriles from alcohols, malanonitrile and phenols is reported. These novel 2-amino-chromene-3-carbonitriles showed cytotoxicity in human acute myeloid leukemia (AML) cell lines. Compound 4g was found to be the most bioactive, decreasing growth and increasing apoptosis of AML cells. Moreover, compound 4g (at a concentration of 5 µM) increased the G2/M and sub-G1 (apoptosis) phases of AML cells. The AML cells treated with compound 4g exhibited decreased levels of Bcl-2 and increased levels of caspase-9. In silico molecular interaction analysis showed that compound 4g shared a similar global binding motif with navitoclax (another small molecule that binds Bcl-2), however compound 4g occupies a smaller volume within the P2 hot spot of Bcl-2. The intermolecular π-stacking interaction, direct electrostatic interactions, and docking energy predicted for 4g in complex with Bcl-2 suggest a strong affinity of the complex, rendering 4g as a promising Bcl-2 inhibitor for evaluation as a new anticancer agent.     

Novel Synthetic Biscoumarins Target Tumor Necrosis Factor-α in Hepatocellular Carcinoma in Vitro and in Vivo

TNF is a pleotropic cytokine known to be involved in the progression of several pro-inflammatory disorders. Many therapeutic agents have been designed to counteract the effect of TNF in rheumatoid arthritis as well as a number of cancers. In the present study we have synthesized and evaluated the anti-cancer activity of novel biscoumarins in vitro and in vivo. Among new compounds, BIHC was found to be the most cytotoxic agent against the HepG2 cell line while exhibiting less toxicity toward normal hepatocytes. Furthermore, BIHC inhibited the proliferation of various hepatocellular carcinoma (HCC) cells in a dose- and time-dependent manner. Subsequently, using in silico target prediction, BIHC was predicted as a TNF blocker. Experimental validation was able to confirm this hypothesis, where BIHC could significantly inhibit the recombinant mouse TNF-α binding to its antibody with an IC₅₀ of 16.5 μm. Furthermore, in silico docking suggested a binding mode of BIHC similar to a ligand known to disrupt the native, trimeric structure of TNF, and also validated with molecular dynamics simulations. Moreover, we have demonstrated the down-regulation of p65 phosphorylation and other NF-κB-regulated gene products upon BIHC treatment, and on the phenotypic level the compound shows inhibition of CXCL12-induced invasion of HepG2 cells. Also, we demonstrate that BIHC inhibits infiltration of macrophages to the peritoneal cavity and suppresses the activity of TNF-α in vivo in mice primed with thioglycollate broth and lipopolysaccharide. We comprehensively validated the TNF-α inhibitory efficacy of BIHC in an inflammatory bowel disease mice model.     

Triazole‐Pyridine Dicarbonitrile Targets Phosphodiesterase 4 to Induce Cytotoxicity in Lung Carcinoma Cells

Phosphodiesterase 4 (PDE4) is a key enzyme involved in the hydrolysis of cyclic adenosine monophosphate (cAMP) and widely expressed in several types of cancers. The inhibition of PDE4 results in an increased concentration of intracellular cAMP levels that imparts the anti‐inflammatory response in the target cells. In the present report, two series of triazolo‐pyridine dicarbonitriles and substituted dihydropyridine dicarbonitriles were synthesized using green protocol (TBAB in refluxed water). We next evaluated the title compounds for their cytotoxicity towards lung cancer (A549) cells and identified 7′‐[4‐(methylsulfonyl)phenyl]‐5′‐oxo‐1′,5′‐dihydrospiro[cyclohexane‐1,2′‐[1,2,4]triazolo[1,5‐a]pyridine]‐6′,8′‐dicarbonitrile ( 5h ) and 7′‐(1‐methyl‐1H‐imidazol‐2‐yl)‐5′‐oxo‐1′,5′‐dihydrospiro[cyclohexane‐1,2′‐[1,2,4]triazolo[1,5‐a]pyridine]‐6′,8′‐dicarbonitrile ( 5j ) as lead analogs with the IC₅₀ values of 15.2 and 24.1 μm , respectively. Furthermore, all the new compounds were tested for PDE4 inhibitory activity and 5j showed relatively good inhibitory activity towards PDE4 with inhibition of 50.9 % at 10 μm . In silico analysis demonstrated the favorable interaction of the title compounds with the target enzyme. Taken together, the present study introduces a new scaffold for the development of novel PDE4 inhibitors to fight against inflammatory diseases.