No abstract

Dengue is a prominent viral disease transmitted by mosquitoes to humans that affects mainly tropical and subtropical countries worldwide. The global spread of dengue virus (DENV) is mainly occurred by Aedes aegypti and Aedes albopictus mosquitoes. The dengue virus serotypes-2 (DENV-2) is a widely prevalent serotype of DENV, that causes the hemorrhagic fever and bleeding in the mucosa, which can be fatal. In the life cycle of DENV-2, a structural capsid (DENV-2 C) protein forms the nucleocapsid assembly and bind to the viral progeny RNA. For DENV-2 maturation, the nucleocapsid is a vital component. We used virtual ligand screening to filter out the best in-house synthesized acridinedione analogs (DSPD molecules) that could efficiently bind to DENV-2 C protein. The molecular docking and dynamics simulations studies were performed to analyze the effect of DSPD molecules on DENV-2 C protein after binding. Our findings showed that DSPD molecules strongly interacted with DENV-2 C protein, as evident from molecular interactions and several time-dependent molecular dynamics-driven analyses. Moreover, this study was also supported by the thermodynamic binding free energy and steered molecular dynamics simulations. Therefore, we intend to suggest that the DSPD3 molecule could be used as a potential therapeutic molecule against dengue complications as compared to the cocrystallized inhibitor ST-148. However, further studies are required to demonstrate the ability of DSPD3 to induce DENV-2 C tetramer formation.

Polyionic Amberlite resin formate (ARF), derived from commercially available Amberlite resin chloride by simple rinsing with aqueous formic acid, could be soaked with palladium(0) from palladium salts, the formate counteranion being the reducing source. The resulting Amberlite resin formate supported with palladium(0), ARF-Pd, showed excellent catalytic activity in Heck, Suzuki-Miyaura, and Sonogashira couplings with a range of substrates. The catalyst may be recovered easily and quantitatively without leaching and recycled; it was tested for five runs without any significant loss of activity.Transition-metal-catalyzed organic reactions constitute the central part of contemporary organic synthesis. In particular, palladium-catalyzed C-C bond-forming processes are foremost in the arena of organic process development. 1 The Heck, Suzuki-Miyaura, and Sonogashira reactions are excellent tools for C-C coupling reactions between aryl halides or triflates and suitable partners. 1d Over the last decade, commendable research has been performed and significant developments have been made and practical methodologies have been established. Widespread uses of palladium-catalyzed coupling reactions are found in modern organic synthesis, because the resulting coupled products often find good applications in the preparation of materials, 2 pharmaceuticals, 3 and other bioactive compounds. 4Since the common facet of these C-C coupling reactions is the palladium, which acts as the catalyst, numerous attempts have been made to employ it as either a soluble homogeneous 5 or an immobilized heterogeneous catalyst. 6 Soluble homogeneous palladium catalysts are found to have significant activity in various coupling reactions, but there are drawbacks, such as less active or inactive colloidal species, the catalyst is unrecoverable, the possibility of product contamination, and cost, that are often encountered in the course of such reactions. 7 Consequently, several approaches have been explored utilizing various immobilization techniques on solid or colloidal supports, 8 with the aim of efficient recovery and reuse of the active catalysts. The major thrust for achieving success in designing and developing polymer-supported metal catalysts broadly include: improved stability within the polymer matrix, increased selectivity for reactions, enhanced regioselectivity, phosphine-free, reusable for several runs, and superior asymmetric induction due to sitespecific chiral catalysts. In the past few years, several attempts have been made to surmount the problems pertaining to high reaction temperatures, separation of pure products, and recovery and reuse of palladium complexes by the use of heterogeneous palladium systems. Palladium-on-carbon, 9a carbon nanotubes, 9b and palladium on different metal oxides, 9 silica gel and modified silica gel, 10 fluorous silica, 10e,f zeolites, 11 molecular sieves, 12 hydrotalcite, 13 and sepiolites 14 were found to be suitable catalysts for some reactions. Several groups have examined the use of polymer/dend...

No abstract

Transition metals have been an indispensable component of modern catalysis and among these palladium is the top‐ranked choice of chemists as a catalyst. After the several important developments of palladium catalysed C−C cross‐coupling reactions, carbonylative transformations have been realised as an attractive post modification of these reactions. Carbonylative Suzuki‐Miyaura coupling reaction is among such transformations for direct incorporation of CO fragment for the preparation of biaryl or aryl/alkyl ketones via transition‐metal catalysis. Ketone functionality is basically a valuable building block having huge pharmaceutical and agrochemical applications. Moreover, carbonylative Suzuki‐Miyaura coupling is also used in the synthesis of various natural bioactive molecules through the direct joining of molecular fragments via CO bridge. In this review, the past decade developments in the carbonylative Suzuki‐Miyaura coupling reactions are documented in detail with modern approaches in transition‐metal catalysis.

Background Non-structural protein 1 (Nsp1), a virulence agent of SARS-CoV-2, has emerged as an important target for drug discovery. Nsp1 shuts down the host gene function by associating with the 40S ribosomal subunit. Methods Molecular interactions, drug-likeness, physiochemical property predictions, and robust molecular dynamics (MD) simulations were employed to discover novel Nsp1 inhibitors. In this study, we evaluated a series of molecules based on the plant ( Cedrus deodara ) derived α,β,γ -Himachalenes scaffolds. Results The results obtained from estimated affinity and ligand efficiency suggested that BCH10, BCH15, BCH16, and BCH17 could act as potential inhibitors of Nsp1. Moreover, MD simulations comprising various MD driven time-dependent analyses and thermodynamic free energy calculations also suggested stable protein-ligand complexes and strong interactions with the binding site. Furthermore, the selected molecules passed drug likeliness parameters and the physiochemical property analysis showed acceptable bioactivity scores. Conclusion The structural parameters of dynamic simulations revealed that the reported molecules could act as lead compounds against SARS-CoV-2 Nsp1 protein.

No abstract

No abstract