Atomistic De-novo Inhibitor Generation-Guided Drug Repurposing for SARS-CoV-2 Spike Protein with Free-Energy Validation by Well-Tempered Metadynamics

Computational drug design is increasingly becoming important with new and unforeseen diseases like COVID-19. In this study, we present a new computational de novo drug design and repurposing method and applied it to find plausible drug candidates for the receptor binding domain (RBD) of SARS-CoV-2 (COVID-19). Our study comprises three steps: atom-by-atom generation of new molecules around a receptor, structural similarity mapping to existing approved and investigational drugs, and validation of their binding strengths to the viral spike proteins based on rigorous all-atom, explicit-water well-tempered metadynamics free energy calculations. By choosing the receptor binding domain of the viral spike protein, we showed that some of our new molecules and some of the repurposable drugs have stronger binding to RBD than hACE2. To validate our approach, we also calculated the free energy of hACE2 and RBD, and found it to be in an excellent agreement with experiments. These pool of drugs will allow strategic repurposing against COVID-19 for a particular prevailing conditions.     

Solubility of Anthraquinone Derivatives in Supercritical Carbon Dioxide: New Correlations

Solubility of several anthraquinone derivatives in supercritical carbon dioxide was readily available in the literature, but correcting ability of the existing models was poor. Therefore, in this work, two new models have been developed for better correlation based on solid–liquid phase equilibria. The new model has five adjustable parameters correlating the solubility isotherms as a function of temperature. The accuracy of the proposed models was evaluated by correlating 25 binary systems. The proposed models observed provide the best overall correlations. The overall deviation between the experimental and the correlated results was less than 11.46% in averaged absolute relative deviation (AARD). Moreover, exiting solubility models were also evaluated for all the compounds for the comparison purpose.     

Synthesis of N-substituted-2-aminobenzothiazoles using nano copper oxide as a recyclable catalyst under ligand-free conditions in reusable PEG-400 medium

A simple and practical method for the synthesis of N-substituted-2-aminobenzothiazoles via a crosscoupling reaction of 2-iodo anilines with isothiocyanates is envisaged using nano copper oxide as a recyclable catalyst and Cs2CO3as a base in PEG-400,as a bio-degradable,reusable,inexpensive and nontoxic reaction medium,under ligand-free conditions.The present tandem process underlines environmental acceptability to access a wide range of N-substituted-2-aminobenzothiazoles in good to excellent yields.     

One-pot green synthesis of novel 5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine derivatives with eco-friendly biodegradable eggshell powder as efficacious catalyst

Research on Chemical Intermediates - An eco-friendly and efficient green protocol is developed for the synthesis of sixteen pyrazolo-phthalazine derivatives (5a–p) by using...     

Synthesis of spirooxindolocarbamates based on Betti reaction: antibacterial,antifungal and antioxidant activities

Molecular Diversity - A series of new spirooxindolocarbamates 4a–l and 6a–d were synthesized by using the Betti reaction. All the target compounds were well characterized by IR, NMR and...     

Oxidative amidation of benzyl alcohols with amino acid esters mediated by N-hydroxysuccinimide/phenyliodine diacetate

A simple protocol involving metal-free oxidative amidation of benzyl alcohols with amino acid esters has been presented. The amidation proceeds in a radical pathway unlike in conventional metal-mediated extrusion of dihydrogen. The method is advantageous in terms of metal-free conditions, nonexpensive commercial starting substrates. Also various substituents in the starting materials are tolerated and sterically hindered amino acid side chains could provide good yields of amide products.     

A short and concise route to total synthesis of Dendrodolide L

A short and efficient method for the stereoselective synthesis of Dendrodolide L has been developed from inexpensive and commercially available starting material. This convergent synthesis utilizes Jacobsen kinetic resolution, regioselective ring-opening of epoxide and Yamaguchi macrolactonization as key steps.