Synthesis, Characterization and Molecular Docking of New Nucleosides and Schiff Bases Derived from Ampyrone as Antiviral Agents to Contain the COVID-19 Virus

A new series of nucleoside derivatives was prepared from the reaction of 4-aminoantipyrene with different sugar moieties. In addition, ampyrone's reaction with different aromatic aldehydes gave the corresponding Schiff base derivatives, which were also synthesized. Both molecular docking and in vitro antiviral activities at different concentrations of different synthesized compounds against SARS-CoV-2 were screened. All newly synthesized compounds were characterized on the basis of IR, 1H NMR and 13C NMR spectral data and physical data. The compounds were screened for potential cytotoxic activities. The molecular docking analysis showed that compounds 6b, 6e, 6c, 6f and 6d exhibited relatively higher binding energies (−8.1, −8.1, −8.3, −8.4 and −8.7 kcal/mol, respectively) compared to all the other compounds. However, the different compounds did not show any promising in vitro antiviral activities against SARS-CoV-2.

Synthesis, DFT and In Silico Anti-COVID Evaluation of Novel Tetrazole Analogues

A new series of 3-aryl/heteroaryl-2-(1H-tetrazol-5-yl) acrylamides have been synthesized through catalyst-free, one-pot cascade reactions, utilizing click chemistry approach and evaluated for their anti-COVID activities against two proteins in silico. The structural properties of the synthesized molecules were evaluated based on DFT calculations. Total energy of the synthesized tetrazole compounds were obtained through computational analysis which indicate the high stability of the synthesized compounds. The Frontier Molecular Orbitals (FMO) and associated energies and molecular electrostatic potential (MEP) surfaces were generated for the compounds. Spectral analysis by DFT gave additional evidence to the structural properties of the synthesized molecules. All tetrazole analogues come under good ADMET data as they followed the standard value for ADMET parameters. Docking studies offered evidence of the molecules displaying excellent biological properties as an anti-Covid drug. Compound 4 g exhibited excellent anti-COVID-19 properties with four hydrogen binding interactions with amino acids GLN 2.486 Å, GLN 2.436 Å, THR 2.186 Å and HSD 2.468 Å with good full-fitness score (–1189.12) and DeltaG (–7.19). Similarly, compound 4d shown potent activity against anti-COVID-19 mutant protein (PDB: 3K7H) with three hydrogen binding interactions, i.e., SER 2.274 Å, GLU 1.758 Å and GLU 1.853 Å with full-fitness score of –786.60) and DeltaG (–6.85). The result of these studies revealed that the compounds have the potential to become lead molecules in the drug discovery process.

Synthesis, E-pharmacophore, Molecular Docking Studies with SARS-CoV-2 Protease, Their Biological Properties and DFT Calculation of Some New Indolo[3,2-c]Isoquinoiline Hybrids

A series of novel indolo[3,2-c]isoquinoline hybrids derivatives were synthesized. On the basis of spectroscopic and analytical data, the structures of newly synthesized compounds were determined. They were further evaluated for their in vitro antimicrobial, antioxidant anticancer and anti-TB activities. Results reveal that compounds 4a and 5a displayed better potency against all bacterial strains and compound 3b showed significant antifungal action against all fungi tested. Compound 4b display excellent antioxidant capability. Compounds 3a, 4a, and 5a bearing chloro on indolo[3,2-c]isoquinoline ring were found have higher potency against all cancer cell lines. Compound 5b displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC 0.12 μg/mL. Consequently, a five-point e-pharmacophore model (AADDR) was built. Docking studies displayed that compounds 2a, 2b, 3a, 4b, and 4c exhibited stronger interactions and higher binding affinity toward Glu166, Gln189, and His41, which are critical amino acid residues that play a significant role in PDB: 7D1M (SARS-CoV-2 Mpro) through hydrogen bonding, hydrophobic and π-π interactions. Further, frontier molecular orbitals studies were executed to understand their orbital energies and HOMO-LUMO lowest energy gap is 8.39 eV shown by compound 5a.

The Chloroquine Story in the First Year of the COVID-19 Pandemic

The emergence of COVID-19 has caused worldwide concern due to its high infectivity and mortality. Research groups around the world have prioritised drug development against COVID-19. Repurposing of already approved drugs, including the antimalarial drug chloroquine, has attracted considerable attention. The aim of this article is to (i) provide an overview of the recent chemical methods used to synthesise chloroquine and hydroxychloroquine, and (ii) provide insight into the data collected in 2020 on their efficacy against COVID-19. Unfortunately, the promising early results have not been confirmed and a clear and unambiguous conclusion on their clinical efficacy has not yet been drawn. (English) [ FROM AUTHOR] Pojava COVIDA-19 uzrokovala je globalnu zabrinutost zbog visoke zaraznosti i mortaliteta. Stoga je razvoj lijekova protiv COVIDA-19 postao prioritet istraživačkim skupinama diljem svijeta. Pri tom je posebnu pozornost privukla moguća prenamjena prethodno odobrenih lijekova, uključujući i antimalarijski lijek klorokin. Cilj ovog rada je (i) prikazati pregled recentnih kemijskih metoda primijenjenih za sintezu klorokina i hidroksiklorokina te (ii) dati uvid u podatke o njihovoj učinkovitosti protiv COVIDA-19 prikupljene tijekom 2020. Nažalost, početni obećavajući rezultati nisu potvrđeni, a jasni i nedvosmisleni zaključci o kliničkoj učinkovitosti klorokina i hidroksiklorokina još nisu postignuti. (Croatian) [ FROM AUTHOR] Copyright of Kemija u Industriji is the property of Croatian Society of Chemical Engineers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

New Achievements for the Treatment of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) constitutes a heterogeneous group of malignancies that are often aggressive and associated with a poor prognosis. The development of new TNBC treatment strategies has become an urgent clinical need. Diagnosis and subtyping of TNBC are essential to establish alternative treatments and targeted therapies for every TNBC patient. Chemotherapy, particularly with anthracycline and taxanes, remains the backbone for medical management for both early and metastatic TNBC. More recently, immune checkpoint inhibitors and targeted therapy have revolutionized cancer treatment. Included in the different strategies studied for TNBC treatment is drug repurposing. Despite the numerous medications available, numerous studies in medicinal chemistry are still aimed at the synthesis of new compounds in order to find new antiproliferative agents capable of treating TNBC. Additionally, some supplemental micronutrients, nutraceuticals and functional foods can potentially reduce the risk of developing cancer or can retard the rate of growth and metastases of established malignant diseases. Finally, nanotechnology in medicine, termed nanomedicines, introduces nanoparticles of variable chemistry and architecture for cancer treatment. This review highlights the most recent studies in search of new therapies for the treatment of TNBC, along with nutraceuticals and repositioning of drugs.

Biofuel Generation from Potato Peel Waste: Current State and Prospects

Growing environmental concerns, increased population, and the need to meet the diversification of the source of global energy have led to increased demand for biofuels. However, the high cost of raw materials for biofuels production has continued to slow down the acceptability, universal accessibility, and affordability of biofuels. The cost of feedstock and catalysts constitutes a major component of the production cost of biofuels. Potato is one of the most commonly consumed food crops among various populations due to its rich nutritional, health, and industrial benefits. In the current study, the application of potato peel waste (PPW) for biofuel production was interrogated. The present state of the conversion of PPW to bioethanol and biogas, through various techniques, to meet the ever-growing demand for renewable fuels was reviewed. To satisfy the escalating demand for biohydrogen for various applications, the prospects for the synthesis of biohydrogen from PPW were proposed. Additionally, there is the potential to convert PPW to low-cost, ecologically friendly, and biodegradable bio-based catalysts to replace commercial catalysts. The information provided in this review will enrich scholarship and open a new vista in the utilization of PPW. More focused investigations are required to unravel more avenues for the utilization of PPW as a low-cost and readily available catalyst and feedstock for biofuel synthesis. The application of PPW for biofuel application will reduce the pump price of biofuels, ensure the appropriate disposal of waste, and contribute towards environmental cleanliness.

Chiral Molecules: Properties, Synthesis and Analysis

In this paper, the authors describe a set of dynamic chromatography experiments on chiral HPLC columns, and in the range from room temperature to −50 °C for four 1,4-benzodiazepines, extracting the data for the best analytical conditions for their enantiomeric separation. [...]I want to express my great appreciation for the efficient assistance provided to me by Amelia Sun and the Editorial Office of Symmetry. Abbreviations PXRD: powder X-ray diffraction;ESI: electrospray ionization;HPLC: high-performance liquid chromatography;DFT: density functional theory;VCD: vibrational circular dichroism;ECD: electronic circular dichroism;CD: circular dichroism.

(±)-2-(2-Fluoro-[1,1′-biphenyl]-4-yl)-N-(1-phenylpropan-2-yl)propanamide

2-(2-fluoro-[1,1′-biphenyl]-4-yl)-N-(1-phenylpropan-2-yl)propanamide was synthesized by a reaction between amphetamine and flurbiprofen in high yields. The newly obtained hybrid molecule was fully analyzed and characterized via 1H, 13C, UV, IR, HPLC, and mass spectral data.

Chemical and chemoenzymatic stereoselective synthesis of β-nucleosides and their analogues

β-Nucleosides are fundamental building blocks of biological systems and are widely used as therapeutic agents for the treatment of cancer and viral infections, among others. In the last two years, nucleoside analogues have been investigated with renewed urgency in the search for agents that are effective against SARS-CoV-2, the cause of the ongoing global pandemic of COVID-19. This has resulted in an explosion of activities in the field of β-nucleoside synthesis. This review summarizes the historical perspective and the recent advances in the stereoselective synthesis of β-nucleosides and their analogues. The synthetic strategies to obtain β-nucleosides can be divided into three categories: (1) N-glycosylation;(2) intramolecular sugar ring formation;and (3) enzymatic transglycosylation.

Quantitative Efficacy of Common Virucidal Disinfectants Against Viral Surrogates on Porous and Nonporous Surfaces

The objectives of this effort were threefold: (a) compare Ebola virus (EBOV) with a potential surrogate, the enveloped vaccinia virus (VACV), for susceptibility to disinfectants;(b) generate efficacy data for five U.S. Environmental Protection Agency-registered virucidal chemicals and one experimental disinfectant, 5 percent vinegar, against VACV;and (c) compare the efficacy of three chemicals against Phi 6 (a bacteriophage surrogate for EBOV) and VACV. The Organisation for Economic Co-operation and Development (OECD) method was adopted for efficacy evaluations. Of the three test viruses, VACV was found be the most persistent virus. Of six disinfectants, Peridox disinfectant (Contec;Spartanburg, SC) was most effective against all three viruses. Bioxy-S sanitizer (Atomes, Inc.;Quebec, Canada) was effective against all three viruses. The other four disinfectants were not very effective against VACV. Peridox disinfectant, 0.2 percent peracetic acid (PAA), and 0.5 percent bleach were effective against Phi 6 in the absence of blood. In the presence of blood (dried and wet), both Peridox disinfectant and PAA were equally effective against Phi 6. VACV is recommended as a potential surrogate for EBOV. More importantly, this study highlights that the DoD must generate its own database on efficacy of disinfectants for military surfaces to select effective chemicals in the event of a pandemic resulting from an infectious virus.

COVID 19: A Selected Bibliography

This is a selected bibliography on the topic of COVID-19. This bibliography includes topics such as COVID-19 case studies, vaccines, studies on SARS-CoV-2, personal protective equipment, drugs to treat COVID-19, and more.

Development of Molecular Chaperone Inhibitors for (Re)Sensitization of CRPC to Enzalutamide and Abiraterone and to Synergize with Metabolic Inhibitors

Objective: (1) Improve the solubility and pharmacodynamic properties of previously identified Hsp40 and Hsp70 inhibitors in preparation for Phase I clinical evaluation in CRPC patients. (2) Determine whether these chaperone inhibitors sensitize resistant CRPC to Enz and/or Abi and, if so, by what mechanism(s). (3) Increase our understanding of the role of these chaperones in regulating AR-driven metabolic deregulation, with the goal of identifying novel synergistic combinatorial approaches to target CRPC. Impact: By identifying a chaperone-based approach to inhibit or reverse CRPC resistance to Enz and/or Abi, the current research proposal addresses the dual 2018 PCRP Overarching Challenges of (1) developing treatments that improve the outcomes for men with lethal prostate cancer and (2) better defining the biology of lethal prostate cancer to reduce death. Further, consistent with the mandate of the PCRP Impact Award, a key goal of our research strategy is to position the program for first-in-human clinical evaluation of one or more of these chaperone inhibitors within 5 years after completion of this Award.

Overview of Methods for Large-Scale RNA Synthesis

In recent years, it has become clear that RNA molecules are involved in almost all vital cellular processes and pathogenesis of human disorders. The functional diversity of RNA comes from its structural richness. Although composed of only four nucleotides, RNA molecules present a plethora of secondary and tertiary structures critical for intra and intermolecular contacts with other RNAs and ligands (proteins, small metabolites, etc.). In order to fully understand RNA function it is necessary to define its spatial structure. Crystallography, nuclear magnetic resonance and cryogenic electron microscopy have demonstrated considerable success in determining the structures of biologically important RNA molecules. However, these powerful methods require large amounts of sample. Despite their limitations, chemical synthesis and in vitro transcription are usually employed to obtain milligram quantities of RNA for structural studies, delivering simple and effective methods for large-scale production of homogenous samples. The aim of this paper is to provide an overview of methods for large-scale RNA synthesis with emphasis on chemical synthesis and in vitro transcription. We also present our own results of testing the efficiency of these approaches in order to adapt the material acquisition strategy depending on the desired RNA construct.