Synthesis of Isatin Derivatives Using Silver Nanoparticles as Green Catalyst: Study of Molecular Docking Interactions in SARS-CoV-2 3c-Like Protease and Determination of Cytotoxic Activities of the Compounds

The coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As isatin-containing compounds exhibit several remarkable biological activities, isatin derivatives were prepared to combat the global pandemic caused by SARS-CoV-2 that is gripping the world. Herein, the synthesis of novel isatin derivatives has been reported. The cytotoxic activities of the compounds were determined using cancer cell (MCF-7) and normal cell (MCF-10A and MRC-5) lines. In silico molecular docking experiments were conducted using AutoDock Vina. We have successfully predicted the binding energies and the number of hydrogen bonds present. We have also identified the residues involved in hydrogen bond formation. The target compounds were synthesized using Schiff base following cyclization and Knoevenagel condensation reactions. We have focused on the recyclable synthesis of silver nanoparticles (AgNPs) using the extracts obtained from Dipteryx odorata. The extracts were used to reduce silver ions for the production of AgNPs. The synthesized nanoparticles exhibited excellent catalytic activities during the synthesis of isatin derivatives in ethanol. The formation of the target isatin derivatives has been confirmed using the Fourier transform-infrared (FT-IR), proton nuclear magnetic resonance (1H NMR) spectroscopy, 13C NMR spectroscopy, mass spectrometry, and elemental analysis techniques. Compound 3e was found to be the most active compound when tested against the MCF-7 cancer cell line (I C 50 = 20.5 μ M). The activity was comparable to the activities of standard doxorubicin and other compounds. In silico molecular docking experiments were conducted to study the spike protein in SARS-CoV-2 (PDB ID: 6LU7). Compound 3c exhibited high binding ability (−9.4 kcal/mol). The inhibition ability was studied using hydroxychloroquine as a standard. Results from docking studies revealed that the inhibition ability of compound 3c was higher than the inhibition abilities exhibited by other compounds. The synthesized compound 3e is a potential antiviral drug that can be used for treating the COVID-19 disease. [ABSTRACT FROM AUTHOR] Copyright of Journal of Nanomaterials is the property of Hindawi Limited 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Synthesis and Characterization of a Minophosphonate Containing Chitosan Polymer Derivatives: Investigations of Cytotoxic Activity and in Silico Study of SARS-CoV-19.

Chitosan is broadly used as a biological material since of its excellent biological activities. This work describes investigations of chitosan interaction with SARS-CoV-2, which is occupied by human respiratory epithelial cells through communication with the human angiotension-converting enzyme II (ACE2). The ß-chitosan derivatives are synthesized and characterized by FT-IR, nuclear magnetic resonance (1H and 13C NMR), mass spectrometry, X-ray diffraction, TGA, DSC, and elemental analysis. The ß-chitosan derivatives were screened for cytotoxic activity against the HepG2 and MCF-7 (breast) cancer cell lines. Compound 1h (GI50 0.02 µM) is moderately active against the HepG2 cancer cell line, and Compound 1c is highly active (GI50 0.01 µM) against the MCF-7 cancer cell line. In addition, chitosan derivatives (1a-1j) docking against the SARS coronavirus are found by in-silico docking analysis. The findings show that compound 1c exhibits notable inhibition ability compared with other compounds, with a binding energy value of -7.9 kcal/mol. Based on the molecular docking results, the chitosan analog is proposed to be an alternative antiviral agent for SARS-CoV2.

In silico molecular docking: Evaluation of coumarin based derivatives against SARS-CoV-2.

BACKGROUND: The unique anthropological coronavirus which has been titled as SARS-CoV-2 was originally arisen in late 2019 in Wuhan, China affecting respiratory infection named as COVID-19. Coronavirus is disturbing human life in an exceptional method and has converted a public health global crisis. Natural products are ahead consideration due to the huge beneficial window and effective anti-inflammatory, immunomodulatory, antioxidant and antiviral possessions. Consequently, the present study was intended to display inhibition ability of natural products coumarins and their analogues against SARS coronavirus. METHODS: The present study, aims to forecast theoretical assembly for the protease of COVID-19 and to discover advance whether this protein may assist as a target for protease inhibitors such as psoralen, bergapten, imperatorin, heraclenin, heraclenol, saxalin, oxepeucedanin, angelicin, toddacoumaquinone, and aesculetin. The docking score of these natural coumarin analogues compared with standard Hydroxychloroquine. Whereas the 3D assembly of main protease of SARS coronavirus was forecast with SWISS MODEL web server, and molecular interaction studies amongst target protein and ligands were done with AutoDock Vina software. RESULTS: The study more exposed that all the inhibitors acquired with negative dock energy against the target protein. Molecular docking investigation displayed that natural coumarin analogue toddacoumaquinone displayed a remarkable inhibition ability with the binding energy of -7.8 kcal/mol than other compounds against main protease of SARS coronavirus in intricate with α-ketoamide (PDB ID: 5N5O). The synthetic coumarin analogue (1 m) also displayed the comparable inhibition ability with a binding energy of -7.1 kcal/mol against main protease of SARS coronavirus in intricate with α-ketoamide. Keeping the overhead results of ADME and toxicity, all tested compounds were recognized as drug-like nature, passing Lipinski's "Rule of 5" with 0 violation except α-ketoamide passes Lipinski's "Rule of 5" with 1 violation MW > 500. The projected constraints are within the assortment of recognized values. CONCLUSIONS: Based upon the results of the manifold sequence alliance, natural and synthetic coumarin binding sites were preserved. The present in silico examination thus, delivers structural awareness about the protease of COVID-19 and molecular relations with some of the recognised protease inhibitors.