Oxazines have brought much synthetic interest due to their extensive biological activities. These are the important category of heterocycles, which may be formally derived from benzene and its reduction products by convenient substitution of carbon (and hydrogen) atoms by nitrogen and oxygen. In the last few decades, oxazine derivatives have documented as worthy synthetic intermediates and also blessed with notable sedative, analgesic, anticonvulsant, antipyretic, antimicrobial, antitubercular, antimalarial, antioxidant, and anticancer activities. Nowadays, it is important to develop new classes of compounds with more effective mechanisms due to drug resistance activity in which the ability of drug to effectively treat disease can be reduced. The aim of the article is to collect and make a more generalized review on the synthesis of oxazine derivatives and their pharmaceutical and biological activities. We hope this review will provide ample references for the researchers concerned with azines in generally and oxazines in particular.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19 which is responsible for respiratory illness infection in humans. The virus was first identified in China in 2019 and later spread to other countries worldwide. This study aims to identify the bioactive compounds from mangosteen (Garcinia mangostana L.) as an antiviral agent via dual inhibitor mechanisms against two SARS-CoV-2 proteases through the in silico approach. The three-dimensional structure of various bioactive compounds of mangosteen from the database was examined. Furthermore, all the target compounds were analyzed for drug, antiviral activity prediction, virtual screening, molecular interactions, and threedimensional structure visualization. It aimed to determine the potential of the bioactive compounds from mangosteen that can serve as antiviral agents to fight SARS-CoV-2. Results showed that the bioactive compounds from mangosteen have the prospective to provide antiviral agents that contradict the virus via dual inhibitory mechanisms. In summary, the binding of the various bioactive compounds from mangosteen results in low binding energy and is expected to have the ability to induce any activity of the target protein binding reaction. Therefore, it allows various bioactive compounds from mangosteen to act as dual inhibitory mechanisms for COVID-19 infection.

Background Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET) from a compound is essential, especially for modified novel compounds. Previous research has successfully designed several modified compounds of 5-O-benzoyl derivatives from pinostrobin, a flavanone that has cytotoxic activity. This study aims to describe the properties of ADMET from the 5-O-benzoylpinostrobin derivative. Methods Prediction of the properties of ADMET was carried out using three web servers consisting of SwissADME, pkCSM, and ProTox-II. The observed parameters are divided into ADMET parameters. Results In general, absorption parameters indicate that the 5-O-benzoylpinostrobin derivative has lower water solubility than the parent pinostrobin. Distribution parameters show mixed results for distribution through the blood-brain barrier. Metabolism parameters showed different results with generally inhibitory activity shown in CYP2C19, CYP2C9, and CYP3A4. The excretion parameters showed a higher total clearance than pinostrobin except in the trifluoromethyl derivative. The toxicity parameters showed both pinostrobin and the 5-O-benzoylpinostrobin derivatives, including the class IV toxicity category with the lowest LD50 value indicated by the nitro derivative of 1500, with the possible target of the androgen receptor and prostaglandin G/H synthase 1. Conclusions Overall, the 5-O-benzoylpinostrobin derivative has the predicted ADMET profile that is relatively similar to pinostrobin, with the most noticeable difference being shown in the absorption parameters where all 5-O-benzoylpinostrobin derivatives have lower water solubility than pinostrobin.

Objectives: This study aims to find the relationship between artemisinins and neuraminidase (NA) with molecular docking study and also to determine the most potent NA inhibitor from artemisinin and derivatives.Methods: All ligands were sketched and optimized using Gaussian 03W with Hartree-Fock method basis sets 6-311G. Molecular docking was performed using AutoDock 4.2.3 toward NA in complexes with oseltamivir as co-crystal ligand. The main parameters used were the free energy of binding (∆G) and dissociation constant (K i ) as affinity marker.Results: Artesunate provided most negative free ∆G and lowest K i toward NA with −9.55 kcal/mol and 100.66 nM, respectively. Artesunate shows higher affinity than oseltamivir with interactions between artesunate and amino acids at position 246 had important influences on artesunate affinity toward NA from H5N1. Conclusion:In silico molecular docking results indicated that artesunate could be considered as NA inhibitor and should be potential to be developed as anti-influenza particularly to H5N1 with oseltamivir resistance.

Background: COVID-19, a global pandemic caused by SARS-CoV-2 infection, has led researchers around the world to search for therapeutic agents for treatment of the disease. The main protease (M Pro ) of SARS-CoV-2 is one of the potential targets in the development of new drug compounds for the disease. Some known drugs such as chloroquine and remdesivir have been repurposed for treatment of COVID-19, although the the mechanism of action of these compounds is still unknown. In addition to these known drugs, new drug compounds such as 5-O-benzoylpinostrobin derivatives are also potentially used as SARS-CoV-2 M Pro inhibitors. This study aims to determine the potential of 5-O-benzoylpinostrobin derivatives as SARS-CoV-2 M Pro inhibitors, compared with several other compounds used in COVID-19 therapy. Methods: In silico study was carried out by molecular docking of 5-O-benzoylpinostrobin derivatives using Autodock Vina on two SARS-CoV-2 M Pro receptors with PDB IDs of 5R84 and 6LU7. The free energy of binding was calculated and the the interactions of each ligand were analyzed and compared with reference ligand. Results: Three 5-O-benzoylpinostrobin derivatives each with fluoro, tertiary butyl, and trifluoromethyl substituents at 4-position of benzoyl group showed the lowest free energy of binding value and the highest similarity of ligand-receptor interactions with co-crystalized ligands. These three compounds even exhibited promising results in comparison with other reference ligands such as remdesivir and indinavir. Conclusion:The results of this investigation anticipate that some 5-O-benzoylpinostrobin derivatives have the potential as SARS-CoV-2 M Pro inhibitors.

Pyrazoline and its derivatives have numerous prominent pharmacological effects. Focusing on its anti-viral property, we have designed and synthesized three novel pyrazoline derivatives ( A1–A3 ) through one-pot three components and characterized them using different spectroscopic techniques (FT-IR, 1 H NMR, 13 C NMR, and UV). These compounds were evaluated against SARS-CoV-2 main protease utilizing in-silico molecular docking studies. The docking results displayed good inhibitory activity of the synthesized compounds. Among them, compound A2 was the most active against targeted protein. The drug-likeness and ADMET properties were predicted to have varied profiles but could still be developed, especially A2 . DFT/TD-DFT calculations through B3LYP/6-311G++ level of theory were applied to provide comparable theoretical data along with MEP map and electronic energy gap of HOMO → LUMO. Supplementary Information The online version contains supplementary material available at 10.1007/s11164-022-04831-5.