Promising Schiff bases in antiviral drug design and discovery.

Emerging and re-emerging illnesses will probably present a new hazard of infectious diseases and have fostered the urge to research new antiviral agents. Most of the antiviral agents are analogs of nucleosides and only a few are non-nucleoside antiviral agents. There is quite a less percentage of marketed/clinically approved non-nucleoside antiviral medications. Schiff bases are organic compounds that possess a well-demonstrated profile against cancer, viruses, fungus, and bacteria, as well as in the management of diabetes, chemotherapy-resistant cases, and malarial infections. Schiff bases resemble aldehydes or ketones with an imine/azomethine group instead of a carbonyl ring. Schiff bases have a broad application profile not only in therapeutics/medicine but also in industrial applications. Researchers have synthesized and screened various Schiff base analogs for their antiviral potential. Some of the important heterocyclic compounds like istatin, thiosemicarbazide, quinazoline, quinoyl acetohydrazide, etc. have been used to derive novel Schiff base analogs. Keeping in view the outbreak of viral pandemics and epidemics, this manuscript compiles a review of Schiff base analogs concerning their antiviral properties and structural-activity relationship analysis.

An Explicative Review on the Progress of Quinazoline Scaffold as Bioactive Agents in the Past Decade.

In the last decade, quinazoline was one of the most explored scaffolds by researchers around the globe in medicinal chemistry. Its unique structural features provide a wide range of substitutions on nitrogen and carbonyl groups. In the current situation of COVID-19, hydroxychloroquine an antimalarial drug of the quinoline category was used for the treatment of severe infections. Various substitution patterns, hybrids, and conjugates of quinazoline have been developed and studied for various pharmacological activities like anticancer, anti-inflammatory, antimalarial, antitubercular, etc. The scaffold can be considered as a potential molecule for various pharmacological activities especially as antimicrobial and antihypertensive. The current review aims to study, physicochemical properties, chemistry, and pharmacological profile of quinazoline.

Wang-OSO3H catalyzed green synthesis of bioactive isoindolo 2,1-a quinazoline-5,11-dione derivatives: An unexpected observation

The sulphonic acid-functionalized Wang resin (Wang-OSO3H) was explored as a polymeric and recov-erable acidic catalyst for the synthesis of isoindolo[2,1-alpha]quinazoline-5,11-dione derivatives under green conditions. Thus the Wang-OSO3H catalyzed MCR of isatoic anhydride, 2-formylbenzoic acid and vari-ous amines in pure water afforded a range of desired product in good to excellent (86-94%) yield. The methodology can be performed under open air and is amenable for scale-up synthesis. The catalyst can be recovered and recycled for several times without significant loss of its catalytic activity. The unex-pected formation of 2-(1-hydroxy-3-oxoisoindolin-2-yl)benzamide derivative as observed in one case may allow the access of this class of heterocycles from the same MCR by using an appropriate amine. In silico assessment suggested that the compound 4j , a known inhibitor of TNF-alpha could be a potential ligand for SARS-CoV-2 with which it formed H-bonds through its OMe and two C = O groups. (C) 2021 Elsevier B.V. All rights reserved.

Computational Investigation on Natural Quinazoline Alkaloids as Potential Inhibitors of the Main Protease (Mpro) of SARS-CoV-2

Drug discovery is still behind in the race compared to vaccine discovery in fighting COVID-19. In this study, we have selected 41 quinazoline alkaloids from two natural product databases to create an adequate library and performed detailed computational studies against the main protease ( M pro ) of SARS-CoV-2 using two reference compounds, namely famotidine and X77. The screening of the library was carried out by blending the rigid docking and pharmacokinetic analysis that resulted in nine alkaloids as initial leads against M pro . These initial leads were further subjected to advanced flexible docking and were compared with reference compounds (famotidine and X77) for the analysis of structure-based interactions. For further selection, a second screening was carried out based on binding energies and interaction profiles that yielded three alkaloids, namely CNP0416047, 3-hydroxy anisotine and anisotine as final leads. The stereo-electronic features of lead alkaloids were further investigated through additional E-pharmacophore mapping against crystallized X77 reference compound. Additionally, the reactivity of lead alkaloids at the binding sites of the protein was estimated by measuring the electron distribution on the frontier molecular orbitals and HOMO–LUMO band energies. Finally, the stabilities of complexes between lead alkaloids with the protein were accessed extensively using robust molecular dynamics simulation through RMSD, RMSF, Rg and MM-PBSA calculation. Thus, this study identifies three natural quinazoline alkaloids as potential lead inhibitors of M pro through extensive computational analysis. This study performed a full-scale in silico investigations on natural quinazoline alkaloids against the main protease (MPro) of SARS_CoV_2 by examining forty one natural quinazoline alkaloids and identified three alkaloids (CNP0416047, 3-hydroxy anisotine and anisotine) as final lead compounds. The screening and structure-based analysis of these ligands were carried out by blending different computational techniques such as rigid docking, pharmacokinetics, flexible docking, E-pharmacophore mapping, DFT studies and MD simulations. Mostly, this study added values to quinazoline alkaloids which are fascinating natural pharmacophores and opened the possibilities of in vitro studies of these hit alkaloids in future. [ FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company 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.)

Targeting SARS-CoV-2 Polymerase with New Nucleoside Analogues.

Despite the fact that COVID-19 vaccines are already available on the market, there have not been any effective FDA-approved drugs to treat this disease. There are several already known drugs that through drug repositioning have shown an inhibitory activity against SARS-CoV-2 RNA-dependent RNA polymerase. These drugs are included in the family of nucleoside analogues. In our efforts, we synthesized a group of new nucleoside analogues, which are modified at the sugar moiety that is replaced by a quinazoline entity. Different nucleobase derivatives are used in order to increase the inhibition. Five new nucleoside analogues were evaluated with in vitro assays for targeting polymerase of SARS-CoV-2.

Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp.

Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.