Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors.

Herein, we present the first experimental study of individual water-soluble fullerene derivatives proving their ability to inhibit SARS-CoV-2 in vitro. The initial screening allowed us to identify a few new compounds that have demonstrated pronounced antiviral activity with IC values as low as 390 nM and selectivity indexes reaching 214. Time-of-addition analysis and molecular docking results suggested that the viral protease and/or the spike protein are the most probable targets inhibited by the fullerene derivatives.

Evaluation of A-ring hydroxymethylene-amino- triterpenoids as inhibitors of SARS-CoV-2 spike pseudovirus and influenza H1N1.

A set of triterpene A-ring hydroxymethylene-amino-derivatives was synthesized and their antiviral activity was studied. The synthesized compounds were tested for their potential inhibition of SARS-CoV-2 pseudovirus in BHK-21-hACE2 cells and influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture. Compounds 6, 8 and 19 showed significant anti-SARS-CoV-2 pseudovirus activity with EC value of 3.

Water-Soluble Fullerene C Derivatives Are Effective Inhibitors of Influenza Virus Replication.

The influenza virus genome features a very high mutation rate leading to the rapid selection of drug-resistant strains. Due to the emergence of drug-resistant strains, there is a need for the further development of new potent antivirals against influenza with a broad activity spectrum. Thus, the search for a novel, effective broad-spectrum antiviral agent is a top priority of medical science and healthcare systems.

Synthesis and Biological Activity of Unsymmetrical Monoterpenylhetaryl Disulfides.

New unsymmetrical monoterpenylhetaryl disulfides based on heterocyclic disulfides and monoterpene thiols were synthesized for the first time in 48-88% yields. Hydrolysis of disulfides with fragments of methyl esters of 2-mercaptonicotinic acid was carried out in 73-95% yields. The obtained compounds were evaluated for antioxidant, antibacterial, antifungal activity, cytotoxicity and mutagenicity.

Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2-[1,4]benzoxazine and Evaluation of Their Antiviral Activity.

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2-[1,4]benzoxazine and its ()-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by H, F, and C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC.

New heteroanalogs of tricyclic ascidian alkaloids: synthesis and biological activity.

Heteroanalogs of ascidian alkaloids have been synthesized, and for the first time 10 different types of saturated carbo- and heteroannulated pyridones have been obtained. A new method for the formation of decahydro[1,3]oxazolo[2,3-]quinoline and octahydro-5-cyclopenta[][1,3]oxazolo[3,2-]pyridine was proposed. The synthesis of these heterocycles is based on the three-component cyclization of trifluoroacetoacetic ester and cycloketones with 1,2- and 1,3-dinucleophiles.

Water-Promoted Reaction of CArCl Compounds with Thiophenes Delivers a Family of Multifunctional Fullerene Derivatives with Selective Antiviral Properties.

Here we report a reaction of the fullerene derivatives CArCl, which enables the substitution of Cl with thiophene residues and the formation of the novel family of -symmetrical C fullerene derivatives with six functional addends CArTh. The discovered reaction provided a straightforward approach to the synthesis of previously inaccessible multifunctional water-soluble fullerene derivatives, including the compounds with antiviral activity against human immunodeficiency and influenza viruses.

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses.

To date, the 'one bug-one drug' approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus.

TfOH-Promoted Reactions of TMS-Ethers of CF-Pentenynoles with Arenes. Synthesis of CF-Substituted Pentenynes, Indenes, and Other Carbocyclic Structures.

Trimethylsilyl ethers of 1,5-diaryl-3-(trifluoromethyl)-pent-1-en-4-yn-3-oles [Ar-C≡C-C(CF)(OSiMe)-CH═CH-Ar'] in the superacid TfOH give rise to reactive conjugated CF-allylic-propargylic cations [Ar-C≡C-C(CF)-CH═CH-Ar']. These species react with arenes in the presence of 1.5 equiv of TfOH forming regio- and stereoselectively 1,1,5-triaryl-3-(trifluoromethyl)-pent-2-en-4-ynes [Ar-C≡C-C(CF)═CH-CHAr'(Ar″)] in good yields.

7-Imidazolyl-substituted 4'-methoxy and 3',4'-dimethoxy-containing polyfluoroflavones as promising antiviral agents.

A simple and convenient method for the synthesis of new methyl 2-(4-methoxyphenyl)- and 2-(3,4-dimethoxyphenyl)-4-oxo-4-polyfluorochromen-3-carboxylates as analogs of natural methoxy-containing flavones is proposed. As a result of their directed modification under basic conditions, 7-imidazolyl-substituted derivatives were obtained. In aqueous-organic medium under basic conditions, 5,6,7,8-tetrafluoro-3-(methoxycarbonyl)flavones were transformed into 6,8-difluoro-5-hydroxy-7-(1-imidazol-1-yl)-3-(methoxycarbonyl)flavones as a result of rearrangement, while 6,7,8-trifluorinated analogs underwent a rearrangement to give 6,8-difluoro-3-(hydroxyarylidene)-7-(1-imidazol-1-yl)coumarins under the same conditions.

5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines as dual inhibitors of Mycobacterium tuberculosis and influenza virus: Synthesis and evaluation.

This study describes synthesis and evaluation of novel 5-Chloro-2-thiophenyl-1,2,3-triazolylmethyldihydroquinolines 7a-o as dual inhibitors of Mycobacterium tuberculosis and influenza virus. Huisgen's [3+2] dipolar cycloaddition of 6-(azidomethyl)-5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline 5 with various alkynes 6a-o using sodium ascorbate and copper sulphate gave new dihydroquinoline-1,2,3-triazoles 7a-o in good to excellent yields. The new compounds were evaluated for in vitro antimycobacterial against M.

New HSV-1 Anti-Viral 1'-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety.

New 1'-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized.