No abstract

In this study, the inhibitory potency of four adamantlyisothiourea derivatives (compounds 1 [4-bromobenzyl (Z)-N'-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate], 2 [3,5-bis(trifluoromethyl)benzyl (Z)-N'-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidate], 3 [4-bromobenzyl (Z)-N-(adamantan-1-yl)morpholine-4-carbothioimidate] and 4 [3,5-bis (trifluoromethyl)benzyl (Z)-N-(adamantan-1-yl)morpholine-4carbothioimidate]) was evaluated against SARS-CoV-2 targeted proteins. The investigated compounds 1-4 possess a similar structure to opaganib, which is used in studies like a potential drug for COVID-19 treatment. Since examined adamantlyisothiourea derivatives (1-4) shown broad-spectrum of antibacterial activity and significant in vitro cytotoxic effects against five human tumor cell lines and shown similarity in structure with opaganib, it was of interest to study their inhibitory potency toward some SARS-CoV-2 proteins such as SARS-CoV-2 main protease M pro and mutation of SARS-CoV-2 Spike (S) Protein D614G. The inhibitory potency of studied compounds is examined using molecular docking and molecular dynamic simulations. The results of molecular docking simulations indicate compound 1 as the most prominent candidate of inhibition of SARS-CoV-2 main protease M pro (~G bind = 11.24 kcal/mol), while almost the same inhibition potency of all studied compounds is exhibited toward D614G. Regarding the results obtained by molecular dynamic simulations, compounds 1 and 4 possess similar inhibitory potency toward SARS-CoV-2 main protease M pro as opaganib (~G bind �40 kcal/mol).

No abstract

The phenolic compounds, which are rich in red wine, have gained considerable attention due to their antioxidant potential. Selected Serbian wines were analyzed for their antioxidant activity by DPPH test and the total content of phenolic compounds was determined by employing the Folin-Ciocalteu colorimetric method. The major polyphenols were determined by HPLC. The antioxidant activity was correlated with the amount of specific polyphenols (gallic acid, caffeic acid, catechin, epicatechin, myricetin, and kaempferol) by quantitative structure-activity relationship. The origin of the antioxidant potential of wines was discussed based on the individual activity of identified polyphenols and theoretical calculations (at APFD/6-311++G(d,p) level of theory). The thermodynamic parameters of free radical scavenging activity and reactivity towards DPPH • , HO • , and HOO • were explained with special emphasis on the effect of structure and intramolecular interactions in polyphenols. Based on the presented data, the positive effects of selected Serbian wines on humane health and biologically relevant free radicals are concluded.

Within this study, the antioxidant capacity of bergaptol (BER) and xanthotoxol (XAN) in a nonpolar environment (benzene) was investigated against the reference standard trolox (Tx). The ability to inactivate HO• radicals from the kinetic aspect was examined through hydrogen atom transfer (HAT), single-electron transfer–proton transfer (SET-PT), sequential proton loss electron transfer (SPLET) and radical adduct formation (RAF) mechanisms. The rate constants of the chemical reaction were calculated using the conventional transition state theory (TST) and Eckart method (ZCT_0). The research is based on a QM-ORSA (Quantum Mechanics–based test for Overall free-Radical Scavenging Activity) protocol. For this purpose, the Gaussian 09 software package with the M06-2X/6-311++G(d,p) theoretical model was used. It has been shown that both compounds in benzene can inactivate the HO• radical via HAT and RAF mechanisms. The calculated kinetic parameters indicate that the TST method, in some positions, is not suitable for calculating reaction rate constants at room temperature. Based on relative antioxidant capacity (rT), both compounds showed better antioxidant capacity than Tx, and it should be emphasized that BER showed better activity than XAN. Based on the relative amount of products (Гi) of both compounds, it was concluded that the formation of a radical adduct in positions C-3, C-5, C-8, and C-2' is the most represented.

In the present paper, M05-2X/6-311+G(d,p) level of theory was used to investigate antiradical activity of cyanidin towards highly damaging radical species (.OH, .OCH3, .OOH and .OOCH3). The applied method successfully reproduces the values of reaction enthalpies (ΔHBDE, ΔHIP, and ΔHPA). These parameters are important to determine which of the mechanisms are preferred. Reaction enthalpies related to the antioxidant mechanisms of the investigated species were calculated in water and DMSO. The enthalpies of reactions indicate the preferred radical scavenging mechanisms in polar (water) and polar aprotic (DMSO) solvents. Single- electron transfer followed by proton transfer (SET-PT) is not a favorable reaction pathway under any conditions. Both remaining mechanisms, HAT and SPLET, are suitable for the reaction of cyanidin with •OH and •OCH3 in all solvents under investigation. On the other hand, in the reaction of cyanidin with •OOH and •OOCH3, the SPLET mechanism is possible in both solvents. Simulation of the reaction of the cyanidin anion with the hydroxy radical confirmed that position 3` of Cy‒O- is the most suitable for reaction with •OH through electron transfer mechanism (ET) in both solvents.

Coronavirus outbreak has influenced the global economy and everyday life of millions of people. The quest for the vaccine has already started but the limitations in productions and trial period made scientists look for alternatives, especially among naturally occurring molecules with proven biological significance. In this contribution, three recently synthesized coumarin derivatives with dopamine, norepinephrine, and octopamine were subjected to the molecular docking study and inhibitory activity determination towards SARS-CoV-2 main protease. All of the investigated molecules possess the rigid part which consists of fused heterocyclic/aromatic rings and a flexible part with electronegative atoms, therefore the study aims to provide answers about the importance of these moieties for the inhibitory activity. The results showed that coumarin derivatives with neurotransmitters have the binding energies between-39.83 and-46.26 kJ mol-1, as opposed to cinanserin (-43.56 kcal mol-1) and remdesivir (-60.08 kcal mol-1). The special emphasis in the discussion was put on the possibility of hydrogen bond formation, overall flexibility of molecules, and the position of OH groups. Based on the Fukui functions, the most active positions for electrophilic attack include aromatic OH groups of neurotransmitters and the carbonyl oxygen of coumarin. The probable nucleophilic and radical attack positions are carbon atoms of the rigid part with extended delocalization and carbonyl oxygen. The aliphatic OH groups lowered the flexibility and led to a decrease in the binding energy. Because all three derivatives passed the Lipinski rule of five, it is believed that further theoretical and experimental studies should be undertaken.

The article presents results obtained from molecular docking and molecular dynamic simulations to examine the inhibitory capacity of Entresto.