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Due to the well‐known biological potential of benzenesulfonamides for the inhibition of specific enzymes, here in, we propose to investigate anticholinesterase efficiencies of five newly synthesized benzenesulfonamides incorporating dimethoxyindole tails. The targeted compounds were synthesized through the C7 position of the methyl 4,6‐dimethoxy‐1H‐indole‐2‐carboxylate via Schiff‐base reaction. The biological study was directed to identify the acetylcholinesterase (ACh) and butyrylcholinesterase (BCh) enzyme inhibitions. The molecular docking studies were also carried out to determine the possible poses of ligands 8 a–e in binding sites of enzymes and ligand‐residue interactions. Molecular dynamics simulations, RMSD and RMSF plots, hydrogen bond analysis, per‐residue energy decomposition and MM‐PB(GB)/SA calculations were carried out investigate the potentials of the compounds towards the designated enzymes. It is important to note that all the synthesized compounds were found to be selective towards the BChE inhibition with a range of efficiencies. In addition to that the compound 8 a exhibited more potency than the standard Galanthamine with the value of 87.75 % for the same enzyme. The results could be valuable for the determination of new targets which are highly selective for BChE inhibition. The formation of hydrogen bonds and hydrophobic interactions with the residues located on the compounds were responsible for the binding free energy scores. The stability of all the compounds proved by molecular dynamics simulations were also promising for the further directions of the study. [ABSTRACT FROM AUTHOR]

Chemically and biologically important -C = N-N = C- diimine linkage was used to build unsymmetrical azine systems with indole heterocyclic backbone and substituted aromatic carbaldehydes. Ten novel compounds 7a-j were synthesized by the Schiff base reaction of 4,6-dimethoxyindole-7-hydrazone 5 and a range of substituted carbaldehydes 6a-j with high yields and purities. The biological study was directed to identify the antioxidant potentials due to the expected electronic delocalization capability of designated linkage which is important for possible hydrogen or electron donation. The three different assays, namely DPPH free radical scavenging, ABTS cationic radical decolarization and CUPRAC (cupric reducing antioxidant capacity) were employed to detect the antioxidant properties. The antioxidant potentials were found to be moderate for ABTS and CUPRAC assays and the compound 7j was the most potent candidate for all the antioxidant assays. More importantly, the anticholinesterase properties were investigated by acetylcholinesterase (ACh) and butyrylcholinesterase (BCh) enzyme inhibition assays. The molecular docking studies were also carried out to determine the possible poses of ligands 7a-j in binding sites of enzymes and ligand-residue interactions. The synthesized compounds were found to be more effective for the anticholinesterase activity with three promising candidates 7d, 7h and 7j in the case of BChE inhibitions. The compound 7h was determined as the best candidate with the comparable IC50 values for AChE and better inhibition potency for BChE with 7j. A range of hydrophobic and hydrophilic interactions were detected for the designated compound 7h and 7j through different amino acid residues and the computational results were found to be compatible with the biological counterparts. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome SARS‐CoV‐2 is the causative agent of COVID‐19. Preventing binding of SARS‐CoV‐2 Spike glycoprotein to human ACE2 enzyme and inhibition of MPRO enzyme are still attractive drug targets for treatment of COVID‐19 infection. Boron atom‐containing compounds show anticancer, antibacterial, antiviral, antifungal, antiparasitic, anti‐inflammatory, antituberculosis, anti‐dermatophytic and anti‐fertility activities. In the current study, the ADMET properties of ligands were calculated by the aim of SwissADME and pkCSM pharmacokinetics web tools. The results revealed that the ligands meet drug‐likeness properties. Furthermore, we have performed molecular docking study of boron containing dioxaborepine and oxadiazaborole derivatives to investigate binding properties of ligands against SARS‐CoV‐2 Spike glycoprotein/ACE2 complex and inhibition of MPRO enzyme. Through the ligands a derivative of dioxaborepine showed best binding score against SARS‐CoV‐2 Spike glycoprotein/ACE2 complex with a binding score of −8.93 kcal/mol and a oxadiazaborole derivative exhibited a binding score value of −8.36 kcal which is the best binding ligand to the MPRO enzyme binding site. The analysis of binding poses of ligands and ligand‐residue interactions of the systems revealed that dioxaborepines and oxadiazaboroles could have block binding of Spike glycoprotein to human ACE2 enzyme and could have inhibition effects on MPRO enzyme. [ABSTRACT FROM AUTHOR]

Designing new inhibitors having less side effects is a need which also could reduce cholesterol levels. To fulfill this aim, we have carried out a molecular docking study toward 3‐hydroxy‐3‐methyl‐glutaryl‐CoA (HMG‐CoA) reductase. A set of designed structural derivatives of statin drugs, eight ligands which are used as HIV‐1 integrase inhibitor candidates, a set of terpenoids, and ligands downloaded from Zinc15 database were docked to HMG‐CoA reductase enzyme which contains atorvastatin in crystal structure. The analysis of docking studies revealed that statin derivative ligands are more appropriate for inhibition of HMG‐CoA reductase. To define the contribution of the molecular properties to the binding of ligands to enzyme structure; the highest occupied molecular orbitals‐lowest unoccupied molecular orbitals, hardness, electronegativity, and chemical potential properties of ligands have best score in their sets calculated by quantum mechanical tools. [ABSTRACT FROM AUTHOR]

This work involves a facile synthesis of three (S)-proline-based organocatalysts with C2 symmetry and their effects in enantioselective aldol reaction of acetone with substituted aromatic aldehydes. Moderate enantioselectivities (up to 61% ee) were obtained depending on the nature of the substituents on the aryl ring. Computational calculations at HF/6-31 + G(d) level were employed to underline the enantioselectivity imposed by all the organocatalysts. Higher calculations at B3LYP/6-311 ++ G(d,p) scrf=(solvent=dichloromethane)//B3LYP/6-31 + G(d) levels of theory were also performed for the aldol reaction of acetone with benzaldehyde and 4-nitrobenzaldehyde catalyzed by 1. The computational outcomes were consistent with those produced by experimental results and they were valuable to elucidate the mechanism for the observed stereoselectivity. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV), a member of human herpesvirus, causes infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, gastric carcinoma and Hodgkin lymphomas. Epstein-Barr Nuclear Antigen 1, one of antigens encoded by EBV, comprises 641 amino acid residues. Among the latent infection Epstein-Barr Nuclear Antigen 1 acts in DNA replication, transcription of viral and cellular genes and in immortalisation of B lymphocytes. These special roles of Epstein-Barr Nuclear Antigen 1 make it an important drug target. Therefore, in this study, we create a ligand set of totally 2068 ligands to block binding DNA to Epstein-Barr Nuclear Antigen 1 antigen. After applying Lipinski's Rule of Five filter to these ligands, 1637 ligands which are suitable to be a drug were run into molecular docking studies. It was seen that designed ligands show more activity to prevent binding DNA to Epstein-Barr Nuclear Antigen 1 antigen rather than ligands selected from the literature which are also studied in vitro and in silico. [ABSTRACT FROM AUTHOR]

This study consists of two parts. In the first part of the study; a Pirkle-type chiral stationary phase was prepared by synthesizing an aromatic amine derivative of (R)-2-amino-1-butanol as a chiral selector and binding to L-tyrosine-modified cyanogen bromide (CNBr)-activated Sepharose 4B and then, packed into the separation column. The chromatographic performance of the separation column was evaluated with racemic mandelic acid and 2-phenylpropionic acid by using phosphate buffers at three different pHs as mobile phase. In the resolution processes, the prepared solutions were loaded onto the separation column at two different concentrations and at three different pHs for each racemic organic acid, separately. Enantiomeric excess (ee%) of the eluates was determined on CHIRALPAK AD-H chiral analytical column by HPLC. The maximum ee% for mandelic acid and 2-phenylpropionic acid was determined to be 60.84 and 27.4, respectively. Separation factors (k1', k2', α, and Rs) were calculated for each acid. The structures of the obtained compounds were characterized using the spectroscopic methods (NMR, and elemental analysis). In the second part of the study; enantioselective interactions between the prepared CSP and the analytes have been widely studied by docking, molecular dynamics simulation and quantum mechanical computation methods. The reason of column eluation of rac-2-phenylpropionic acid with lower enantiomeric yield was explained by these techniques. [ABSTRACT FROM AUTHOR]

Let {ϑn}n=1∞ be a sequence of words. If there exists a positive integer n such that ϑm{G) = 1 for every m ≥ n, then we say that G satisfies (*) and denote the class of all groups satisfying (*) by ... {ϑn}n=1∞. If for every proper subgroup K of G, K ∈...{ϑn}n=1∞ but G ...{ϑn}n=1∞, then we call G a minimal non-...{ϑn}n=1∞-group. Assume that G is an infinite locally finite group with trivial center and ϑi(G) = G for all i ≥ 1. In this case we mainly prove that there exists a positive integer t such that for every proper normal subgroup N of G, either ϑt(N) = 1 or ϑt(CG(N)) = 1. We also give certain useful applications of the main result. [ABSTRACT FROM AUTHOR]

The bimolecular rate constants for the globin- and alkali-catalysed hydrolysis of substituted phenyl hexanoates in the absence and presence of cetyltrimethylammonium bromide (CTAB) obey Brønsted equations with β = −0.53 (globin-catalysed), −0.68 (globin-catalysed in CTAB), −0.34 (in water) and −0.74 (in CTAB), respectively. The slopes indicate that the microsolvation environments associated with the transition states of the catalysed reactions are different from those that occur in aqueous medium. The slope (−0.74) for the reaction in CTAB implies that it proceeds in a less polar medium. The larger β value (−0.53) obtained for the globin-catalysed reaction compared to that for the uncatalysed one may be attributed to either the less polar microenvironments of the transition states or the involvement of one of the imidazole groups as a nucleophile. The results from a study of the effect of pH on the reactivity provide evidence for the latter assumption. All of the ligands were docked into the hydrophobic pocket of the protein, and the resulting docking scores ranged from −30.76 to −23.61 kcal mol. Molecular dynamic simulations and MM-PBSA/GBSA calculations performed for the complexes gave insight into the binding modes of globin to the esters, which are consistent with experimental results. The calculations yielded comparable free energies of binding to the experimental ones for 4-nitrophenyl and 4-chloro-2-nitrophenyl hexanoates. In conclusion, information obtained from the linear free-energy relationship is still very useful for elucidating the mechanisms of organic reactions, including enzyme-catalysed reactions. This approach is further supported by the utilization of computational tools. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A full-length model of integrase (IN) of the human immunodeficiency virus type 1 (HIV-1) was constructed based on the distinctly resolved X-ray crystal structures of its three domains, named N-terminal, catalytic core and C-terminal. Thirty-one already known inhibitors with varieties of structural differences as well as nine newly tested ones were docked into the catalytic core. The molecular dynamic (MD) and binding properties of these complexes were obtained by MD calculations. The binding energies calculated by molecular mechanic/Poisson Boltzmann solvation area were significantly correlationed with available IC. Four inhibitors including two newly designed were also docked into the full-length model and their MD behaviors and binding properties were calculated. It was found that one of the newly designed compounds forms a better complex with HIV-1 IN compared to the rest including raltegravir. MD calculations were performed with AMBER suite of programs using ff99SB force field for the proteins and the general Amber force field for the ligands. In conclusion, the results have produced a promising standpoint not only in the construction of the full-length model but also in development of new drugs against it. However, the role of multimer formation and the involvement of DNAs, and their subsequent effect on the complexation and inhibition, are required to arrive at a conclusive decision. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We consider groups whose all infinite subgroups have a bound on subnormal indices and prove that these groups are soluble or nilpotent with some additional conditions. [ABSTRACT FROM AUTHOR]

Presents a study that discussed groups, all proper subgroups of which are hypercentral of length and every subgroup of which is a group for a natural number depending on the subgroup. Overview of a locally graded torsion-free group and subgroup; Option for a group to be a hypercentral group; Groups as a locally nilpotent group.

• A cocrystal of 5-fluorouracil (5-FU) with 2,2'-dipyridylamine (dpya) was prepared. • The cocrystal had a 3D-network formed via hydrogen bonds and π-π interactions. • The cocrystal displayed increased thermal stability compared to dpya. • Anticancer potential of the cocrystal was investigated through molecular docking. • The cocrystal showed stronger thymidylate synthase inhibition than 5-FU and FdUMP. A new cocrystal containing 5-fluorouracil (5-FU) and 2,2'-dipyridylamine (dpya) was successfully prepared by a slow evaporation solution method and characterized using solid-state techniques such as FTIR, thermal analysis (DTA/TG) and single crystal X-ray diffraction. X-ray crystallography indicated the formation of a 2:1 5-FU:dpya cocrystal. The 5-FU and dpya molecules in the cocrystal were linked by N−H···O, N−H···N, C−H···O and C−H···F hydrogen bonds, forming a two-dimensional layers, further extended to a three dimensional supramolecular network via π-stacking interactions. Thermal analysis data showed that the cocrystal exhibited a lower thermal stability than 5-FU, but it is more stable than dpya. Molecular docking method was used to investigate in silico anticancer activity of the new co-crystal against a cancer target protein, human thymidylate synthase (TS). The free binding affinity of the cocrystal towards TS was notably higher than those of both reference ligands 5-FU and 5-fluorodeoxyuridine monophosphate (FdUMP), indicating the enzyme inhibition and anticancer potential of the cocrystal. Additionally, the molecular dynamics (MD) simulation and binding free energy studies confirmed the stability of the TS-cocrystal complex in a period of 50 ns. [Display omitted] [ABSTRACT FROM AUTHOR]

• This is the first study that comprehensively reveals anti-Alzheimer and anti-multiple sclerosis activities of the synthesized oxime compounds through in silico and in vitro perspectives. • Molecule 4 extraordinarily showed outstanding activity against Alzheimer's disease both in silico and in vitro , as well as in silico activity against multiple sclerosis. This feature makes molecule 4 a possible drug lead molecule which is very limited in the market. • Correlations are obtained between anti-Alzheimer and anti-MS effects, as well as between in silico and in vitro results, which is very precious. Alzheimer disease (AD) and multiple sclerosis (MS) are inflammatory neurological disorders. The main symptom of AD is dementia, and the main symptoms of MS are vertigo, sexual dysfunction, cognitive problems, and fatigue. Today, millions of people are affected by AD and MS, and the number is growing day by day. However, there are not any accurate remedies for both disorders. For this reason, discovering novel drug molecules against neurological disorders such as AD and MS is essential and precious. Oximes and benzofurans exhibit many pharmacological effects including anti-inflammatory and neurological activities. Thus, several novel compounds bearing oxime and benzofuran chemical cores were designed and synthesized, and their in vitro anticholinesterase activities were investigated in our previous study. A number of the synthesized molecules showed excellent anticholinesterase activity against both AChE and BChE enzymes. The mentioned study constituted a background for this study. In this study, we picked different chemical skeletons among all the synthesized molecules to conduct further in silico and in vitro experiments. In order to support our in vitro anticholinesterase findings, we also examined in silico anti-Alzheimer activity of the selected molecules. In addition, in silico and in vitro activities against MS disease of the synthesized molecules were investigated. Molecule 4 extraordinarily showed outstanding activity against AD disease both in silico and in vitro , as well as in silico activity against MS disease. This feature makes molecule 4 a possible drug lead molecule which is very limited in the market. On the other hand, molecule 1 , a less substituted oxime skeleton, demonstrated the strongest in vitro activity against MS disease through in vitro anti-inflammatory effect. As an observation, molecule 4 was determined to be the most promising molecule to focus on in the further steps. [Display omitted] [ABSTRACT FROM AUTHOR]

In this paper, we consider locally nilpotent minimal non-soluble groups. It is proved that if G is a locally nilpotent group with all proper subgroups soluble and for every element x of G, < x >G of finite exponent then, G is soluble. Furthermore, G is Baer group. [ABSTRACT FROM AUTHOR]

Biologically important hydrazide-hydrazone (–(C=O)NHN=CH) functionality was located at two different positions on 4,6-dimethoxyindole moiety and novel compounds 11a-c and 12a-c were generated by the condensation reactions of indole hydrazones 7 and 8 , derived from the corresponding indole carbaldehydes 4 and 6 , and carboxylic acids 9a-c in the presence of amide coupling reagent (EDC). The anticholinesterase potency was investigated towards the acetyl- and butrylcholinesterase enzymes (AChE and BChE) and complementary determination of biological potency was obtained by the evaluation of binding scores. The compound 11b resulted the best binding behaviors due to the hydrophobic interactions with the responsible amino acids on the different active sites of enzymes pocket. The structural analysis revealed that the most favorable binding pose was mainly dependent on the presence of aromatic moiety administered by the benzoic acid as well as the hydrazide-hydrazone linker but not related with the location on indole ring. Most importantly, the biological study was found to be compatible with the molecular modeling study and the highest inhibition was determined in the presence of compound 11b with the values of 83.31 and 73.55 for AChE and BChE, respectively. • The concise and high yielded synthesis of novel hydrazide-hydrazone derivatives located on different positions on 4,6-dimethoxyindole systems are achieved by the amide coupling reactions. • The presence of indole heterocyclic ring with the hydrazide-hydrazone moiety create new potent anticholinesterase inhibitors. • Molecular docking studies reveal the structural insights of novel hydrazide-hydrazones by the interactions on the anticholinesterase enzymes. [ABSTRACT FROM AUTHOR]

Since ancient times, Teucrium L. species have been among the most commonly used traditional medicinal plants mainly in the Mediterranean region. From tackling gastrointestinal problems to maintaining the healthy functioning of endocrine glands, and from treating malaria to severe dermatological disorders, Teucrium species are known to have extensive therapeutic applications. Teucrium polium L. and Teucrium parviflorum Schreb. are the two members of the genus that have been used in Turkish folk medicine for various medicinal purposes. To determine the phytochemical compositions of the essential oils and ethanol extracts of Teucrium polium and Teucrium parviflorum collected from different locations in Turkiye along with the investigation of in vitro antioxidant, anticancer, antimicrobial activities, and both in vitro and in silico enzyme inhibitory activities of the extracts. Ethanol extracts of Teucrium polium aerial parts and roots, and aerial parts of Teucrium parviflorum were prepared. Volatile profiling of the essential oils by GC-MS, phytochemical profiling of the ethanol extracts by LC-HRMS, antioxidant activity by DPPH radical scavenging, ABTS cation radical scavenging, CUPRAC, and metal chelating activity assays, anticholinesterase, antityrosinase, antiurease, activities by different enzyme inhibitory activity assays, anticancer activity by SRB cell viability assay, and antimicrobial activity against a standard panel of bacteria and fungi by the microbroth dilution technique. Molecular docking studies were performed by Autodock Vina (Ver. 1.1.2). The studied extracts were found to be quite rich in various biologically important volatile and phenolic compounds. (−)-Epigallocatechin gallate, which is a molecule renowned for having great therapeutic potential, was the major compound of all extracts. Teucrium polium aerial parts extract was revealed as a great source for naringenin with 16327 ± 685.23 μg/g extract. All extracts exerted significant antioxidant activity by different methods. All extracts demonstrated antibutrylcholinesterase, antityrosinase, and antiurease activities by in vitro and in silico assays. Teucrium polium roots extract stood out with remarkable tyrosinase and urease inhibitory and cytotoxic activities. The obtained results from this multi-disciplinary study proves that the traditional use of these two Teucrium species is justified, and the mechanisms behind are enlightened. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, some thermodynamic properties of poly(2‐[3‐(6‐tetralino)‐3‐methyl‐1‐cyclobutyl]‐2‐hydroxy ethyl methacrylate) P (TMCBHEMA) and poly[2‐(3‐mesityl‐3‐methyl‐1‐cyclobutyl)‐2‐oxoethyl methacrylate) P (MCBOEMA) such as the adsorption enthalpy, ΔHa, molar evaporation enthalpy, ΔHv, the sorption enthalpy, ΔH1s, sorption free energy, ΔG1s, sorption entropy, ΔS1s, the partial molar free energy, ΔG1∞, the partial molar heat of mixing, ΔH&strns;1∞, at infinite dilution were determined for the interactions of PTMCBHEMA and PMCBOEMA with selected alcohols and alkanes by the inverse gas chromatography (IGC) method in the temperature range of 333–463 K. According to the specific retention volumes, Vg0, the weight fraction activity coefficients of solute probes at infinite dilution, Ω1∞, and Flory‐Huggins interaction parameters, χ∞12 between PTMCBHEMA and PMCBOEMA‐solvents were determined in 433–463K and 443–463K, respectively. According to Ω1∞ and χ∞12, selected alcohols and alkanes were found to be non‐solvent for PTMCBHEMA at 433–463 K, but the same solvents (except for decane) were found to be solvent for PMCBOEMA at 443–463K. The glass transition temperature, Tg, of the PTMCBHEMA and PMCBOEMA found to be 380 and 383; 390 K and 388 K, by IGC and DSC techniques, respectively. [ABSTRACT FROM AUTHOR]

Two novel amide-based receptors were synthesized under microwave irradiation. Their chemical structures were confirmed by IR, H NMR, C NMR, and elemental analysis. The binding properties of these amide-based receptors to various anions (HPO , HSO , CHCO , CHCO , ClO , F, Cl, and Br) were examined by UV titration in THF at 20 °C. The results indicated that the receptors form 1:1 complexes with anions and they have the strongest affinity for fluoride (F) among the anions considered. Molecular dynamics calculations by AMBER and quantum mechanical calculations performed at the B3LYP and M062X levels of theory using the 6-31 + g(d,p) basis set provided models for the complexation mode between the receptors and anions and yielded binding energies for the complexes. [ABSTRACT FROM AUTHOR]

This study, reports the synthesis and characterization of two new copolymers (poly[2-(pchlorophenyl)- 1,3-dioxolane-4-yl] methyl acrylate-co-styrene (PCPhDMA-co-St) and poly[2-(pchlorophenyl)- 1,3-dioxolane-4-yl] methyl acrylate-co-acrylonitrile (PCPhDMA-co-AN)). Copolymers were characterized by spectral (FT-IR, ¹H - NMR) and thermal analysis (TGA, DSC). Their thermodynamic properties, such as the adsorption enthalpy, ΔHa, molar evaporation enthalpy, ΔHv, the sorption enthalpy, ΔH¹ s, sorption free energy, ΔG1 s, sorption entropy, ΔS1 s, the partial molar free energy, ΔG1 ∞, the partial molar heat of mixing, ΔH1 ∞, at infinite dilution were studied by inverse gas chromatography. Depending on specific retention volumes, Vg 0, of probes the weight activity coefficients of solute probes at infinite dilution, Ω1 ∞, and Flory-Huggins interaction parameters, between PCPhDMA-co-St and PCPhDMA-co-AN-solvents were investigated in the range of 413-453 K and 403-453 K, respectively. [ABSTRACT FROM AUTHOR]

This study, reports the synthesis and characterization of two new copolymers (poly[2-(p-chlorophenyl)-1,3-dioxolane-4-yl] methyl acrylate-co-styrene (PCPhDMA-co-St) and poly[2-(p-chlorophenyl)-1,3-dioxolane-4-yl] methyl acrylate-co-acrylonitrile (PCPhDMA-co-AN)). Copolymers were characterized by spectral (FT-IR, ¹H - NMR) and thermal analysis (TGA, DSC). Their thermodynamic properties, such as the adsorption enthalpy, ΔHa, molar evaporation enthalpy, ΔAHv the sorption enthalpy, ΔH1s, sorption free energy, ΔG1s, sorption entropy, ΔS1s, the partial molar free energy, ΔG1∫, the partial molar heat of mixing, ΔH1∫, at infinite dilution were studied by inverse gas chromatography. Depending on specific retention volumes, Vg0, of probes the weight activity coefficients of solute probes at infinite dilution, Ω1∫, and Flory-Huggins interaction parameters, χ12∫ , between PCPhDMA-co-St and PCPhDMA-co-AN-solvents were investigated in the range of 413-453 K and 403-453 K, respectively. [ABSTRACT FROM AUTHOR]