Ternary Transition Metal Complexes with an Azo-Imine Ligand and 2,2’-Bipyridine: Characterization, Computational Calculations, and Acetylcholinesterase Inhibition Activities

New mononuclear ternary transition metal complexes: [M(HL)(bipy)2]ClO4, (M: Mn(II) for 1, Ni(II) for 2), [M(HL)(bipy) (ClO4)], (M: Ni(II) for 3, Cu(II) for 4, Zn(II) for 5) with M(II), 2-[(E)-(hydroxyimino)methyl]-4-[(E)-phenyldiazenyl]phenol, H2L, and 2,2ˈ-bipyridine were synthesized. The structures of the complexes were investigated by using various analytical, spectroscopic techniques such as elemental analysis, FTIR, UV-Vis, NMR, MALDI-TOF mass spectrometry, thermal analysis, and computational studies containing geometric optimizations and theoretical calculations of vibrations and electronic transitions. IR and thermal analysis data verifies the proposed structure of the complexes. The inhibition activities of the complexes against acetylcholinesterase (AChE) extracted from Ricania simulans adults and nymphs were examined and all the complexes were found to be active. Among the complexes studied, the most inhibition activity was exhibited by complex 5 with the lowest IC50 value (3.2±0.8) for AChE of adults, complex 3 with the lowest IC50 value (4.6±0.8) for AChE of nymphs

Artemisinin türevi bileşiklerin sars-cov-2 ana proteaz proteinine karşı in silico inhibisyon potansiyeli

The outbreak of COVID-19 caused by the SARS-CoV-2 virus has recently affected millions worldwide. The natural compounds obtained from medicinal plants have been proven to be the source of many treatments throughout history. Efforts to combat Sars-CoV-2 generally focused on repositioning drugs or finding treatments with natural compounds and have been rapidly ongoing. Main protease (Mpro) is a vital protein of SARS-CoV-2 and an important target of drug research. The present study evaluated seven artemisinin derivatives: artemisinin, artemether, arteether, artesunate, dihydroartemisinic acid, dihydroartemisinin and artemisinic acid. For this purpose, the molecular docking study was carried out to investigate the potency of artemisinin derivatives against the SARS-CoV-2 Mpro. As a result, artesunate, dihydroartemisinic acid and dihydroartemisinin had promising results in Mpro inhibition with the binding energies between-8.42 and-9.35 kcal/mol

Potential therapeutic effect of turmeric contents against SARS-CoV-2 compared with experimental COVID-19 therapies: in silico study

emirik, mustafa/0000-0001-9489-9093WOS: 000579707000001PubMed: 33078675Inspired by the 'There is no scientific evidence that turmeric prevents COVID-19' statement made by WHO, the protective or therapeutic potential of the compounds in turmeric contents was investigated against COVID-19 with in silico methodology. the drugs used for experimental COVID-19 therapies were included in this study using the same method for comparison with turmeric components. the 30 turmeric compounds and nine drugs were performed in the docking procedure for vital proteins of COVID-19. With evaluations based on docking scores, the Prime MMGBSA binding free energy and protein-ligand interactions were identified in detail. the 100 ns MD simulations were also performed to assess the stability of the ligands at the binding site of the target proteins. the Root Mean Square Deviation (RMSD) is used to obtain the average displacement for a particular frame concerning a reference frame. the results of this study are suggesting that turmeric spice have a potential to inhibit the SARS-CoV-2 vital proteins and can be use a therapeutic or protective agent against SARS-CoV-2 via inhibiting key protein of the SARS-CoV-2 virus. the compound 4, 23 and 6 are the most prominent inhibitor for the main protease, the spike glycoprotein and RNA polymerase of virus, respectively. the MD simulation validated the stability of ligand-protein interactions. the compactness of the complexes was shown using a radius of gyration. ADME properties of featured compounds are in range of 95% drug molecules. It is hoped that the outputs of this study will contribute to the struggle of humanity with COVID-19

Comparison of electrostatic potential obtained from different atomic point charges calculation methods for a large set of molecules

The Electrostatic Potential is of great importance in chemical reactivity since it is closely related to many of molecular properties. Despite the fact that there are significant improvements in the quantum mechanical calculation methods, the atom centered partial charge approximation keeps hold of its importance in the field of estimating electrostatic potential as an inexpensive alternative to the ab initio method. However, even today, there is no universally accepted the best method for computing a partial atomic charge. Here, we compared the electrostatic potential obtained from different atomic point charges calculation methods for a large set of molecules. To this end, the large Grimme set of molecules was used. Some of the molecules in the set naturally failed in estimating the electrostatic potential. This failure, therefore, was investigated in depth. The Iterative Hirshfeld method can be preferable for electrostatic potential field generation

Synthesis, alpha-glucosidase inhibition and in silico studies of some 4-(5-fluoro-2-substituted-1H-benzimidazol-6-yl)morpholine derivatives

emirik, mustafa/0000-0001-9489-9093WOS: 000552631700004PubMed: 32563964In this study, a new series of 4-(5-fluoro-2-substituted-1H-benzimidazol-6-yl)morpholine derivatives has been synthesized and screened for their alpha-glucosidase inhibitory potential. All molecules showed a considerable alpha-glucosidase inhibitory potential with IC50 values ranging from 20.46 +/- 0.21 to 0.18 +/- 0.01 mu g/mL when compared with the acarbose (IC50 = 8.16 +/- 0.12 mu g/mL) as the standard. Compound 4 k having methoxy group on phenyl ring had the highest inhibitory effect with IC50 = 0.18 +/- 0.01 mu g/mL value among the examined compounds. Electron-donating groups such as methyl and methoxy on the phenyl ring played an important role in the inhibition. Also, the Lineweaver-Burk plots analysis displayed that the inhibition type of 4k was the competitive mode like acarbose as standard. in silico studies were also performed to explore the binding interaction of the most active compound

Synthesis and Molecular Docking Studies of Novel Triazole Derivatives as Antioxidant Agents

emirik, mustafa/0000-0001-9489-9093WOS: 000522111400010A series of 1,2,4-triazole and 1,2,4- thiadiazole derivatives were prepared starting from ethyl 4-(3-methyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)benzoate. Firstly, both ethyl ester groups were simultaneously transformed into hydrazide groups, then into thiosemicarbazide groups using both microwave-assisted and conventional methods. the latter products were interacted with NaOH and H2SO4 to form ring assemblies containing two 1,2,4-triazole and 1,3,4-thiadiazole fragments, respectively. Antioxidant activities of the synthesized compounds were determined with CUPRAC, ABTS, and DPPH assays. Most of the compounds showed significant antioxidant activity and especially, compound 3 exhibited very good SC50 value for DPPH method and compound 3, 4a, 5a exhibited very high scavenging activity to the ABTS method. in addition, the in silico analysis was carried out with the synthesized derivatives to understand the mode of interaction with superoxide dismutase (SOD) and human tyrosine kinase using docking protocols in order to find out the most active antioxidant drug having high inhibitory activity in cancer.Scientific and Technical Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T640]The authors gratefully acknowledge the financial support from the Scientific and Technical Research Council of Turkey (TUBITAK) through Project 112T640

Design, molecular docking and synthesis of novel 5,6-dichloro-2-methyl-1H-benzimidazole derivatives as potential urease enzyme inhibitors

WOS: 000464108100016PubMed: 30710848A novel series of 5,6-dichloro-2-methyl-1H-benzimidazole derivatives was synthesized and then screened for their urease inhibitory activity. All compounds showed more potent inhibitory activity in the range of IC50= 0.0294 +/- 0.0015-0.1494 +/- 0.0041 mu M than thiourea (IC50= 0.5117 +/- 0.0159 mu M), as a reference inhibitor. Among all the tested compounds, the compound 15 (IC50= 0.0294 +/- 0.0015 mu M) having strong electron-withdrawing nitro group on the phenyl ring was recorded as the most potent inhibitor of urease. All compounds were docked at the active sites of the Jack bean urease enzyme to investigate the reason of the inhibitory activity and the possible binding interactions of enzyme-ligand complexes

Synthesis and molecular docking studies of potent urease inhibitors based on benzoxazole scaffold

In this study, we report the synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzoxazole derivatives. The title compound in the series namely (2-(benzo[d]oxazol-2-ylthio)-1-(4-substitute-phenyl)ethan-1-one oxime was synthesized by the reaction of 2-aminophenol with different kinds of intermediates in several steps through both conventional and microwave techniques. All compounds were found to have an excellent degree of urease inhibitory potential ranging from 0.46 +/- 0.01 to 46.10 +/- 0.45 mu M in compared with standard inhibitor acetohydroxamic acid with IC50 320.70 +/- 4.24 mu M. Structure-activity relationship was established in detail. In addition, we confirmed the binding interactions of compounds with enzymes using molecular docking

Synthesis and characterization of two new hydroxamic acids derivatives and their metal complexes. An investigation on the keto/enol, E/Z and hydroxamate/hydroxirnate forms

Ozil, Musa/0000-0002-1980-1364; YILMAZ, Fatih/0000-0002-7711-0975; emirik, mustafa/0000-0001-9489-9093WOS: 0003859018000482-phenylbenzimidazole-N-acetohydroxamic acid (HL1), 2-phenylbenzimidazole-N-butanohydroxamic acid (HL2) and Ni(II), Cu(II), Zn(II) and Cd(II) metal complexes have been synthesized and characterized by elemental analyses, H-1 NMR, C-13 NMR, FT-IR spectrometry, LC-MS (ESI+) and thermal analyses. the results of NMR spectra and theoretical calculations showed that the hydroxamic acids were in the keto-E and keto-Z conformations. the elemental analysis and thermal analysis indicated that M:L ratio of the complexes are 1:1 and the spectral analysis confirmed that hydroxamate groups are keto form in the Ni(II) and Zn(II) complexes of 2-phenylbenzimidazole-N-butanohydroxamic acid and enol form in the other complexes. (C) 2016 Elsevier B.V. All rights reserved.Research Fund of the Recep Tayyip Erdogan University [BAP-2013.102.02.4]This work was supported by Research Fund of the Recep Tayyip Erdogan University, Project Number: BAP-2013.102.02.4. the theoretical calculations reported in this paper were fully performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources)

Synthesis and molecular docking study of some novel 2,3-disubstituted quinazolin-4(3H)-one derivatives as potent inhibitors of urease

emirik, mustafa/0000-0001-9489-9093WOS: 000441537800014PubMed: 29894891A new series of 2,3-disubstituted quinazolin-4(3H)-one compounds including oxadiazole and furan rings was synthesized. Their inhibitory activities on urease were assessed in vitro. All newly synthesized compounds exhibited potent urease inhibitory activity in the range of IC50 = 1.55 +/- 0.07-2.65 +/- 0.08 mu g/mL, when compared with the standard urease inhibitors such as thiourea (IC50 = 15.08 +/- 0.71 mu g/mL) and acetohydroxamic acid (IC50 = 21.05 +/- 0.96 mu g/mL). 2,3-Disubstituted quinazolin-4(3H)-one derivatives containing furan ring (3a-e) were found to be the most active inhibitors when compared with the compounds 2a-e bearing oxadiazole ring. Compound 3a, bearing 4-chloro group on phenyl ring, was found as the most effective inhibitor of urease with the IC50 value of 1.55 +/- 0.11 mu g/mL. the molecular docking studies of the newly synthesized compounds were performed to identify the probable binding modes in the active site of the Jack bean urease (JBU) enzymes