Molecular Docking and Dynamic Simulation Studies of Benzoylated Emodin into HBV Core Protein

Firdayani,; Arsianti, Ade; Churiyah,; Yanuar, Arry

doi:10.5530/jyp.2018.2s.5

Cited by 10 publications

(13 citation statements)

References 17 publications

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“…The title molecule (4) has been tested as a system which interacts with the capsid of HBV (Hepatitis-B virus). The main approach to anti-HBV agents’ development is associated with the search of potent inhibitors of HBV replication [32, 33, 34, 35]. Such ligands demonstrate effective interactions with corresponding HBV capsid and newly synthesized core protein.…”

Section: Resultsmentioning

confidence: 99%

“…We performed the study of the title molecule biological activity according to the experimental in vitro hepatitis B virus infection model with the usage of human hepatoma line HepG2 [34,35]. This model was designed in two manners in order to determine the precise stages of HBV infection development that is affected by the tested compound.…”

Section: Resultsmentioning

confidence: 99%

“…The cells were additionally incubated for 6 days at 37 °C in a humidified atmosphere containing 5% carbon dioxide. Next, cell supernatants (50 μL) were analyzed for viral antigen content using a commercial HBeAg ELISA 4.0 kit (Creative Diagnostics, catalog number DEIA003) according to the kit manufacturer's protocol and the optical density of each analyzed well was measured at a wavelength of 450 nm using a plate densitometer [35].…”

Section: Methodsmentioning

confidence: 99%

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Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate

Ivachtchenko¹,

Mitkin²,

Kravchenko

et al. 2019

Heliyon

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A method of 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate synthesis has been developed and the electronic and spatial structure of a new biologically active molecule has been studied both theoretically and experimentally. The title compound was crystallized from acetonitrile and the single crystal X-ray analysis has revealed that it exists in a monoclinic P21/c space group, with one molecule in the asymmetric part of the unit cell. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking study evaluates the investigated compound as a new potential inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance demonstrates in vitro nanomolar inhibitory activity against HBV.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate

Ivachtchenko¹,

Mitkin²,

Kravchenko

et al. 2019

Heliyon

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“…Among the prospective agents which strongly interact with corresponding key proteins are derivatives of heteroaryldihydropyrimidine (HAP) [28][29][30]. Investigations of HAP (among them the most important chemical compounds-BAY41-4109, BAY39-5493, NVR-010-001-E2 [31][32][33]) demonstrated effective interactions with the corresponding HBV capsid and newly synthesized core protein. After interaction, the core protein could not assembly properly.…”

Section: Molecular Docking Simulationsmentioning

confidence: 99%

Synthesis, X-Ray Crystal Structure, Hirshfeld Surface Analysis, and Molecular Docking Study of Novel Hepatitis B (HBV) Inhibitor: 8-Fluoro-5-(4-fluorobenzyl)-3-(2-methoxybenzyl)-3,5-dihydro-4H-pyrimido[5,4-b]indol-4-one

Иващенко¹,

Mitkin²,

Kravchenko

et al. 2019

Crystals

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A method for the synthesis of 8-fluoro-5-(4-fluorobenzyl)-3-(2-methoxybenzyl)-3,5-dihydro-4H-pyrimido [5,4-b]indol-4-one has been developed and the electronic and spatial structure of a new biologically active molecule has been studied both theoretically and experimentally. The title compound was crystallized from acetonitrile and the single-crystal X-ray analysis has revealed that it exists in a monoclinic P2 1 /n space group, with one molecule in the asymmetric part of the unit cell, a = 16.366(3) Å, b = 6.0295(14) Å, c = 21.358(4) Å, β = 105.21(2) • , V = 2033.7(7) Å 3 and Z = 4. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking studies have evaluated the investigated compound as a new inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance has in vitro nanomolar inhibitory activity against Hepatitis B virus (HBV). under investigation contain nitrogen heterocycles, and of these, 1H-indoles and pyrimidin-4(3H)-ones form a very substantial type of compounds. These heterocycles have the "privileged" indole framework which is commonly found in natural products and pharmaceutical drugs [7][8][9][10][11][12]. Pyrimidoindole moieties [13][14][15] are important structural motifs which are found in numerous pharmaceutically active compounds. They have revealed a wide range of high biological activity, such as antihypertensive and anti-inflammatory [16], anti-asthma [17,18], and act as α1-adrenergic receptor ligands or A1 adenosine receptor antagonists [19], potential tyrosine kinases (PTK) inhibitors, CFR1 and neuropeptide Y receptor ligands [20]. Despite the large spectrum of biological activity of these moieties, this range can be supplemented by introducing certain functional groups. Therefore, it is of substantial interest to develop efficient methods for the synthesis of such structures and their derivatives.In a continuation of our efforts to obtain new HBV inhibitors for treatment and prevention of human HBV infections [21,22], we initiated the design, synthesis, and anti-hepatitis B virus activity testing of a new 8-fluoro-5-(4-fluorobenzyl)-3-(2-methoxybenzyl)-3,5-dihydro-4H-pyrimido [5,4-b] indol-4-one. Single-crystal X-ray analysis and different spectroscopic techniques assured the assigned chemical structure of the title compound. In addition, molecular docking simulations and study were also executed for the title compound. Results and DiscussionIn frames of the development of a platform for biologically active compound libraries, design for actual biotargets, including platform testing on the example of the invention and preparation of candidate libraries for HBV treatment designed as inhibitors of viral penetration and assembly of viral core particles, we have carried out a pilot in vitro screening of a series of new compounds. At the first stage of the cytotoxicity pilot screening, all the potential inhibitors of viral infection were studied, of which about 1000 showed cytotoxicity over 50% at 10 µM. A...

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“…Nowadays, the main approach to creating anti-hepatitis B virus (HBV) agents is by developing a highly effective HBV replication depressor [13]. Heteroaryl dihydropyrimidines (HAP), such as BAY39-5493, BAY41-4109, NVR-010-001-E2 (Figure 1) are promising agents (HBV inhibitors) which have demonstrated interaction with the corresponding HBV core (HBcAg) proteins [14][15][16]. The PDB codes of HBV capsids are 5E0I, 5T2P, 5WRE and 5GMZ.…”

Section: Introductionmentioning

confidence: 99%

Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

et al. 2020

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Consecutive alkylation of 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by CH3I has been investigated to establish regioselectivity of the reaction for reliable design and synthesis of combinatorial libraries. In the first stage, the product of S-methylation-methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate was obtained. The subsequent alkylation with CH3I led to the formation of both O- and N-methylation products mixture-methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate and methyl 1-methyl-2-(methylthio)-4-oxo-1,4-dihydroquinoline-3-carboxylate with a predominance of O-methylated product. The structure of synthesized compounds was confirmed by means of elemental analysis, 1H-NMR, 13C-NMR, LC/MS, and single-crystal X-ray diffraction. The quantum chemical calculations of geometry and electron structure of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate’s anion were carried out. According to molecular docking simulations, the studied compounds can be considered as potent inhibitors of Hepatitis B Virus replication. Experimental in vitro biological studies confirmed that studied compounds demonstrated high inhibition of HBV replication in 10 µM concentration.

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Molecular Docking and Dynamic Simulation Studies of Benzoylated Emodin into HBV Core Protein

Cited by 10 publications

References 17 publications

Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate

Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate

Synthesis, X-Ray Crystal Structure, Hirshfeld Surface Analysis, and Molecular Docking Study of Novel Hepatitis B (HBV) Inhibitor: 8-Fluoro-5-(4-fluorobenzyl)-3-(2-methoxybenzyl)-3,5-dihydro-4H-pyrimido[5,4-b]indol-4-one

Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

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