scholarly journals In-Silico approach for designing novel urea/thiourea and schiff base of quinazolinone derivatives of molecular docking H+/K+-ATPase inhibitors

2021 ◽  
pp. 100186
Author(s):  
Satya Vivek Jaiswal ◽  
Neeraj Agarwal ◽  
Meenu Gupta
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
In Silico ◽  
Atpase Inhibitors ◽  
Quinazolinone Derivatives ◽  
Derivatives Of

scholarly journals Selected Derivatives of Erythromycin B-In Silico and Anti-Malarial Studies

Materials ◽  
2021 ◽  
Vol 14 (22) ◽  
pp. 6980
Author(s):  
Pranab K. Bhadra ◽  
Rachael N. Magwaza ◽  
Niroshini Nirmalan ◽  
Sally Freeman ◽  
Jill Barber ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Bacterial Agent ◽  
Ic50 Values ◽  
Exit Tunnel ◽  
Erythromycin A ◽  
Erythronolide B ◽  
In Silico Molecular Docking ◽  
Derivatives Of

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC50 values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC50 of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities.

scholarly journals Profil Metabolit Daun Kesambi (Schleichera oleosa) Berdasarkan Analisis Histokimia dan In Silico

2021 ◽  
Vol 8 (1) ◽  
pp. 156
Author(s):  
Tintrim Rahayu ◽  
Radita Intan Aisyah Pratiwi ◽  
Nurul Jadid Mubarakati
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Secondary Metabolite ◽  
In Silico ◽  
In Silico Analysis ◽  
Histochemical Analysis ◽  
Active Compounds ◽  
Schleichera Oleosa ◽  
Lupeol Acetate ◽  
Derivatives Of

Kesambi (Schleichera oleosa) is a plant belonging to the Sapindaceae familia. This study aims to determine the secondary metabolite compounds found in kesambi leaves through histochemical analysis and derivatives of active compounds in silico. Descriptive experimental research method was conducted in January using samples of kesambi plants that grow on the island of Madura. Histochemical analysis was carried out by preparing fresh leaves through lower leaf incisions with secondary metabolite detection reagents (CuSO4, FeCl3, Wagner, Sudan III, AlCl3 & FeCl3+NaCO3) then microscopic color changes were observed. In silico testing aims to determine the interaction of active compounds with ER? as a target for ER + breast cancer therapy through molecular docking. Supporting software used is KNApSAcK, Pubchem, Pass Online, PDB ID, PyRx, PyMol and Chimera 1.14. The results showed that through histochemical analysis six secondary metabolite compounds were identified, namely terpenoids, flavonoids, alkaloids, tannins, lipophils and phenols. While in silico analysis, the active compound is scopoletin which is derived from phenol, beta-sitosterol, betulin, betulinic acid, lupeol, lupeol acetate, schleicheol 1&2, schleicherastatin 1-7 which are derivatives of terpenoids. Based on the results of molecular docking, there are interactions of active compounds with 3ERT protein, the compounds that provide the most effective results as candidates for breast cancer drugs are lupeol acetate with a value of Root Mean Square Deviation (RMSD) lb 1,588 Å and ub 2,219 Å . Lupeol acetate compound is predicted to have activity as an Er? inhibitor against ER+ breast cancer. Keywords: Kesambi (Schleichera oleosa), histochemistry, molecular docking and ER?.

Cytotoxicity activity, in silico molecular docking, protein- and DNA-binding study of a new Ni(II) Schiff base complex

2018 ◽  
Vol 71 (16-18) ◽  
pp. 2740-2766 ◽  
Author(s):  
Niladri Biswas ◽  
Sumit Khanra ◽  
Arnab Sarkar ◽  
Shamee Bhattacharjee ◽  
Deba Prasad Mandal ◽  
...  
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
Dna Binding ◽  
In Silico ◽  
Schiff Base Complex ◽  
Binding Study ◽  
Base Complex ◽  
Cytotoxicity Activity ◽  
In Silico Molecular Docking ◽  
Docking Protein

scholarly journals IN SILICO STUDIES ON DIACYL DERIVATIVES OF PHLOROGLUCINOL TO ENHANCE PHARMACODYNAMIC AND PHARMACOKINETIC PROFILES OF 2,4,6-TRIHYDROXY-3-GERANYL-ACETOPHENONE

2021 ◽  
pp. 173-179
Author(s):  
SHEAU WEI CHIONG ◽  
CHEAN HUI NG ◽  
KHOZIRAH SHAARI
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Chain Length ◽  
In Silico ◽  
Van Der Waals ◽  
Side Chains ◽  
Amino Acid Residues ◽  
Pharmacokinetic Profiles ◽  
In Silico Studies ◽  
Derivatives Of

Objective: The purpose of this study was to evaluate the LOX inhibitory activity, and predict the drug likeness properties of designed diacyl derivatives of phloroglucinol, using in silico method. Methods: The designed derivatives were subjected to molecular docking using AUTODOCK while the receptor used in this study was built from SWISS MODEL. Drug likeness properties of the derivatives were calculated by online programs i.e. MOLINSPIRATION and PreADMET. Results: Molecular docking study revealed that designed tHGA derivative with four-carbon chain length exhibited the best binding affinity with the docking scores of -7.26kcal/mol. Three types of binding interactions were observed between the derivatives and the receptor site i.e H-bonding, hydrophobic and Van der Waals interactions. The important amino acid residues involved in H-bonding were Gln495 and Gln697, while other amino acid residues, such as Leu754 and Ile 553, were involved in the Van der Waals interaction. The designed tHGA derivatives were mainly stabilized through hydrophobic interactions with His499, His504, Ile538, Phe557 and Val750. In silico physicochemical calculations predicted that all the designed derivatives passed the Lipinski’s Rule of 5, and have good human intestinal absorption property (HIA>70%). Further, all the designed derivatives showed moderate central nervous system absorption (0.6<BBB<2.0), except for the derivative with a longer (5-Cs) chain length. Conclusion: The findings of the present study suggested that changing the acyl and geranyl side chains of the natural product molecule, tHGA, into two acyl bearing side chains, will improve its pharmacodynamic and pharmacokinetic profiles.

scholarly journals In Vitro and In Silico Evaluation of New 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone as Promising Cyclooxygenase Inhibitors

2021 ◽  
Vol 22 (17) ◽  
pp. 9130
Author(s):  
Krzysztof Peregrym ◽  
Łukasz Szczukowski ◽  
Benita Wiatrak ◽  
Katarzyna Potyrak ◽  
Żaneta Czyżnikowska ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Cyclooxygenase Inhibitors ◽  
Molecular Docking Studies ◽  
Cox 2 ◽  
Derivatives Of

Since long-term use of classic NSAIDs can cause severe side effects related mainly to the gastroduodenal tract, discovery of novel cyclooxygenase inhibitors with a safe gastric profile still remains a crucial challenge. Based on the most recent literature data and previous own studies, we decided to modify the structure of already reported 1,3,4-oxadiazole based derivatives of pyrrolo[3,4-d]pyridazinone in order to obtain effective COX inhibitors. Herein we present the synthesis, biological evaluation and molecular docking studies of 12 novel compounds with disubstituted arylpiperazine pharmacophore linked in a different way with 1,3,4-oxadiazole ring. None of the obtained molecules show cytotoxicity on NHDF and THP-1 cell lines and, therefore, all were qualified for further investigation. In vitro cyclooxygenase inhibition assay revealed almost equal activity of new derivatives towards both COX-1 and COX‑2 isoenzymes. Moreover, all compounds inhibit COX-2 isoform better than Meloxicam which was used as reference. Anti-inflammatory activity was confirmed in biological assays according to which title molecules are able to reduce induced inflammation within cells. Molecular docking studies were performed to describe the binding mode of new structures to cyclooxygenase. Investigated derivatives take place in the active site of COX, very similar to Meloxicam. For some compounds, promising druglikeness was calculated using in silico predictions.

In-silico Designing, ADMET Analysis, Synthesis and Biological Evaluation of Novel Derivatives of Diosmin Against Urease Protein and Helicobacter pylori Bacterium

2019 ◽  
Vol 19 (29) ◽  
pp. 2658-2675 ◽  
Author(s):  
Ritu Kataria ◽  
Anurag Khatkar
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Acetohydroxamic Acid ◽  
Jack Bean Urease ◽  
Zone Of Inhibition ◽  
Jack Bean ◽  
Urease Inhibitory ◽  
H Pylori ◽  
Derivatives Of

Background: Designing drug candidates against the urease enzyme, which has been found responsible for many pathological disorders in human beings as well as in animals, was done by insilico means. Methods: Studies were carried out on a designed library of diosmin derivatives with the help of Schrodinger’s maestro package of molecular docking software against a crystallographic complex of plant enzyme Jack bean urease (PDB ID: 3LA4). Best twelve derivatives of diosmin were selected for synthesis by considering their interaction energy along with docking score and were further investigated for antioxidant, urease inhibitory and Anti-H. pylori activity by in- vitro method along with ADMET analysis. Results: In-vitro results of series concluded compounds D2a, D2d and D7 (IC50 12.6 ± 0.002, 14.14 ± 0.001 and 15.64 ± 0.012 µM respectively in urease inhibition and 5.195 ± 0.036, 5.39 ± 0.020 and 5.64± 0.005 µM in antioxidant behavior against DPPH) were found to be significantly potent with excellent docking score -11.721, -10.795, -10.188 and binding energy -62.674, -63.352, -56.267 kJ/ mol as compared to standard drugs thiourea and acetohydroxamic acid (-3.459, -3.049 and -21.156 kJ/mol and - 17.454 kJ/mol) whereas compounds D2b, D5b, D5d and D6 were found moderate in urease inhibitory activity. Conclusions: Selected candidates from the outcome of in-vitro urease inhibitory were further examined for anti- H. pylori activity by a well diffusion method against H. pylori bacterium (DSM 4867). Compound D2a showed good anti-H. Pylori activity with a zone of inhibition 10.00 ± 0.00 mm and MIC value 500µg/mL as compared to standard drug acetohydroxamic acid having a zone of inhibition 9.00 ± 0.50mm and MIC 1000µg/mL. In- silico studies played an important role in designing the potent ligands against urease protein as well as in explaining the binding pattern of designed and synthesized ligand within the active pocket of jack bean urease protein. ADMET studies were also carried out to check the drug similarity of designed compounds by the means of quikprop module of molecular docking software. Hence, the present investigation studies will provide a new vision for the discovery of potent agents against H. pylori and urease associated diseases.

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