Tyrosinase Inhibitory Activity, 3D QSAR, and Molecular Docking Study of 2,5-Disubstituted-1,3,4-Oxadiazoles

In continuation with our research program, in search of potent enzyme tyrosinase inhibitor, a series of synthesized 2,5-disubstituted 1,3,4-oxadiazoles have been evaluated for enzyme tyrosinase inhibitory activity. Subsequently, 3D QSAR and docking studies were performed to find optimum structural requirements for potent enzyme tyrosinase inhibitor from this series. The synthesized 20 compounds of 2,5-disubstituted-1,3,4-oxadiazole series were screened for mushroom tyrosinase inhibitory activity at various concentrations by enzyme inhibition assay. The percentage enzyme inhibition was calculated by recording absorbance at 492 nm with microplate reader. 3D QSAR and docking studies were performed using VLife MDS 3.5 software. In the series 2,5-disubstituted-1,3,4-oxadiazoles enzyme tyrosinase inhibitory activity was found to be dose dependent with maximum activity for compounds4c,4h,4m, and4r. 3D QSAR and docking studies revealed that more electropositive and less bulky substituents if placed on 1,3,4-oxadiazole nucleus may result in better tyrosinase inhibitory activity in the series.

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A New Tyrosinase Inhibitor from the Red Alga Symphyocladia latiuscula (Harvey) Yamada (Rhodomelaceae)

Marine Drugs ◽

10.3390/md17050295 ◽

2019 ◽

Vol 17 (5) ◽

pp. 295 ◽

Cited By ~ 7

Author(s):

Pradeep Paudel ◽

Aditi Wagle ◽

Su Hui Seong ◽

Hye Jin Park ◽

Hyun Ah Jung ◽

...

Keyword(s):

Methyl Ether ◽

Inhibitory Activity ◽

Biological Activities ◽

Docking Study ◽

Red Alga ◽

Moderate Activity ◽

Molecular Docking Study ◽

Tyrosinase Inhibitory Activity ◽

Ic50 Values ◽

Catalytic Hydrogen

A marine red alga, Symphyocladia latiuscula (Harvey) Yamada (Rhodomelaceae), is a rich source of bromophenols with a wide array of biological activities. This study investigates the anti-tyrosinase activity of the alga. Moderate activity was demonstrated by the methanol extract of S. latiuscula, and subsequent column chromatography identified three bromophenols: 2,3,6-tribromo-4,5-dihydroxybenzyl methyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). Bromophenols 1 and 3 exhibited potent competitive tyrosinase inhibitory activity against l-tyrosine substrates, with IC50 values of 10.78 ± 0.19 and 2.92 ± 0.04 μM, respectively. Against substrate l-3,4-dihydroxyphenylalanine (l-DOPA), compounds 1 and 3 demonstrated moderate activity, while 2 showed no observable effect. The experimental data were verified by a molecular docking study that found catalytic hydrogen and halogen interactions were responsible for the activity. In addition, compounds 1 and 3 exhibited dose-dependent inhibitory effects in melanin and intracellular tyrosinase levels in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Compounds 3 and 1 were the most effective tyrosinase inhibitors. In addition, increasing the bromine group number increased the mushroom tyrosinase inhibitory activity.

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Thiazole Based Carbohydrazide Derivatives as α-Amylase Inhibitor and Their Molecular Docking Study

Heteroatom Chemistry ◽

10.1155/2019/7502347 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Muhammad Taha ◽

Maryam Irshad ◽

Syahrul Imran ◽

Fazal Rahim ◽

Manikandan Selvaraj ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Study ◽

Docking Studies ◽

Antidiabetic Agent ◽

Molecular Docking Study ◽

Binding Interaction ◽

Structure Activity ◽

Inhibitory Potential ◽

Amylase Inhibitors

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

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Isolation of tetramer stilbenoids from Shorea leprosula Miq., acetylcholinesterase inhibitory activity and molecular docking study

10.1055/s-0039-3399897 ◽

2019 ◽

Author(s):

AS Kamarozaman ◽

N Ahmat ◽

MSM Johari ◽

ZZ Hafiz ◽

MI Adenan ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Study ◽

Molecular Docking Study ◽

Acetylcholinesterase Inhibitory Activity ◽

Shorea Leprosula

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Toward the Identification of Novel Carbonic Anhydrase XIV Inhibitors using 3D-QSAR Pharmacophore Model, Virtual Screening and Molecular Docking Study

Letters in Drug Design & Discovery ◽

10.2174/15701808113106660083 ◽

2014 ◽

Vol 11 (4) ◽

pp. 403-412 ◽

Cited By ~ 1

Author(s):

Tao Liu ◽

Lu Zhou ◽

Taijin Wang ◽

Lufen He ◽

Xiangyang Tang

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Carbonic Anhydrase ◽

Pharmacophore Model ◽

3D Qsar ◽

Docking Study ◽

Molecular Docking Study

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Hetero-Tricyclic Lead Scaffold as Novel PDE5A Inhibitor for Antihypertensive Activity: In Silico Docking Studies

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190214161221 ◽

2019 ◽

Vol 15 (4) ◽

pp. 318-333

Author(s):

Dipak P. Mali ◽

Neela M. Bhatia

Keyword(s):

In Silico ◽

Docking Study ◽

Docking Studies ◽

Antihypertensive Activity ◽

In Silico Docking ◽

Π Stacking ◽

Π Stacking Interaction ◽

Nitrogen Heteroatom ◽

Inhibitory Potential ◽

Vlife Mds

Objective:To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies.Methods:In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software.Results:Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have shown one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds.Conclusion:In silico docking studies revealed that nitrogen-containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds have emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.

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Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization

Current Computer - Aided Drug Design ◽

10.2174/1573409915666181221114107 ◽

2020 ◽

Vol 16 (2) ◽

pp. 155-166

Author(s):

Naveen Dhingra ◽

Anand Kar ◽

Rajesh Sharma

Keyword(s):

Three Dimensional ◽

3D Qsar ◽

Docking Study ◽

Structure Activity Relationship ◽

Docking Studies ◽

Activity Relationship ◽

Structural Requirement ◽

Ligand Interaction ◽

Microtubule Polymerization ◽

Structure Activity

Background: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. Methods: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. Results: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. Conclusion: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

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Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug

Pharmaceuticals ◽

10.3390/ph14070685 ◽

2021 ◽

Vol 14 (7) ◽

pp. 685

Author(s):

Sandra Amanda Kozieł ◽

Monika Katarzyna Lesiów ◽

Daria Wojtala ◽

Edyta Dyguda-Kazimierowicz ◽

Dariusz Bieńko ◽

...

Keyword(s):

Molecular Docking ◽

Serum Proteins ◽

Docking Study ◽

Minor Groove ◽

Docking Studies ◽

Minor Groove Binding ◽

Binding Modes ◽

Groove Binding ◽

Molecular Docking Study ◽

Threading Intercalation

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residues.

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Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

Physical Sciences Reviews ◽

10.1515/psr-2019-0136 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Joshua Oluwasegun Bamidele ◽

George Oche Ambrose ◽

Oluwaseun Suleiman Alakanse

Keyword(s):

Molecular Docking ◽

Liver Toxicity ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Docking Analysis ◽

Computational Docking ◽

Drug Candidates ◽

Expression Rate ◽

Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

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