scholarly journals Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1059 ◽  
Author(s):  
Hongchuan Zhao ◽  
Pu Sun ◽  
Wei Guo ◽  
Yi Wang ◽  
Ao Zhang ◽  
...  
Keyword(s):  
Natural Product ◽  
Inhibitory Activity ◽  
Immune Escape ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Tumor Immune Escape ◽  
Lead Compounds ◽  
Indoleamine 2,3 Dioxygenase ◽  
Promising Target

There is great interest in developing small molecules agents capable of reversing tumor immune escape to restore the body’s immune system. As an immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO-1) is considered a promising target for oncology immunotherapy. Currently, none of IDO-1 inhibitors have been launched for clinical practice yet. Thus, the discovery of new IDO-1 inhibitors is still in great demand. Herein, a series of diverse ortho-naphthaquinone containing natural product derivatives were synthesized as novel IDO-1 inhibitors. Among them, 1-ene-3-ketone-17-hydroxyl derivative 12 exhibited significantly improved enzymatic and cellular inhibitory activity against IDO-1 when compared to initial lead compounds. Besides, the molecular docking study disclosed that the two most potent compounds 11 and 12 have more interactions within the binding pocket of IDO-1 via hydrogen-bonding, which may account for their higher IDO-1 inhibitory activity.

scholarly journals A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4400
Author(s):  
Huda S. Al-Salem ◽  
Md Arifuzzaman ◽  
Hamad M. Alkahtani ◽  
Ashraf N. Abdalla ◽  
Iman S. Issa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Binding Pocket ◽  
Competitive Inhibitor ◽  
Breast Adenocarcinoma ◽  
Type Ii ◽  
Molecular Docking Study ◽  
Biological Targets ◽  
A2780 Cell

Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds 4j (IC50 = 1.51 ± 0.09 µM) and 4k (IC50 = 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound 4e showed considerable cytotoxicity against both tested cell lines, MCF7 (IC50 = 5.46 ± 0.71 µM) and A2780 (IC50 = 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds 4j (IC50 = 0.245 µM) and 4k (IC50 = 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC50 = 0.131 µM). A molecular docking study of 4j and 4k confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.

scholarly journals DNA Topoisomerase I Inhibitory Activity of Quinochalcone C-glycosides from the Florets of Carthamus tinctorius

2017 ◽  
Vol 12 (11) ◽  
pp. 1934578X1701201
Author(s):  
Shi-Jun Yue ◽  
Wen-Xiao Wang ◽  
Cheng Qu ◽  
Lan-Ting Xin ◽  
Yu-Ping Tang ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Dna Cleavage ◽  
Topoisomerase I ◽  
Docking Study ◽  
Carthamus Tinctorius ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Dna Topoisomerase ◽  
Cleavage Complex

The DNA topoisomerase (Topo) I inhibitory activity of six quinochalcone C-glycosides (QCGs) isolated from the florets of Carthamus tinctorius were evaluated in vitro. Among them, anhydrosafflor yellow B (AHSYB, 4) and carthorquinoside B (6) could inhibit DNA Topo I at concentrations as low as 100 μM. Molecular docking study revealed that both of them have the capacity to stabilize Topo I-DNA cleavage complex in silico interacting with the essential binding sites, such as Arg364, Thr718 and TGP11. Besides, both compounds 4 and 6 exhibited no antitumor activity by in vitro cytotoxicity assays.

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

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 295 ◽  
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.

Synthesis, molecular docking study and thymidine phosphorylase inhibitory activity of 3-formylcoumarin derivatives

2018 ◽  
Vol 78 ◽  
pp. 17-23 ◽  
Author(s):  
Muhammad Taha ◽  
Syed Adnan Ali Shah ◽  
Muhammad Afifi ◽  
Syahrul Imran ◽  
Sadia Sultan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Thymidine Phosphorylase ◽  
Docking Study ◽  
Molecular Docking Study

scholarly journals Gymnema Sylvestre A- Potential Inhibitor of COVID-19 Main Protease by MD Simulation Study

2020 ◽  
Author(s):  
Senthil Kumar Subramani ◽  
Yash Gupta ◽  
Manish Manish ◽  
GBKS Prasad
Keyword(s):  
Md Simulation ◽  
Docking Study ◽  
Binding Pocket ◽  
Gymnema Sylvestre ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Strong Candidate ◽  
The Stability ◽  
Potential Inhibitors ◽  
Domain I

Gymnema sylvestre (GS) is one of the herbal plant used since in ancient times. The present study aimed to assess bioactive compounds GS mainly gymnemic acids as potential inhibitors for COVID-19 against Mpro enzyme using a molecular docking study. The docking score observed between -53.4 to - 42.4 of all gymnemic acids and its derivatives. Molecular Dynamics (MD) simulation studies carried out at 100ns supported the stability of GS molecules within the binding pocket. RMSD score of less than 3.6. mainly, our results supported that these GS molecules bind to the domain I & II, and domain II-III linker of 3CLpro enzyme, suggesting its suitability as strong candidate for therapeutic against COVID-19. <br>

scholarly journals Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

2020 ◽  
Author(s):  
abde lina ◽  
Khedidja BENAROUS ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Pantothenic Acid ◽  
Vitamin B1 ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Structural Mechanism ◽  
Discovery Studio ◽  
Main Protease ◽  
Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (M<sup>pro</sup>) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against M<sup>pro</sup>, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of M<sup>pro</sup> with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of M<sup>pro</sup>. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to M<sup>pro</sup>, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.<br>

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