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 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.

Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent, and Evaluation for CDK2 Inhibition Activity

2021 ◽  
Vol 17 ◽  
Author(s):  
Rania Helmy Abd El-Hameed ◽  
Samar Said Fatahala ◽  
Amira Ibrahim Sayed
Keyword(s):  
Cell Lines ◽  
Docking Study ◽  
Binding Pocket ◽  
Kinase Assay ◽  
Benzimidazole Derivatives ◽  
Pharmacological Activities ◽  
Anticancer Compounds ◽  
Anti Cancer ◽  
Hct 116

Background: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules, they can easily interact with biomolecules of living systems. Objective: A series of substituted 2-thiobezimidazoles has been synthesized .Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell-lines. Methods: The spectral data of the synthesized compounds were characterized. Docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib were performed. Results: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in CDK-ATP binding pocket. 3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. Conclusion: Against all tested compounds ; two compounds 3c &3l were found active against two types of cell-lines.

scholarly journals Synthesis and Anticancer Activity Evaluation of Azepinobisindoles; the Isomeric Iheyamine A Derivatives

2019 ◽  
Vol 35 (2) ◽  
pp. 723-731
Author(s):  
Weerachai Phutdhawong ◽  
Sopita Rattanopas ◽  
Jitnapa Sirirak ◽  
Thongchai Taechowisan ◽  
Waya S. Phutdhawong
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cancer ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Activity Evaluation ◽  
Cancer Line

Azepinobisindole derivatives, the isomeric Iheyamine skeleton, was prepared and its anticancer activity evaluation were investigated against two human cancer cell lines, Hepatocellular carcinoma (HepG2) and human cervical cancer line (Hela) as well as the normal cell line (Vero cell line) using MTT assay. The anticancer activity results indicated that 2-methoxy-5-methyl-5H-azepino[2,3-b:4,5-bʹ]diindole was the most active derivative against tested cell lines. Additionally, molecular docking study in silico the possible inhibitory effect of cyclin-dependent kinase 2 (CDK2) by the azepinoindole revealed that all synthesized compounds fit well in the binding cavity of CDK2.

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 Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 717 ◽  
Author(s):  
Na Zhao ◽  
Feifei Yang ◽  
Lina Han ◽  
Yuhua Qu ◽  
Di Ge ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Human Cancer ◽  
Immunoblot Analysis ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines

Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds 6 and 7 displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds, 13a and 13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50 values of 0.36–2.91 µM and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that 13a and 13c dose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover, 13a and 13c arrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound 13c.

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.

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