scholarly journals Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Somaye Karimian ◽  
Fatemeh Kazemi ◽  
Mahshid Attarroshan ◽  
Maryam Gholampour ◽  
Shiva Hemmati ◽  
...  
Keyword(s):  
Cell Line ◽  
Inhibitory Activity ◽  
Binding Mode ◽  
Positive Control ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
Melanoma B16f10 ◽  
Synthesis And Biological Evaluation

AbstractA series of symmetrical azine derivatives containing different substituted benzyl moieties were designed, synthesized, and evaluated for their inhibitory activity against tyrosinase. The results showed that compounds 3e, 3f, 3h, 3i, 3j, and 3k possess effective tyrosinase inhibition with IC50 values ranging from 7.30 μM to 62.60 μM. Particularly, compounds 3f displayed around three-fold improvement in the potency (IC50 = 7.30 ± 1.15 μM) compared to that of kojic acid (IC50 = 20.24 ± 2.28 μM) as the positive control. Kinetic study of compound 3f confirmed uncompetitive inhibitory activity towards tyrosinase indicating that it can bind to enzyme–substrate complex. Next, molecular docking analysis was performed to study the interactions and binding mode of the most potent compound 3f in the tyrosinase active site. Besides, the cytotoxicity of 3f, as well as its potency to reduce the melanin content were also measured on invasive melanoma B16F10 cell line. Also, 3f exhibited above 82% cell viability in the A375 cell line at 10 µM. Consequently, compounds 3f could be introduced as a potent tyrosinase inhibitor that might be a promising candidate in the cosmetics, medicine, and food industry.

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

scholarly journals Design, synthesis and biological evaluation of 1,2,3-triazole based 2-aminobenzimidazoles as novel inhibitors of LasR dependent quorum sensing in Pseudomonas aeruginosa

RSC Advances ◽  
2019 ◽  
Vol 9 (50) ◽  
pp. 29273-29292 ◽  
Author(s):  
Singireddi Srinivasarao ◽  
Adinarayana Nandikolla ◽  
Shashidhar Nizalapur ◽  
Tsz Tin Yu ◽  
Sravani Pulya ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Cell Line ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Hek 293 ◽  
Line P ◽  
Synthesis And Biological Evaluation ◽  
Hek 293 Cell Line

Out of 40 benzimdazoles, 12 exhibited potent QSI activity against P. aeruginosa6p, most active QSI is docked to LasR and is less toxic against HEK 293 cell line.

scholarly journals Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 10 ◽  
Author(s):  
Hehua Xiong ◽  
Jianxin Cheng ◽  
Jianqing Zhang ◽  
Qian Zhang ◽  
Zhen Xiao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Docking Simulation ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Mcf 7

A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

Design, synthesis and biological evaluation of 2-amino-N-(2-aminophenyl)thiazole-5-carboxamide derivatives as novel Bcr-Abl and histone deacetylase dual inhibitors

RSC Advances ◽  
2016 ◽  
Vol 6 (105) ◽  
pp. 103178-103184 ◽  
Author(s):  
Xin Chen ◽  
Shuang Zhao ◽  
Yichao Wu ◽  
Yadong Chen ◽  
Tao Lu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Inhibitory Activity ◽  
Biological Evaluation ◽  
Design Approach ◽  
Design Synthesis ◽  
Dual Inhibitors ◽  
Synthesis And Biological Evaluation ◽  
Novel Design

A novel design approach: combination of Bcr-Abl and HDAC inhibitory activity in one molecule to produce dual inhibitors.

scholarly journals Design, synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-c]quinazoline derivatives as novel phosphatidylinositol 3-kinase and histone deacetylase dual inhibitors

RSC Advances ◽  
2017 ◽  
Vol 7 (82) ◽  
pp. 52180-52186 ◽  
Author(s):  
Yichao Wu ◽  
Weichen Dai ◽  
Xin Chen ◽  
Aixin Geng ◽  
Yadong Chen ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Inhibitory Activity ◽  
Biological Evaluation ◽  
Design Approach ◽  
Phosphatidylinositol 3 Kinase ◽  
Design Synthesis ◽  
Dual Inhibitors ◽  
Quinazoline Derivatives ◽  
Synthesis And Biological Evaluation ◽  
Novel Design

A novel design approach by combination of PI3K and HDAC inhibitory activity in one molecule to produce dual inhibitors.

scholarly journals Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long Tang ◽  
Jianchun Jiang ◽  
Guoqiang Song ◽  
Yajing Wang ◽  
Ziheng Zhuang ◽  
...  
Keyword(s):  
Small Molecules ◽  
Inhibitory Activity ◽  
Structural Modification ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
H Nmr ◽  
Lead Compounds ◽  
Activity Test ◽  
Synthesis And Biological Evaluation ◽  
C Nmr

AbstractA series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.

Design, synthesis and biological evaluation of (1,3-diphenyl-1H-pyrazol-4-yl) methyl benzoate derivatives as potential BRAFV600E inhibitors

RSC Advances ◽  
2014 ◽  
Vol 4 (95) ◽  
pp. 52702-52711 ◽  
Author(s):  
Ya-Juan Qin ◽  
Man Xing ◽  
Ya-Liang Zhang ◽  
Jigar A. Makawana ◽  
Ai-Qin Jiang ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Biological Evaluation ◽  
Methyl Benzoate ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation ◽  
Potent Inhibitory Activity ◽  
Benzoate Derivatives

A series of (1,3-diphenyl-1H-pyrazol-4-yl) methyl benzoate derivatives (6a–10d) were designed and synthesized and evaluated as BRAFV600 inhibitors. Among them, compound 10a showed the most potent inhibitory activity against A375, WM266.4 and BRAFV600Ein vitro with IC50 values of 1.36 μM, 0.94 μM and 0.11 μM, respectively.

scholarly journals Design, Synthesis and Biological Evaluation of New Piperazin-4-yl-(acetyl-thiazolidine-2,4-dione) Norfloxacin Analogues as Antimicrobial Agents

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3959 ◽  
Author(s):  
Marc ◽  
Araniciu ◽  
Oniga ◽  
Vlase ◽  
Pîrnău ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Binding Mode ◽  
Biological Properties ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Bacterial Strains ◽  
Design Synthesis ◽  
Parent Molecule ◽  
Synthesis And Biological Evaluation

 In an effort to improve the antimicrobial activity of norfloxacin, a series of hybrid norfloxacin–thiazolidinedione molecules were synthesized and screened for their direct antimicrobial activity and their anti-biofilm properties. The new hybrids were intended to have a new binding mode to DNA gyrase, that will allow for a more potent antibacterial effect, and for activity against current quinolone-resistant bacterial strains. Moreover, the thiazolidinedione moiety aimed to include additional anti-pathogenicity by preventing biofilm formation. The resulting compounds showed promising direct activity against Gram-negative strains, and anti-biofilm activity against Gram-positive strains. Docking studies and ADMET were also used in order to explain the biological properties and revealed some potential advantages over the parent molecule norfloxacin.

scholarly journals Design, Synthesis and Biological Evaluation of Isoxazole-Based CK1 Inhibitors Modified with Chiral Pyrrolidine Scaffolds

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 873 ◽  
Author(s):  
Andreas Luxenburger ◽  
Dorian Schmidt ◽  
Chiara Ianes ◽  
Christian Pichlo ◽  
Marc Krüger ◽  
...  
Keyword(s):  
Binding Mode ◽  
Biological Evaluation ◽  
Crystallographic Analysis ◽  
Structure Based Drug Design ◽  
Design Synthesis ◽  
Atp Binding Site ◽  
Cellular Assays ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds ◽  
Synthesis And Biological Evaluation

In this study, we report on the modification of a 3,4-diaryl-isoxazole-based CK1 inhibitor with chiral pyrrolidine scaffolds to develop potent and selective CK1 inhibitors. The pharmacophore of the lead structure was extended towards the ribose pocket of the adenosine triphosphate (ATP) binding site driven by structure-based drug design. For an upscale compatible multigram synthesis of the functionalized pyrrolidine scaffolds, we used a chiral pool synthetic route starting from methionine. Biological evaluation of key compounds in kinase and cellular assays revealed significant effects of the scaffolds towards activity and selectivity, however, the absolute configuration of the chiral moieties only exhibited a limited effect on inhibitory activity. X-ray crystallographic analysis of ligand-CK1δ complexes confirmed the expected binding mode of the 3,4-diaryl-isoxazole inhibitors. Surprisingly, the original compounds underwent spontaneous Pictet-Spengler cyclization with traces of formaldehyde during the co-crystallization process to form highly potent new ligands. Our data suggests chiral “ribose-like” pyrrolidine scaffolds have interesting potential for modifications of pharmacologically active compounds.

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