scholarly journals Molecular Docking Study of Biologically Active Ligand and the Insights of Synthesis, Characterization and In Vitro Studies of Derivatives of β-tubulin Polymerization Inhibitor as Antigout Agent

2020 ◽  
Vol 13 (07) ◽  
pp. 756-766
Author(s):  
Vaishali H. Gaikwad
2020 ◽  
Vol 11 (3) ◽  
pp. 3684-3690
Author(s):  
Premalatha E ◽  
Dineshraj R ◽  
Iyanar Kannan ◽  
Bhaarath KS ◽  
Sharavanan TKV

The anti-TB drugs currently in the use are insufficient to address these major health challenges. Hence, it is imperative to discover and develop new and efficient drugs against TB. The enzyme pantothenate synthetase (PS or PanC), necessary for the production of pantothenate (vitamin B5), critical components of fatty acid synthesis, when inhibited will in turn affect the cell wall synthesis of bacilli. In the present study, an attempt will be made to find the drug like molecules from quercetin derivatives prepared in silico to find out possible inhibitors of PanCof M. tuberculosis. The 3D structure of PanC was obtained from RCSB database and quercetin from ZINC database. The derivatives of quercetin were prepared and were docked initially with iGEMDOCK docking tool. The final docking was done in AutoDock vina software. The ADMET properties of the selected ligands were done in admetSAR online server tool. The present study revealed that four derivatives of quercetin has excellent binding with Pantothenate Synthetase (PanC) of M. tuberculosis. These derivatives can be taken for in vitro enzymatic assays for its inhibitory property in the search for new anti-TB drugs.


RSC Advances ◽  
2018 ◽  
Vol 8 (31) ◽  
pp. 17511-17526 ◽  
Author(s):  
Ting-Ting Miao ◽  
Xu-Bing Tao ◽  
Dong-Dong Li ◽  
Hao Chen ◽  
Xiao-Yan Jin ◽  
...  

A series of novel 2-aryl-benzimidazole derivatives of dehydroabietic acid were synthesized. Among them, compound 6j was found to be a potent tubulin polymerization inhibitor.


Author(s):  
Vaishali Gaikwad ◽  
Vaibhav Sabale ◽  
Bhimrao Khade

Colchicine is essentially useful in the treatment of gout. In the present work Colchicine Complexes has been prepared with transition metals viz; Copper(II) [Cu(II)], Zinc (II) [Zn(II)], Cobalt (II) [Co(II)], Nickel (II) [Ni(II)] and those checked for molecular docking, it has been observed that Zn(II) and Ni(II) complex has revealed good binding energy than the parent ligand, the increased binding energy of colchicine metal complexes  indicates that, the tubulin polymerization inhibitor tendency is enhanced, consequently antigout property is also increased. As transition metals have antimicrobial activity in themselves, complexes are also characterized for the antimicrobial activity which is enhanced for Cu(II) and Co(II) metals.


2009 ◽  
Vol 8 (11) ◽  
pp. 3036-3045 ◽  
Author(s):  
Christopher J. Burns ◽  
Emmanuelle Fantino ◽  
Ian D. Phillips ◽  
Stephen Su ◽  
Michael F. Harte ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 184 ◽  
Author(s):  
Anca-Maria Borcea ◽  
Gabriel Marc ◽  
Ioana Ionuț ◽  
Dan C. Vodnar ◽  
Laurian Vlase ◽  
...  

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14α-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.


2020 ◽  
Vol 21 (8) ◽  
pp. 2876 ◽  
Author(s):  
A-Liang Li ◽  
Yun Hao ◽  
Wen-Yan Wang ◽  
Qing-Song Liu ◽  
Yue Sun ◽  
...  

In this study, a series of new indole derivatives of ursolic acid bearing different N-(aminoalkyl)carboxamide side chains were designed, synthesized, and evaluated for their in vitro cytotoxic activities against two human hepatocarcinoma cell lines (SMMC-7721 and HepG2) and normal hepatocyte cell line (LO2) via MTT assay. Among them, compound 5f exhibited the most potent activity against SMMC-7721 and HepG2 cells with IC50 values of 0.56 ± 0.08 μM and 0.91 ± 0.13 μM, respectively, and substantially lower cytotoxicity to LO2 cells. A follow-up enzyme inhibition assay and molecular docking study indicated that compound 5f can significantly inhibit the activity of Topoisomerase IIα. Further mechanistic studies performed in SMMC-7721 cells revealed that compound 5f can elevate the intracellular ROS levels, decrease mitochondrial membrane potential, and finally lead to the apoptosis of SMMC-7721 cells. Collectively, compound 5f is a promising Topoisomerase II (Topo II) inhibitor, which exhibited the potential as a lead compound for the discovery of novel anticancer agents.


2019 ◽  
pp. S51-S58
Author(s):  
A. ŠPIČÁKOVÁ ◽  
V. BAZGIER ◽  
L. SKÁLOVÁ ◽  
M. OTYEPKA ◽  
P. ANZENBACHER

Evaluation of possible interactions with enzymes of drug metabolism is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. Here, focus is given on interactions of three sesquiterpenes (β-caryophyllene oxide (CAO), trans-nerolidol (tNER) and farnesol (FAR)) with CYP3A4. To determine the CYP3A4 activity, specific substrates testosterone (TES) and midazolam (MDZ) were used. In human liver microsomes, the CAO inhibited the MDZ 1´-hydroxylation by mixed type inhibition and Ki 46.6 μM; TES 6-hydroxylation was inhibited more strongly by tNER by the same mechanism and with Ki of 32.5 μM. Results indicated a possibility of different mode of interaction of both compounds within the active site of CYP3A4 and this was why the molecular docking study was done. The docking experiments showed that the studied sesquiterpenes (CAO and tNER) bound to the CYP3A4 active site cause a significant decrease of binding affinity of substrates tested which corresponded well to the inhibition studies. The inhibition observed, however, most probably does not pose a real harm to microsomal drug metabolism as the levels of sesquiterpenes in plasma (assuming the use of these compounds as spices or flavoring additives) does not usually exceed micromolar range. Hence, the interaction of drugs metabolized by CYP3A4 with sesquiterpenes is less probable.


2021 ◽  
Vol 6 (4) ◽  
pp. 292-301
Author(s):  
P.V. Sandhya ◽  
K.S. Femina ◽  
A.V. Pradeep

The biologically active pyrazole clubbed imino naphthyl derivatives have been designed and synthesized from 1-phenyl-3-methoxy phenyl-1H-pyrazol-4-carboxaldehyde and substituted naphthyl amines via acid catalyzed condensation reaction. All the synthesized compounds were well characterized by different spectroscopic and mass spectral techniques. The in vitro antibacterial, antifungal and antituberculosis studies were carried out. The molecular docking study was also done with the software Arguslab 4.0.1. The studied compounds showed moderate to good biological activities both experimentally and theoretically. Geometry optimization, DNA binding interaction and FMO analysis were also investigated with the help of Gaussian 16 package at B3LYP/6-31G(d,p) level.


2020 ◽  
Vol 16 ◽  
Author(s):  
Adinath D. Badar ◽  
Shubham M. Sulakhe ◽  
Mahesh B. Muluk ◽  
Naziya N. M. A. Rehman ◽  
Prashant P. Dixit ◽  
...  

Background: Thiosemicarbazone, 1,2,3-triazole and their derivatives received great pharmaceutical importance due to their prominent biological activities. In the present study, the molecular hybrid thiosemicarbazone-1,2,3-triazoles derivatives were synthesized and screened for their antimicrobial activities. Methods: A series of thiosemicarbazone clubbed with 1,2,3-triazole derivatives were synthesized via click chemistry approach in good yields. The structures of synthesized compounds were assigned by their spectral data. The in vitro antimicrobial activity was performed by the agar well diffusion method. A molecular docking study was performed to identify the possible mode of action of synthesized derivatives. Results: The compounds 5d, 5h, 5i and 5k have exhibited excellent antimicrobial activities against both antibacterial and antifungal pathogens. The active thiosemicarbazone-1,2,3-triazole derivatives have shown excellent binding affinity towards DNA gyrase. Conclusion: The molecular hybrid thiosemicarbazone-1,2,3-triazole derivatives were synthesized. The newly synthesized compounds were evaluated for their antimicrobial activities. Few of the thiosemicarbazone-1,2,3-triazoles derivatives have exhibited good antimicrobial activities. They have been shown excellent binding affinity towards DNA gyrase.


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