High throughput virtual screening of cyclooxygenase-2 by using database

Author(s):  
Ravi D ◽  
Chaitanya Kumar K ◽  
Mothilal K ◽  
Mahender K

COX-2 is a type of Non-steroidal mitigating drug (NSAID) that legitimately targets COX-2, a protein liable for irritation and torment. Selectivity for COX-2 decreases the danger of peptic ulceration and is the fundamental component of celecoxib, rofecoxib and different individuals from this medication class. COX-2 selectivity doesn't appear to influence other antagonistic impacts of NSAIDs (most prominently an expanded danger of renal disappointment), and a few outcomes have excited the doubt that there may be an expansion in danger for cardiovascular failure, apoplexy and stroke by a relative increment in thromboxane. The target of this investigation is to screen drug-like compounds from Zinc database and to predict the potency and activity by using Virtual Screening and Molecular Docking Study. The scope of the study extends to predict the feasibility of the compounds for Drug development. Hence, this examination expresses the significance of little particle libraries and their utilization to upgrade drug revelation measure earlier amalgamation. This way to deal with screen original mixes as COX-2 inhibitors from ZINC information base relies upon different boundaries, for example, Lipinski's standard of 5, pharmacophoric bunches appended on the ligand, size of the dataset and compound libraries among others. Additional, exertion can be stretched out to consider the receptor-ligand associations tentatively, and assessment of their organic action would help in planning mixes dependent on simulated screening strategies.

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5190
Author(s):  
Belgin Sever ◽  
Mehlika Dilek Altıntop ◽  
Ahmet Özdemir ◽  
Gülşen Akalın Çiftçi ◽  
Doha E. Ellakwa ◽  
...  

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a–i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a–i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC50 values of 6.43 ± 0.72 μM, 9.62 ± 1.14 μM, and 8.07 ± 1.36 μM, respectively, when compared with erlotinib (IC50 = 17.86 ± 3.22 μM, 19.41 ± 2.38 μM, and 23.81 ± 4.17 μM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC50 value of 2.80 ± 0.52 μM when compared with erlotinib (IC50 = 0.04 ± 0.01 μM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations.


2008 ◽  
Vol 2 (8) ◽  
pp. 325-329 ◽  
Author(s):  
Kotaprolu Naga Sudha ◽  
Mohammed Shakira ◽  
Paturi Prasanthi ◽  
Nalla Sarika ◽  
Ch Narasimha Kumar ◽  
...  

2019 ◽  
Vol 15 (4) ◽  
pp. 277-293 ◽  
Author(s):  
Vivek Asati ◽  
Piyush Ghode ◽  
Shalini Bajaj ◽  
Sanmati K. Jain ◽  
Sanjay K. Bharti

Background: In past few decades, computational chemistry has seen significant advancements in design and development of novel therapeutics. Benzimidazole derivatives showed promising anti-inflammatory activity through the inhibition of COX-2 enzyme. Objective: The structural features necessary for COX-2 inhibitory activity for a series of oxadiazole substituted benzimidazoles were explored through 3D-QSAR, combinatorial library generation (Combi Lab) and molecular docking. Methods: 3D-QSAR (using kNN-MFA (SW-FB) and PLSR (GA) methods) and Combi Lab studies were performed by using VLife MDS Molecular Design Suite. The molecular docking study was performed by using AutoDockVina. Results: Significant QSAR models generated by PLSR exhibited r2 = 0.79, q2 = 0.68 and pred_r2 = 0. 84 values whereas kNN showed q2 = 0.71 and pred_r2 = 0.84. External validation of developed models by various parameters assures their reliability and predictive efficacy. A library of 72 compounds was generated by combinatorial technique in which 11 compounds (A1-A5 and B1-B6) showed better predicted biological activity than the most active compound 27 (pIC50 = 7.22) from the dataset. These compounds showed proximal interaction with amino acid residues like TYR355 and/or ARG120 on COX-2(PDB ID: 4RS0). Conclusion: The present work resulted in the design of more potent benzimidazoles as COX-2 inhibitors with good interaction as compared to reference ligand. The results of the study may be helpful in the development of novel COX-2 inhibitors for inflammatory disorders.


2018 ◽  
Vol 59 (2) ◽  
Author(s):  
A. Vafaee ◽  
◽  
A. Davoodnia ◽  
M.R. Bozorgmehr ◽  
M. Pordel ◽  
...  

2014 ◽  
Vol 84 (4) ◽  
pp. 409-419 ◽  
Author(s):  
Pritam N. Dube ◽  
Shweta S. Bule ◽  
Santosh N. Mokale ◽  
Manoj R. Kumbhare ◽  
Pravin R. Dighe ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document