Identification of fosaprepitant as a novel GSTP1 inhibitor through structure-based virtual screening, molecular dynamics simulation, and biological evaluation

2021 ◽  
Author(s):  
Hao Lin ◽  
Wenxiu Sun ◽  
Tao Zeng ◽  
Hengda Li ◽  
Chenming Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Biological Evaluation ◽  
Therapeutic Agents ◽  
Dynamics Simulation ◽  
Glutathione S Transferase ◽  
Promising Target ◽  
Cancer Cell Survival ◽  
Prevention And Therapy

Glutathione S-transferase P1 (GSTP1) is a promising target for cancer prevention and therapy, particularly because of its involvement in promoting cancer cell survival and resistance of tumors to therapeutic agents....

scholarly journals A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 857
Author(s):  
Shailima Rampogu ◽  
Seong Min Kim ◽  
Minky Son ◽  
Ayoung Baek ◽  
Chanin Park ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Biological Evaluation ◽  
Dynamics Simulation ◽  
Promising Target ◽  
Vitro Analysis ◽  
Combinatorial Treatment

DDX3 belongs to RNA helicase family that demonstrates oncogenic properties and has gained wider attention due to its role in cancer progression, proliferation and transformation. Mounting reports have evidenced the role of DDX3 in cancers making it a promising target to abrogate DDX3 triggered cancers. Dual pharmacophore models were generated and were subsequently validated. They were used as 3D queries to screen the InterBioScreen database, resulting in the selection of curcumin that was escalated to molecular dynamics simulation studies. In vitro anti-cancer analysis was conducted on three cell lines such as MCF-7, MDA-MB-231 and HeLa, which were evaluated along with exemestane. Curcumin was docked into the active site of the protein target (PDB code 2I4I) to estimate the binding affinity. The compound has interacted with two key residues and has displayed stable molecular dynamics simulation results. In vitro analysis has demonstrated that both the candidate compounds have reduced the expression of DDX3 in three cell lines. However, upon combinatorial treatment of curcumin (10 and 20 μM) and exemestane (50 μM) a synergism was exhibited, strikingly downregulating the DDX3 expression and has enhanced apoptosis in three cell lines. The obtained results illuminate the use of curcumin as an alternative DDX3 inhibitor and can serve as a chemical scaffold to design new small molecules.

Identification of novel CDK 9 inhibitors based on virtual screening, molecular dynamics simulation, and biological evaluation

Life Sciences ◽  
2020 ◽  
Vol 258 ◽  
pp. 118228
Author(s):  
Mingfei Wu ◽  
Jianfei Han ◽  
Zhicheng Liu ◽  
Yilong Zhang ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Biological Evaluation ◽  
Dynamics Simulation
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