Evaluation of plant-derived semi-synthetic molecules against BRD3-BD2 protein: a computational strategy to combat breast cancer

Kumar, Sachin; Bhardwaj, Vijay Kumar; Singh, Rahul; Das, Pralay; Purohit, Rituraj

doi:10.1039/d1me00183c

Cited by 12 publications

(7 citation statements)

References 40 publications

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“…Cluster analysis is used to determine the sets of structures that share similar conformational features, using the MD simulations 49,50 . Cluster analysis manifested that all selected complexes carried 51 clusters (Figure 5, Figure S6, and Table S5).…”

Section: Resultsmentioning

confidence: 99%

Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Kumar

Bhardwaj

Singh

et al. 2022

J of Cellular Biochemistry

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Dengue is a prominent viral disease transmitted by mosquitoes to humans that affects mainly tropical and subtropical countries worldwide. The global spread of dengue virus (DENV) is mainly occurred by Aedes aegypti and Aedes albopictus mosquitoes. The dengue virus serotypes-2 (DENV-2) is a widely prevalent serotype of DENV, that causes the hemorrhagic fever and bleeding in the mucosa, which can be fatal. In the life cycle of DENV-2, a structural capsid (DENV-2 C) protein forms the nucleocapsid assembly and bind to the viral progeny RNA. For DENV-2 maturation, the nucleocapsid is a vital component. We used virtual ligand screening to filter out the best in-house synthesized acridinedione analogs (DSPD molecules) that could efficiently bind to DENV-2 C protein. The molecular docking and dynamics simulations studies were performed to analyze the effect of DSPD molecules on DENV-2 C protein after binding. Our findings showed that DSPD molecules strongly interacted with DENV-2 C protein, as evident from molecular interactions and several time-dependent molecular dynamics-driven analyses. Moreover, this study was also supported by the thermodynamic binding free energy and steered molecular dynamics simulations. Therefore, we intend to suggest that the DSPD3 molecule could be used as a potential therapeutic molecule against dengue complications as compared to the cocrystallized inhibitor ST-148. However, further studies are required to demonstrate the ability of DSPD3 to induce DENV-2 C tetramer formation.

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Section: Resultsmentioning

confidence: 99%

Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Kumar

Bhardwaj

Singh

et al. 2022

J of Cellular Biochemistry

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“…Therefore, proper identification of tumor subsets is necessary because it may affect the prognosis of patients, and molecular detection should be considered (Abd Hamid et al, 2020). Previous studies have explored the effects of target factors on protein structure and function via molecular docking and long‐term molecular dynamics simulation, which have provided new ideas for our subsequent experiments (S. Kumar et al, 2022). Further studies are needed to confirm these prognostic and immune infiltration‐related markers and identify their roles in the prognosis and treatment of KIRC.…”

Section: Discussionmentioning

confidence: 99%

“…To obtain information regarding the enrichment of DEGs among the different risk subgroups, we performed an enrichment analysis to obtain some meaningfully related functions, signaling pathways, and BPs. A total of 9551 DE-lncRNAs (6819 upregulated and 2732 downregulated) were identified to be differentially expressed between the high-risk and low-risk groups (Supporting Information: - subsequent experiments (S. Kumar et al, 2022). Further studies are needed to confirm these prognostic and immune infiltration-related markers and identify their roles in the prognosis and treatment of KIRC.…”

Section: Enrichment Analysis Of Differentially Expressed Lncrnas In D...mentioning

confidence: 99%

Bioinformatics analysis of markers based on m⁶A related to prognosis combined with immune invasion of renal clear cell carcinoma

Liu

Zhuang

et al. 2022

Cell Biology International

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The incidence rate of renal cell carcinoma (RCC) is about 3% of all adult cancers. Of these, the Kidney clear cell renal cell carcinoma (KIRC) is the most common type, accounting for about 70%-75% of RCC. KIRC is difficult to be detected in time clinically. KIRC still has no effective treatment at this stage. We combined highthroughput bioinformatics analysis to obtained the structural sequence transcriptome data, relevant clinical information, and m 6 A gene map of KIRC patients from genomics TCGA database. Pearson's correlation analysis was used to explore m 6 A related gene long noncoding RNAs (lncRNAs), and then univariate Cox regression analysis was performed to screen the prognostic role of KIRC patients. Lasso-Cox regression was performed to establish the lncRNAs risk model associated with m 6 A.LINC02154 and AC016773.2, Z98200.2, AL161782.1, EMX2OS, AC021483.2, CD27-AS1, AC006213.3 were iidentif. Compared with the low-risk group, the overall survival of patients in the high-risk group was significantly worse. Analyzing whether there are differences in immune cells between high-risk and low-risk subgroups. There were CD4 memory resting, Monocytes, Macrophages M1, Dendritic cells activated, Mast cells resting, which had higher infiltrations in the low-risk group. We performed Go enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and gene set enrichment analysis enrichment analysis. Overall, our results suggest that the component of m6A-related lncRNAs in the prognostic signal may be a key mediator in the immune microenvironment of KIRC, which represents a promising therapeutic effect.

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“…Such therapies could imply inhibitors of cyclin dependent kinases (CDK) [ 14 ] or novel targets may be based on novel predictive biomarkers. A new development in this context is the design of bifunctional degrader molecules for bromodomain-containing proteins, such as BRD3 [ 15 , 16 ], which target the estrogen signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration

et al. 2022

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Background: Tamoxifen-adapted MCF-7-Tam cells represent an in-vitro model for acquired tamoxifen resistance, which is still a problem in clinics. We here investigated the correlation of microRNA-, mRNA- and eukaryotic initiation factors (eIFs) expression in this model. Methods: MicroRNA- and gene expression were analyzed by nCounter and qRT-PCR technology; eIFs by Western blotting. Protein translation mode was determined using a reporter gene assay. Cells were transfected with a miR-1972-mimic. Results: miR-181b-5p,-3p and miR-455-5p were up-, miR-375, and miR-1972 down-regulated and are significant in survival analysis. About 5% of the predicted target genes were significantly altered. Pathway enrichment analysis suggested a contribution of the FoxO1 pathway. The ratio of polio-IRES driven to cap-dependent protein translation shifted towards cap-dependent initiation. Protein expression of eIF2A, -4G, -4H and -6 decreased, whereas eIF3H was higher in MCF-7-Tam. Significant correlations between tamoxifen-regulated miRNAs and eIFs were found in representative breast cancer cell lines. Transfection with a miR-1972-mimic reverses tamoxifen-induced expression for a subset of genes and increased proliferation in MCF-7, but reduced proliferation in MCF-7-Tam, especially in the presence of 4OH-tamoxifen. Migration was inhibited in MCF-7-Tam cells. Translation mode remained unaffected. Conclusions: miR-1972 contributes to the orchestration of gene-expression and physiological consequences of tamoxifen adaption.

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Evaluation of plant-derived semi-synthetic molecules against BRD3-BD2 protein: a computational strategy to combat breast cancer

Abstract: BRD3-BD2 protein belongs to the bromodomain and extra-terminal domain (BET) protein family. It is an epigenetic molecule that is over-expressed and contributes to the development of breast cancer by regulating...

Cited by 12 publications

References 40 publications

Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Bioinformatics analysis of markers based on m⁶A related to prognosis combined with immune invasion of renal clear cell carcinoma

Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration

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Evaluation of plant-derived semi-synthetic molecules against BRD3-BD2 protein: a computational strategy to combat breast cancer

Abstract: BRD3-BD2 protein belongs to the bromodomain and extra-terminal domain (BET) protein family. It is an epigenetic molecule that is over-expressed and contributes to the development of breast cancer by regulating...

Cited by 12 publications

References 40 publications

Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue

Bioinformatics analysis of markers based on m6A related to prognosis combined with immune invasion of renal clear cell carcinoma

Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration

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Bioinformatics analysis of markers based on m⁶A related to prognosis combined with immune invasion of renal clear cell carcinoma