Molecular Dynamic Simulation Study on Chromones and Flavonoids for the In Silico Designing of a Potential Ligand Inhibiting mTOR Pathway in Breast Cancer

Sharma, Varruchi; Panwar, Anil; Sharma, Anil Kumar

doi:10.1007/s40495-020-00246-1

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…Accordingly, the molecular dynamics (MD) simulation validates the stability of the complex system in polar solution was observed using the parameters of RMSD (root mean square deviation), RMSFs (root means square fluctuations), and radius of gyration [ 64 ]. The MD Simulations are very helpful in identifying potential flavonoids and potent ligands targeting disease therapy [ 65 ]. A constant trend for RMSF was observed in systems.…”

Section: Discussionmentioning

confidence: 99%

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

et al. 2022

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The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.

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Section: Discussionmentioning

confidence: 99%

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

et al. 2022

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“…The designed ligand displayed maximum binding affinity of (Δ G —4.91 kcal/mol). In addition, significant efficacy and safety profile was observed [ 110 ]. Similarly, eight flavonoids isolated from Tephroseris kirilowii were evaluated for breast cancer treatment focusing on the mTOR signaling pathway.…”

Section: Flavonoids Targeting Mtor In Breast Cancer and Chemoresistancementioning

confidence: 99%

Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy

Hussain

Khan

Alam

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cancer is one of the leading causes of death worldwide. Breast cancer is the second leading cause of death in women, with triple-negative breast cancer being the most lethal and aggressive form. Conventional therapies, such as radiation, surgery, hormonal, immune, gene, and chemotherapy, are widely used, but their therapeutic efficacy is limited due to adverse side effects, toxicities, resistance, recurrence, and therapeutic failure. Many molecules have been identified and investigated as potential therapeutic agents for breast cancer, with a focus on various signaling pathways. Flavonoids are a versatile class of phytochemicals that have been used in cancer treatment to overcome issues with traditional therapies. Cell proliferation, growth, apoptosis, autophagy, and survival are all controlled by mammalian target of rapamycin (mTOR) signaling. Flavonoids target mTOR signaling in breast cancer, and when this signaling pathway is regulated or deregulated, various signaling pathways provide potential therapeutic means. The role of various flavonoids as phytochemicals in targeting mTOR signaling pathways in breast cancer is highlighted in this review.

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“…Antroquinonol was used for the de novo generation of ligands. Using Chemsketch (ACD Labs freeware), 27,28 the PDB file was generated for antroquinonol. Using the same file as input, we run the Maestro for the docking of seed molecule on the amino acid residue nearest to the most active site.…”

Section: Designing Of Ligandsmentioning

confidence: 99%

A comparative molecular dynamic simulation study on potent ligands targeting mTOR/FRB domain for breast cancer therapy

Sharma

Panwar²,

Sharma

et al. 2021

Biotech and App Biochem

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Our study aimed to develop and find out the best drug candidate against the mechanistic target of rapamycin (mTOR/FRB) domain having a critical role in the aetiology of breast cancer. The FKBP12‐rapamycin‐binding (FRB) domain in the essential phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been a vital player in the disease progression in breast cancer. By using structure‐based drug designing , the best possible targets have been identified and developed. The three‐dimensional structure of the target protein was generated using I‐TASSER. The ligands were generated against the most suitable target active site using standard tools for active site identification. Furthermore, the seed molecule was drawn using Chemsketch, which was then grown into the pocket using Ligbuilder. The obtained ligands were further validated using online programs for bioavailability and toxicity, followed by molecular dynamic simulations. The study concludes that the equilibrated NVT–NPT complexes indicate LIG2 stability over LIG3. RMSD and RMSF have shown that the complex of LIG2 is more stable than LIG3. LIG2 has the potential antagonistic properties to target the mTOR/FRB domain and has therapeutic implications for breast cancer.

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Molecular Dynamic Simulation Study on Chromones and Flavonoids for the In Silico Designing of a Potential Ligand Inhibiting mTOR Pathway in Breast Cancer

Cited by 12 publications

References 27 publications

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy

A comparative molecular dynamic simulation study on potent ligands targeting mTOR/FRB domain for breast cancer therapy

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