Anticancer potential of phytochemicals against breast cancer: Molecular docking and simulation approach

Ahmed, Bilal; Ashfaq, Usman Ali; Qamar, Muhammad Tahir ul; Ahmad, Matloob

doi:10.3329/bjp.v9i4.20412

Cited by 25 publications

(9 citation statements)

References 7 publications

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“…The preferred binding of glycyrrhizin is at the central palm, sandwiching the finger and thumb domains, adjacent to the active substrate-binding pocket, which makes a strong bond with many vital catalytic residues. In contrast to the cocrystallized peptide inhibitor VIR251, which has a different conformation and binds to a different substrate cavity site, the glycyrrhizin-binding site is close to the VIR251 site [ 62 ]. In terms of interacting binding residues, the glycyrrhizin correlates more with the GRL0617 inhibitor of SAR-CoV-2 PLpro [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

Computational Determination of Potential Multiprotein Targeting Natural Compounds for Rational Drug Design Against SARS-COV-2

et al. 2021

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SARS-CoV-2 caused the current COVID-19 pandemic and there is an urgent need to explore effective therapeutics that can inhibit enzymes that are imperative in virus reproduction. To this end, we computationally investigated the MPD3 phytochemical database along with the pool of reported natural antiviral compounds with potential to be used as anti-SARS-CoV-2. The docking results demonstrated glycyrrhizin followed by azadirachtanin, mycophenolic acid, kushenol-w and 6-azauridine, as potential candidates. Glycyrrhizin depicted very stable binding mode to the active pocket of the Mpro (binding energy, −8.7 kcal/mol), PLpro (binding energy, −7.9 kcal/mol), and Nucleocapsid (binding energy, −7.9 kcal/mol) enzymes. This compound showed binding with several key residues that are critical to natural substrate binding and functionality to all the receptors. To test docking prediction, the compound with each receptor was subjected to molecular dynamics simulation to characterize the molecule stability and decipher its possible mechanism of binding. Each complex concludes that the receptor dynamics are stable (Mpro (mean RMSD, 0.93 Å), PLpro (mean RMSD, 0.96 Å), and Nucleocapsid (mean RMSD, 3.48 Å)). Moreover, binding free energy analyses such as MMGB/PBSA and WaterSwap were run over selected trajectory snapshots to affirm intermolecular affinity in the complexes. Glycyrrhizin was rescored to form strong affinity complexes with the virus enzymes: Mpro (MMGBSA, −24.42 kcal/mol and MMPBSA, −10.80 kcal/mol), PLpro (MMGBSA, −48.69 kcal/mol and MMPBSA, −38.17 kcal/mol) and Nucleocapsid (MMGBSA, −30.05 kcal/mol and MMPBSA, −25.95 kcal/mol), were dominated mainly by vigorous van der Waals energy. Further affirmation was achieved by WaterSwap absolute binding free energy that concluded all the complexes in good equilibrium and stability (Mpro (mean, −22.44 kcal/mol), PLpro (mean, −25.46 kcal/mol), and Nucleocapsid (mean, −23.30 kcal/mol)). These promising findings substantially advance our understanding of how natural compounds could be shaped to counter SARS-CoV-2 infection.

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Section: Resultsmentioning

confidence: 99%

Computational Determination of Potential Multiprotein Targeting Natural Compounds for Rational Drug Design Against SARS-COV-2

et al. 2021

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“…Apart from its anti-inflammatory effect, this compound has also been shown to possess antiulcer, antimalarial and anti-plasmodial properties 45 . Similarly, Kushenol K has also been reported to be a potent anticancer agent, inhibiting estrogen α-receptor and thus eventually reducing over expression of estrogen in breast cancer 46 . While role of Kushenol W has not yet been investigated in any scientific study.…”

Section: Discussionmentioning

confidence: 96%

Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus

Qamar

Maryam

Muneer

et al. 2019

Sci Rep

Self Cite

114

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Emergence of Dengue as one of the deadliest viral diseases prompts the need for development of effective therapeutic agents. Dengue virus (DV) exists in four different serotypes and infection caused by one serotype predisposes its host to another DV serotype heterotypic re-infection. We undertook virtual ligand screening (VLS) to filter compounds against DV that may inhibit inclusively all of its serotypes. Conserved non-structural DV protein targets such as NS1, NS3/NS2B and NS5, which play crucial role in viral replication, infection cycle and host interaction, were selected for screening of vital antiviral drug leads. A dataset of plant based natural antiviral derivatives was developed. Molecular docking was performed to estimate the spatial affinity of target compounds for the active sites of DV’s NS1, NS3/NS2B and NS5 proteins. The drug likeliness of the screened compounds was followed by ADMET analysis whereas the binding behaviors were further elucidated through molecular dynamics (MD) simulation experiments. VLS screened three potential compounds including Canthin-6-one 9-O-beta-glucopyranoside, Kushenol W and Kushenol K which exhibited optimal binding with all the three conserved DV proteins. This study brings forth novel scaffolds against DV serotypes to serve as lead molecules for further optimization and drug development against all DV serotypes with equal effect against multiple disease causing DV proteins. We therefore anticipate that the insights given in the current study could be regarded valuable towards exploration and development of a broad-spectrum natural anti-dengue therapy.

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“…So far, 399 studies have been shown on ClinicalTrials. gov for TNBC and are under phase III investigation ( Ahmed et al, 2014 ; Riaz et al, 2017 ; Won and Spruck, 2020 ). The concept of immune checkpoint inhibitors is to halt regulatory immune checkpoints and thus activate anti-tumor responses.…”

Section: Signaling Pathwaysmentioning

confidence: 99%

Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence

Almansour

2022

Front. Mol. Biosci.

199

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Triple-negative breast cancer (TNBC) is a kind of breast cancer that lacks estrogen, progesterone, and human epidermal growth factor receptor 2. This cancer is responsible for more than 15–20% of all breast cancers and is of particular research interest as it is therapeutically challenging mainly because of its low response to therapeutics and highly invasive nature. The non-availability of specific treatment options for TNBC is usually managed by conventional therapy, which often leads to relapse. The focus of this review is to provide up-to-date information related to TNBC epidemiology, risk factors, metastasis, different signaling pathways, and the pathways that can be blocked, immune suppressive cells of the TNBC microenvironment, current and investigation therapies, prognosis, and the role of artificial intelligence in TNBC diagnosis. The data presented in this paper may be helpful for researchers working in the field to obtain general and particular information to advance the understanding of TNBC and provide suitable disease management in the future.

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Anticancer potential of phytochemicals against breast cancer: Molecular docking and simulation approach

Cited by 25 publications

References 7 publications

Computational Determination of Potential Multiprotein Targeting Natural Compounds for Rational Drug Design Against SARS-COV-2

Computational Determination of Potential Multiprotein Targeting Natural Compounds for Rational Drug Design Against SARS-COV-2

Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus

Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence

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