Investigation of the newly characterized baimantuoluoamide a and baimantuoluoamide b alkaloids as potential cyclin-dependent kinase 4 (CDK4) inhibitors using molecular docking and molecular dynamics simulations

Gurushankar, K.; Rimac, Hrvoje; Потемкин, В. А.; Grishina, Maria

doi:10.1016/j.molstruc.2021.129925

Cited by 18 publications

(5 citation statements)

References 54 publications

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“…The maximum number of minimization cycles was set at 5,000, with an energy gradient convergence threshold of 0.001 kJ/mol/Å [37,38] . This extensive MD simulation provided valuable insights into the dynamic behaviour and stability of the TC2/5HT4 complex [39,40,41] …”

Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

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Computational Evidence for the Anticancer Activity of Phytochemical Constituents of Terminalia Chebula: An In‐Silico Attempt

Dusi,

Saminathan,

Sivakalai

et al. 2024

ChemistrySelect

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Natural compounds represent Secondary metabolites shaped and endorsed by nature over countless years, showcasing both unique chemical variety and a corresponding range of bioactivities, along with drug‐like attributes. Plant‐derived remedies are projected to comprise approximately 25 % of pharmaceuticals in developed nations. Terminalia chebula earns its title as the “King of medicines” due to its multifaceted pharmacological properties. The phytochemical elements within Terminalia chebula were assessed for their interaction with the human dihydrofolate reductase enzyme (5HT4.pdb) due to its significant role in the development of colorectal cancer. The American Cancer Society provides updated CRC statistics based on incidence from population‐based cancer registries and mortality from the National Center for Health Statistics. In 2023, approximately 153,020 individuals will be diagnosed with CRC and 52,550 will die from the disease, including 19,550 cases and 3750 deaths in individuals younger than 50 years. The compounds TC2 (−8.61 Kcal/mol), TC15 (−7.02 Kcal/mol), and TC23 (−6.98 Kcal/mol) demonstrated higher glide scores. Additionally, TC2 (−71.21 Kcal/mol), TC12 (−101.63 Kcal/mol), TC15 (−81.40 Kcal/mol), and TC29 (−77.47 Kcal/mol) exhibited stronger binding affinities (ΔG Bind) to the target. Based on the outcomes of both docking and MM‐GBSA analyses, TC2 was selected for further investigation via molecular dynamics (MD) simulations, which illustrated the stability of the TC2/5HT4 complex. Among the top‐ranked compounds, TC2 adhered to Lipinski's guidelines for drug‐likeness without any violations. Inhibiting the human DHFR enzyme indirectly hampers the progression of colon cancer. The findings from this in‐silico investigation serve as a foundational basis for potential in vitro and in vivo research.

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Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

“…[37,38] This extensive MD simulation provided valuable insights into the dynamic behaviour and stability of the TC2/5HT4 complex. [39,40,41]…”

Section: Compmentioning

confidence: 99%

Computational Evidence for the Anticancer Activity of Phytochemical Constituents of Terminalia Chebula: An In‐Silico Attempt

Dusi,

Saminathan,

Sivakalai

et al. 2024

ChemistrySelect

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“…To bridge the gap in knowledge and complement in vitro and in vivo assays, in silico and computational analyses (or simply molecular docking studies) have become new and important experimental tools to predict molecular interactions between plant metabolites and cellular factors. Using this technology, Gurushankar et al [ 15 ] studied the potential of newly characterised alkaloids baimantuoluoamide A and baimantuoluoamide B (from plant species such as Datura metel L.) as CDK4 inhibitors. CDK4, together with CDK6, is bound and activated by D-type cyclins for the G1-to-S phase transition of the cell cycle [ 16 ].…”

Section: Anticancer Mechanismsmentioning

confidence: 99%

“…p16 and p19 are inhibitors of CDK4/6 [ 16 ]. With respect to baimantuoluoamide B–CDK4 interaction, amino acid residues Phe93, Asp99, and Ile12 were involved, along with Lys35, which is involved in CDK4 inhibition [ 15 ]. Both baimantuoluoamide A and baimantuoluoamide B interact with the non-conserved residues of CDK4 in the ATP binding pocket, which are involved in selective CDK4 inhibition.…”

Section: Anticancer Mechanismsmentioning

confidence: 99%

Anticancer Mechanisms of Bioactive Compounds from Solanaceae: An Update

Nkwe

Lotshwao

Rantong

et al. 2021

Cancers

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Plants continue to provide unlimited pharmacologically active compounds that can treat various illnesses, including cancer. The Solanaceae family, besides providing economically important food plants, such as potatoes and tomatoes, has been exploited extensively in folk medicine, as it provides an array of bioactive compounds. Many studies have demonstrated the anticancer potency of some of the compounds, but the corresponding molecular targets are not well defined. However, advances in molecular cell biology and in silico modelling have made it possible to dissect some of the underlying mechanisms. By reviewing the literature over the last five years, we provide an update on anticancer mechanisms associated with phytochemicals isolated from species in the Solanaceae plant family. These mechanisms are conveniently grouped into cell cycle arrest, transcription regulation, modulation of autophagy, inhibition of signalling pathways, suppression of metabolic enzymes, and membrane disruption. The majority of the bioactive compounds exert their antiproliferative effects by inhibiting diverse signalling pathways, as well as arresting the cell cycle. Furthermore, some of the phytochemicals are effective against more than one cancer type. Therefore, understanding these mechanisms provides paths for future formulation of novel anticancer drugs, as well as highlighting potential areas of research.

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“…The MM/GBSA method was used to examine the baimantuoluoamide B binding on a per-residue basis and the top donating amino acid residues was found. The findings showed that baimantuoluoamide B is a promising hit molecule that can be used to grow selective CDK4 inhibitors in the future (Gurushankar et al 2021). Based on the theoretical efficacy, analyze their experimental capability for nanoparticle synthesis using D. metel.…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic analysis of plant trace element incorporated silver nanoparticles synthesis from Datura metel l.

Krishnamoorthy

Chinnaiah

Kannan

et al. 2023

Indones. J. Biotechnol.

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Here in we report, silver nanoparticles (Ag NPs) prepared from leaf extract of Datura metel L. via green synthesis method. Datura metel L. is an herbal medicinal plant of solanaceae family. The as - prepared Ag NPs characterized employing UV-Vis spectrometer, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDAX) techniques. The appearance of Surface Plasmon Resonance (SPR) peak at 415 nm suggested that creation of Ag NPs in UV-Vis spectrum. XRD pattern showed face centered cubic crystal structure of Ag NPs with organometallic complex phase. Peaks in FTIR spectrum reveal the existence of biomolecules. SEM image illustrate their clastic rock morphology and EDAX profile authenticate the company of Ag and plant trace element. The Cyclic voltammetry (CV), Choronopotentiometry, and Electrochemical impedance spectroscopy (EIS) analysis were performed as prepared Ag electrode. The specific capacitance of 267.59 F/g at 0.5 A/g and cyclic retention of 83.7% after charge-discharge 5000 cycles are obtained. Hence this material could be utilized as Supercapacitor energy storage devices.

show abstract

Investigation of the newly characterized baimantuoluoamide a and baimantuoluoamide b alkaloids as potential cyclin-dependent kinase 4 (CDK4) inhibitors using molecular docking and molecular dynamics simulations

Cited by 18 publications

References 54 publications

Computational Evidence for the Anticancer Activity of Phytochemical Constituents of Terminalia Chebula: An In‐Silico Attempt

Computational Evidence for the Anticancer Activity of Phytochemical Constituents of Terminalia Chebula: An In‐Silico Attempt

Anticancer Mechanisms of Bioactive Compounds from Solanaceae: An Update

Spectroscopic analysis of plant trace element incorporated silver nanoparticles synthesis from Datura metel l.

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