Elucidation of binding interactions and mechanism of Fludarabine with dsDNA via multispectroscopic and molecular docking studies

Objective: To evaluate the therapeutic efficacy and underlying molecular mechanisms of Bauhiniastatin-1 (BSTN1) to alleviate adiposity in diet-induced obese rodent model and in 3T3-L1 cells.Methods: BSTN1 was purified and confirmed through HPLC. In-vitro experiments such as MTT assay, Oil Red-O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis were performed in 3T3-L1 cells in the presence and absence of BSTN1. In animal experiments, rats were divided into Group-I: normal pellet diet-fed, Group-II: HFD-fed, Groups-III, IV and V: HFD-fed BSTN1 (1.25, 2.5, and 5 mg/kg.b.wt./day/rat)-treated and Group-VI: HFD-fed Orlistat-treated. The rats were fed either normal diet or high fat diet (HFD) for 18 weeks and water ad-libitum. BSTN1 was orally administered from 13th week onwards to the selected HFD-fed groups. Body composition parameters, biochemical assays, histopathology examination and western blot analysis were performed to identify the predicted targets related to obesity. Molecular docking studies threw light on the binding interactions of BSTN1 against PPAR-γ, FAS and AMPK.Results: BSTN1 at 20 μM significantly (p < 0.001) inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells. A conspicuous down-regulation in the mRNA expression levels of PPAR-γ, FAS and SREBP1 was observed but AMPK expression remained unchanged in BSTN1 treated 3T3-L1 cells. A substantial decrease in body weight gain, fat percent, total body fat, serum and liver lipid profile (except high-density lipoprotein), glucose, insulin and insulin resistance in BSTN1 treated rats was noticed in a dose dependent manner. In BSTN1 (5 mg/kg.b.wt.)-treated groups significantly (p < 0.01) elevated plasma adiponectin level but reduced leptin level as well as fall in serum AST and ALT were noticed. Further, the disturbed structural integrity and architecture of adipose and hepatic tissues due to high fat diet feeding were considerably recovered with BSTN1 treatment. Down-regulation in the protein expression level of PPAR-γ and activation of AMPK through phosphorylation was observed in BSTN1 treated rats than the untreated. Molecular docking studies revealed strong binding interactions of BSTN1 against PPAR-γ and AMPK and thus supported the experimental results.Conclusion: Taken together, the results suggest that BSTN1 could be a promising pharmacological molecule in the treatment of obesity and dyslipidemia.

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Crude extract and isolated bioactive compounds from Notholirion thomsonianum (Royale) Stapf as multitargets antidiabetic agents: in-vitro and molecular docking approaches

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03443-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mater H. Mahnashi ◽

Yahya S. Alqahtani ◽

Ali O. Alqarni ◽

Bandar A. Alyami ◽

Muhammad Saeed Jan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Molecular Docking ◽

Research Work ◽

Docking Studies ◽

Common Disease ◽

World Population ◽

Binding Interactions ◽

Molecular Docking Studies ◽

Crude Extracts

Abstract Background Diabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus. Methods The crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B. Results Initially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC50 values of 67, 70, < 0.1, 89 and 16 μg/mL against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 respectively. Three compounds (Nt01, Nt02 and Nt03) were isolated from Nt.EtAc of N. thomsonianum. The isolated compounds Nt01, Nt02 and Nt03 exhibited IC50 values of 58.93, 114.93 and 19.54 μM against α-glucosidase, while 56.25, 96.54 and 24.39 μM against α-amylase respectively. Comparatively, the standard acarbose observed IC50 values were 10.60 and 12.71 μM against α-glucosidase, α-amylase respectively. In PTP1B assay, the compounds Nt01, Nt02 and Nt03 demonstrated IC50 values of 12.96, 36.22 and 3.57 μM in comparison to the standard ursolic acid (IC50 of 3.63 μM). The isolated compounds also gave overwhelming results in DPPH assay. Molecular docking based binding interactions for α-glucosidase, α-amylase and PTP1B were also encouraging. Conclusions In the light of current results, it is obvious that N. thomsonianum is potential medicinal plant for the treatment of hyperglycemia. Overall, Nt.EtAc was dominant fraction in all in-vitro activities. Three compounds Nt01, Nt02 and Nt03 were isolated from ethyl acetate fraction. The Nt03 specifically was most potent in all in-vitro assays. The molecular docking studies supported our in-vitro results. It is concluded that N. thomsonianum is a rich source of bioactive antidiabetic compounds which can be further extended to in-vivo based experiments.

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Synthesis, biological evaluation and molecular docking studies on the DNA and BSA binding interactions of palladium(II) and platinum(II) complexes featuring amides of tetrazol-1-yl- and tetrazol-5-ylacetic acids

Polyhedron ◽

10.1016/j.poly.2018.10.038 ◽

2019 ◽

Vol 158 ◽

pp. 36-46 ◽

Cited By ~ 3

Author(s):

Elena A. Popova ◽

Aleksandra V. Protas ◽

Anastasiya V. Mukhametshina ◽

Gayane K. Ovsepyan ◽

Roman V. Suezov ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Binding Interactions ◽

Molecular Docking Studies ◽

Bsa Binding

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Searching for Potential Novel BCR-ABL Tyrosine Kinase Inhibitors Through G-QSAR and Docking Studies of Some Novel 2-Phenazinamine Derivatives

Current Computer - Aided Drug Design ◽

10.2174/1573409914666181022142934 ◽

2020 ◽

Vol 16 (5) ◽

pp. 501-510

Author(s):

Mayura Kale ◽

Gajanan Sonwane ◽

Yogesh Choudhari

Keyword(s):

Molecular Docking ◽

Tyrosine Kinase ◽

Anticancer Activity ◽

Statistical Significance ◽

External Validation ◽

Docking Studies ◽

Binding Interactions ◽

Standard Drug ◽

Molecular Docking Studies ◽

Abl Tyrosine Kinase

Background: The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity and selectivity over specific BCR-ABL Tyrosine kinase. Methods: This has been achieved through G-QSAR and molecular docking studies. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2. 2D and structures of ligands were drawn by using Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using semi-empirical method called MOPAC. The protein structure was downloaded as PDB file from RCSC protein data bank. PYMOL was used for studying the binding interactions. The G-QSAR models generated were found to possess training (r2=0.8074), cross-validation (q2=0.6521), and external validation (pred_r2=0.5892) which proved their statistical significance. Accordingly, the newly designed series of 2-phenazinamines viz., 3-chloro-4-aryl-1-(phenazin-7-yl) azetidin-2-ones (4a-4e) were subjected to wet lab synthesis. Alternatively, docking st udies were also conducted which showed binding interactions of some derivatives with > 30% higher binding energy values than the standard anticancer drug imatinib. The lower energy values obtained for these derivatives indicate energetically favorable interaction with protein binding site as compared to standard imatinib. Results: G-QSAR and molecular docking studies predicted better anticancer activity for the synthesized azitidine derivatives of 2-phenazinamines (4a-4e) as compared to standard drug. Conclusion: It is therefore surmised that the molecular manipulations at appropriate sites of these derivatives suggested by structure activity relationship data will prove to be beneficial in raising anticancer potential.

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