DNA binding affinity of a macrocyclic copper(II) complex: Spectroscopic and molecular docking studies

Background: Adenosine receptors (AR) have emerged as competent and innovative nondopaminergic targets for the development of potential drug candidates and thus constitute an effective and safer treatment approach for Parkinson’s disease (PD). Xanthine derivatives are considered as potential candidates for the treatment Parkinson’s disease due to their potent A2A AR antagonistic properties. Objective: The objectives of the work are to study the impact of substituting N7-position of 8-m/pchloropropoxyphenylxanthine structure on in vitro binding affinity of compounds with various AR subtypes, in vivo antiparkinsonian activity and binding modes of newly synthesized xanthines with A2A AR in molecular docking studies. Methods: Several new 7-substituted 8-m/p-chloropropoxyphenylxanthine analogues have been prepared. Adenosine receptor binding assays were performed to study the binding interactions with various subtypes and perphenazine induced rat catatonia model was used for antiparkinsonian activity. Molecular docking studies were performed using Schrödinger molecular modeling interface. Results: 8-para-substituted xanthine 9b bearing an N7-propyl substituent displayed the highest affinity towards A2A AR (Ki = 0.75 µM) with moderate selectivity versus other AR subtypes. 7-Propargyl analogue 9d produced significantly longlasting antiparkinsonian effects and also produced potent and selective binding affinity towards A2A AR. In silico docking studies further highlighted the crucial structural components required to develop xanthine derived potential A2A AR ligands as antiparkinsonian agents. Conclusion: A new series of 7-substituted 8-m/p-chloropropoxyphenylxanthines having good affinity for A2A AR and potent antiparkinsonian activity has been developed.

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Synthesis, Characterization, DNA Binding, Cleavage, Antibacterial, In vitro Anticancer and Molecular Docking Studies of Ni(II), Cu(II) and Zn(II) Complexes of 3,4,5-Trimethoxy-N-(3-Hydroxy-5-(Hydroxymethyl)-2-Methylpyridin-4-yl)methylene)Benzohydrazide

Arabian Journal for Science and Engineering ◽

10.1007/s13369-021-05562-2 ◽

2021 ◽

Author(s):

Kavitha Ramdas ◽

Ch. Venkata Ramana Reddy ◽

B. Sireesha

Keyword(s):

Molecular Docking ◽

Dna Binding ◽

Docking Studies ◽

Molecular Docking Studies

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Structure elucidation, DNA binding and molecular docking studies of natural compounds isolated from Crateva religiosa leaves

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.131976 ◽

2021 ◽

pp. 131976

Author(s):

Mehtab Parveen ◽

Afroz Aslam ◽

Sharmin Siddiqui ◽

Mohammad Tabish ◽

Chullikkattil P. Pradeep ◽

...

Keyword(s):

Molecular Docking ◽

Dna Binding ◽

Structure Elucidation ◽

Natural Compounds ◽

Docking Studies ◽

Molecular Docking Studies

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A NEW LA(Ⅲ) COMPLEX CONSTRUCTED BY LONG FLEXIBLE LIGAND: CRYSTAL STRUCTURE, DNA BINDING AND MOLECULAR DOCKING STUDIES

Журнал структурной химии ◽

10.26902/jsc_id76145 ◽

2021 ◽

Vol 62 (7) ◽

Author(s):

M.C. Zhu

Keyword(s):

Crystal Structure ◽

Molecular Docking ◽

Dna Binding ◽

Docking Studies ◽

Molecular Docking Studies ◽

Flexible Ligand

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MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC TARGETS OF ALZHEIMER'S DISEASE (AChE AND BChE) USING NATURAL BIOACTIVE ALKALOIDS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.14833 ◽

2016 ◽

Vol 8 (12) ◽

pp. 108

Author(s):

Punabaka Jyothi ◽

Kuna Yellamma

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Binding Affinity ◽

Neurodegenerative Disorder ◽

Biological Activities ◽

Neuropsychiatric Symptoms ◽

Docking Studies ◽

Kcal Mole ◽

Molecular Docking Studies

Objective: Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms, is biochemically characterized by a significant decrease in the brain neurotransmitter Acetylcholine (ACh).Methods: In the present insilico study, six plant bioactive compounds namely Harmol, Vasicine, Harmaline, Harmine, Harmane and Harmalol (from P. Nigellastrum Bunge) were analyzed for their inhibitory role on AChE (Acetylcholinesterase) and BChE (Butyrylcholinesterase) activity by applying the molecular docking studies. Other parameters viz. determination of molecular interaction-based binding affinity values, protein-ligand interactions, Lipinski rule of five, functional properties and biological activities for the above compounds were also calculated by employing the appropriate bioinformatics tools.Results: The results of docking analysis clearly showed that Harmalol has highest binding affinity with AChE (-8.6 kcal/mole) and BChE (-8.0 kcal/mole) but it does not qualified the enzyme inhibitory activity, since it was exerted, and also has least percentage activity on AD and neurodegenerative disease. Whereas, the Harmine has been second qualified binding affinity (-8.4 kcal/mol) and first in other parameters when compared with Harmalol.Conclusion: Based on docking results and other parameters conducted, we are concluding that Harmine is the best compound for further studies to treat AD.Keywords: Alzheimer's disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules

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SUSTAINED RELEASE TABLETS OF SORAFENIB-SILIBININ COMBINATIONS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.27597 ◽

2018 ◽

Vol 10 (5) ◽

pp. 117

Author(s):

Savita Mishra ◽

Sandhya Hora ◽

Vibha Shukla ◽

Mukul Das ◽

Harsha Kharkwal ◽

...

Keyword(s):

Molecular Docking ◽

Drug Release ◽

Sustained Release ◽

Cell Line ◽

Binding Affinity ◽

Drug Combination ◽

Docking Studies ◽

Molecular Docking Studies ◽

Weight Variation

Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma.Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation.Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommendation. The hardness of 20 tablets showed 5-6.5Kg/cm2 for all formulations 5-6.5Kg/cm2. The optimized formulation resulted in 98% drug release after 28 h. The present study reports the synergistic effects of drug combination to inhibit cell growth in HepG2 cell line. Molecular docking studies showed that sorafenib has high binding affinity for B-Raf vascular endothelial growth factor receptor β and protein kinase B. Silibinin showed binding affinity with MAP kinase-11, protein phosphatase 2 A and tankyrase.Conclusion: The present study reports for the first time a novel formulation for sustained release and reduced toxicity of sorafenib with enhanced inhibitory effect of the drug combination on cancerous hepatic cell line as well collaborative mechanism of action for the formulation.

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