Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets

Pandya, Prateek; Agarwal, Lokesh Kr; Gupta, Neelima; Pal, Sourav

doi:10.1016/j.jmgm.2014.09.001

Cited by 40 publications

(25 citation statements)

References 44 publications

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“…Vinblastine is a therapeutic drug for Hodgkin’s disease, lymphocytic lymphoma, histiocytic lymphoma, advanced testicular cancer, advanced breast cancer, Kaposi’s sarcoma and Letterer-Siwe disease [ 111 , 112 ]. Vinblastine has higher affinity for tubulin and causes microtubule depolymerisation [ 113 ].…”

Section: Small Molecules Targeting Sgsmentioning

confidence: 99%

Targeting stress granules: A novel therapeutic strategy for human diseases

Wang

Fan

et al. 2020

Pharmacological Research

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Section: Small Molecules Targeting Sgsmentioning

confidence: 99%

Targeting stress granules: A novel therapeutic strategy for human diseases

Wang

Fan

et al. 2020

Pharmacological Research

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“…Molecular docking plays an important role in structural details about the ligand‐macromolecular complexation . Docking can reveal structural insight into drug interactions with nucleic acids, proteins, and other structural assemblies . These methods are reliable in terms of predicting structural possibilities of fitting a drug/ligand onto a target molecule.…”

Section: Resultsmentioning

confidence: 99%

“…These methods are reliable in terms of predicting structural possibilities of fitting a drug/ligand onto a target molecule. Recently, a combination of molecular docking and quantum mechanical/molecular mechanical methods has also been attempted to explore the interactions between drug‐receptor complexes . In addition to the structural information, these methods also estimate the binding affinity and binding free energy values of drugs with their target molecule.…”

Section: Resultsmentioning

confidence: 99%

“…26,31,49 Docking can reveal structural insight into drug interactions with nucleic acids, proteins, and other structural assemblies. 26,31,[49][50][51] These methods are reliable in terms of predicting structural possibilities of fitting a drug/ligand onto a target molecule.…”

Section: Interaction Of Harmaline With Nucleic Acidsmentioning

confidence: 99%

“…Recently, a combination of molecular docking and quantum mechanical/molecular mechanical methods has also been attempted to explore the interactions between drug-receptor complexes. 51 In addition to the structural information, these methods also estimate the binding affinity and binding free energy values of drugs with their target molecule. The binding affinity values obtained from docking may not always agree completely with the experimental results because of several variables such as the counterion environment, solvent effects, and force field accuracy.…”

Section: Interaction Of Harmaline With Nucleic Acidsmentioning

confidence: 99%

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Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Bhattacharjee

Ghosh

Sarkar

et al. 2017

J of Molecular Recognition

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The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single-stranded (ss) poly(A) > double-stranded calf thymus (CT) DNA > double-stranded poly(G)·poly(C) > clover leaf tRNA . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNA , very weak induced circular dichroism perturbation was seen. The interaction was predominantly exothermic, enthalpy driven, and entropy favored with CT DNA and poly(G)·poly(C), while it was entropy driven with poly(A) and tRNA . Intercalated state of harmaline inside poly(A), CT DNA, and poly(G)·poly(C) was shown by viscometry, ferrocyanide quenching, and molecular docking. All these findings unequivocally pointed out preference of harmaline towards ss poly(A) inducing self-structure formation. Furthermore, harmaline administration caused a significant decrease in proliferation of HeLa and HepG cells with GI of 28μM and 11.2μM, respectively. Nucleic acid fragmentation, cellular ultramorphological changes, decreased mitochondrial membrane potential, upregulation of p53 and caspase 3, generation of reactive oxygen species, and a significant increase in the G /M population made HepG more prone to apoptosis than are HeLa cells.

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Thermodynamic and structural profiles of multi‐target binding of vinblastine in solution

Gopi

Singh

Islam

et al. 2022

J of Molecular Recognition

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Structural information about drug‐receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi‐target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR‐5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR‐5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H‐bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.

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Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets

Cited by 40 publications

References 44 publications

Targeting stress granules: A novel therapeutic strategy for human diseases

Targeting stress granules: A novel therapeutic strategy for human diseases

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Thermodynamic and structural profiles of multi‐target binding of vinblastine in solution

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