Metal–ligand interactions in drug design

Riccardi, Laura; Genna, Vito; Vivo, Marco De

doi:10.1038/s41570-018-0018-6

Cited by 138 publications

(124 citation statements)

References 203 publications

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“…In conclusion, the results presented in this work demonstrate the possibility to rationally program the molecular‐recognition ability of monolayer‐protected nanoparticles. As with protein–ligand recognition studies, we could gradationally mutate the relevant interacting groups in the nanoparticle‐coating molecules in order to tune the affinity of the nanoparticles for salicylate. The effects of these mutations on the affinity and selectivity were predicted by computational simulations and validated by experiments.…”

Section: Figurementioning

confidence: 99%

Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Sun¹,

Riccardi

Biasi³

et al. 2019

Angew Chem Int Ed

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Here,w ed emonstrate the possibility of rationally designing nanoparticle receptors with targeted affinity and selectivity for specific small molecules.W eu sed atomistic molecular-dynamics (MD) simulations to gradually mutate and optimize the chemical structure of the molecules forming the coating monolayer of gold nanoparticles (1.7 nm gold-core size). The MD-directed design resulted in nanoreceptors with a1 0-fold improvement in affinity for the target analyte (salicylate) and a1 00-fold decrease of the detection limit by NMR-chemosensing from the millimolar to the micromolar range.W ecould define the exact binding mode,whichfeatures prolonged contacts and deep penetration of the guest into the monolayer,a sw ell as ad istinct shape of the effective binding pockets characterized by exposed interacting points.

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Section: Figurementioning

confidence: 99%

Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Sun¹,

Riccardi

Biasi³

et al. 2019

Angew Chem Int Ed

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“…[5] These properties, along with the structurald iversity offeredb ym odification of the coordinating ligands, can allow metal-based drugs to exhibit unique mechanisms of action to diverseb iological targets. [6] The use of naturally-occurring bioactive molecules or their derivatives as ligands in the preparation of new metallodrugs can offer the advantageo fi ncorporatingm olecules that already have established pharmacological properties and low systemic toxicity. [7] This is exemplified by the recent interest in the preparation of bioactive metal complexes from curcuminoids;t he polyphenols found in turmeric (Curcuma longa), which exhibitarange of pharmacological activities.…”

Section: Introductionmentioning

confidence: 99%

Bismuth(III) Flavonolates: The Impact of Structural Diversity on Antibacterial Activity, Mammalian Cell Viability and Cellular Uptake

Burke

Stephens

Werrett

et al. 2020

Chemistry A European J

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A series of homoleptic and heteroleptic bismuth(III) flavonolate complexes derived from six flavonols of varying substitution have been synthesised and structurally characterised. The complexes were evaluated for antibacterial activity towards several problematic Gram‐positive (Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus (MRSA), and vancomycin‐resistant Enterococcus (VRE)) and Gram‐negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. The cell viability of COS‐7 (monkey kidney) cells treated with the bismuth flavonolates was also studied to determine the effect of the complexes on mammalian cells. The heteroleptic complexes [BiPh(L)2] (in which L=flavonolate) showed good antibacterial activity towards all of the bacteria but reduced COS‐7 cell viability in a concentration‐dependent manner. The homoleptic complexes [Bi(L)3] exhibited activity towards the Gram‐positive bacteria and showed low toxicity towards the mammalian cell line. Bismuth uptake studies in VRE and COS‐7 cells treated with the bismuth flavonolate complexes indicated that Bi accumulation is influenced by both the substitution of the flavonolate ligands and the degree of substitution at the bismuth centre.

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“…Modeling the dynamic behavior of bounded metal-ligand complex using MD simulation requires a comprehensive understanding of the metal-ligand bonding, thermodynamics and coordination chemistry within the receptor binding sites (Riccardi, Genna, & De Vivo, 2018).…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Exploring Ruthenium-based organometallic inhibitors against Plasmodium Calcium Dependent Kinase 2 (PfCDPK2): a combined ensemble docking, QM paramterization and molecular dynamics study

Patel

Athar²,

Jha

2020

Preprint

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Recent advances in the metal-organic framework (MOF) have accelerated the discovery of novel metal-based anticancer, antibacterial and antimalarial compounds. This is substantiated by many serendipitously discovered metals (Ru, Rh, and Ir) based inhibitors that established the importance of metal inserted into the known organic scaffold. Conversely, it is possible to design novel bioactive compounds by mimicking hypervalent carbon atoms by transition metals. This process can be facilitated by computational drug discovery by treating metal center using optimized parameters that can be used for molecular docking and molecular dynamics simulations. Further, the method can be plugged with high computational power and refined algorithms to interpret chemical phenomena with atomic-level insights. In the present work, we have demonstrated an approach for parameterizing three organometallic ligands (FLL, E52, and staurosporine) using MCPB.py. In particular, we report that E52 and FLL have a better shape complimentary and affinity compared to staurosporine identified inhibitor (staurosporine) against Calcium-dependent protein kinases 2 (CDPK2). This study also revealed that a flexible approach (ensemble) outperforms for the given target with dynamic movements. The calculated MMPBSA energies for staurosporine, FLL and E52 were −66.461 ± 2.192, −67.182 ± 1.971 and −91.339 ± 2.745 kcal/mol respectively.

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Metal–ligand interactions in drug design

Cited by 138 publications

References 203 publications

Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Bismuth(III) Flavonolates: The Impact of Structural Diversity on Antibacterial Activity, Mammalian Cell Viability and Cellular Uptake

Exploring Ruthenium-based organometallic inhibitors against Plasmodium Calcium Dependent Kinase 2 (PfCDPK2): a combined ensemble docking, QM paramterization and molecular dynamics study

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