Journal ArticleDOI
Biomolecular mode of action of metformin in relation to its copper binding properties.
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The results clearly show that the copper binding energies cannot alone be the cause of the biochemical differentiation between Metf and PDI, and conclude that other factors such as pKa values and hydrophilicity of the compounds play a crucial role in their cellular activity.Abstract:
Metformin (Metf), the most commonly used type 2 diabetes drug, is known to affect the cellular housekeeping of copper. Recently, we discovered that the structurally closely related propanediimidamide (PDI) shows a cellular behavior different from that of Metf. Here we investigate the binding of these compounds to copper, to compare their binding strength. Furthermore, we take a closer look at the electronic properties of these compounds and their copper complexes such as molecular orbital interactions and electrostatic potential surfaces. Our results clearly show that the copper binding energies cannot alone be the cause of the biochemical differentiation between Metf and PDI. We conclude that other factors such as pKa values and hydrophilicity of the compounds play a crucial role in their cellular activity. Metf in contrast to PDI can occur as an anion in aqueous medium at moderate pH, forming much stronger complexes particularly with CuII ions, suggesting that biguanides but not PDI may induce easy oxid...read more
Citations
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Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields
TL;DR: In this paper, the unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio using DFT, MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set.
Journal ArticleDOI
The mechanisms of action of metformin
TL;DR: Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut.
Journal ArticleDOI
Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status
Amy R. Cameron,Vicky L. Morrison,Daniel Levin,Mohapradeep Mohan,Calum Forteath,Craig Beall,Alison D. McNeilly,David J.K. Balfour,Terhi Savinko,Aaron Wong,Benoit Viollet,Kei Sakamoto,Susanna C. Fagerholm,Marc Foretz,Chim C. Lang,Graham Rena +15 more
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus as a source of infection for other animals.
Journal ArticleDOI
Metformin directly acts on mitochondria to alter cellular bioenergetics
TL;DR: It is demonstrated that metformin directly acts on mitochondria to limit respiration and that the sensitivity of cells to meetformin is dependent on their ability to cope with energetic stress.
Journal ArticleDOI
Repurposing metformin: an old drug with new tricks in its binding pockets.
Rosina Pryor,Filipe Cabreiro +1 more
TL;DR: The present review provides a thorough and detailed account of the current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide–protein interactions and focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function.
References
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Journal ArticleDOI
Density‐functional thermochemistry. III. The role of exact exchange
TL;DR: In this article, a semi-empirical exchange correlation functional with local spin density, gradient, and exact exchange terms was proposed. But this functional performed significantly better than previous functionals with gradient corrections only, and fits experimental atomization energies with an impressively small average absolute deviation of 2.4 kcal/mol.
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Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density
TL;DR: Numerical calculations on a number of atoms, positive ions, and molecules, of both open- and closed-shell type, show that density-functional formulas for the correlation energy and correlation potential give correlation energies within a few percent.
Journal ArticleDOI
Density-functional exchange-energy approximation with correct asymptotic behavior.
TL;DR: This work reports a gradient-corrected exchange-energy functional, containing only one parameter, that fits the exact Hartree-Fock exchange energies of a wide variety of atomic systems with remarkable accuracy, surpassing the performance of previous functionals containing two parameters or more.
Journal ArticleDOI
The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals
Yan Zhao,Donald G. Truhlar +1 more
TL;DR: The M06-2X meta-exchange correlation function is proposed in this paper, which is parametrized including both transition metals and nonmetals, and is a high-non-locality functional with double the amount of nonlocal exchange.
Journal ArticleDOI
Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields
TL;DR: In this article, the unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio using DFT, MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set.