Abstract
The pH equilibria and the zinc ion and bovine serum albumin (BSA) binding behavior of curcumin and two chemically modified curcumins (CMCs), namely 4-methoxycarbonylcurcumin (CMC 2.5) and 4-phenylaminocarbonyl bis-demethoxy curcumin (CMC 2.24), were studied, in order to understand the basis of their differential effects on the zinc-enzyme matrix metalloproteinases (MMPs) as well as the effect of charge state on their behavior in vivo. Moreover, all three compounds transform rapidly in the pH range 5-10, CMC 2.5 largely in one step, and CMC 2.24 and curcumin first in a rapid process to an intermediate form that still displays an enolic and two phenolic hydrogen-ion equilibria, and then more slowly to forms absorbing primarily in the lower UV and lacking the strong absorbance in the visible characteristic of the enol-centered chromophore. The binding of these compounds in one of the hydrophobic pockets of the major transport protein, serum albumin, was therefore studied. CMC 2.24 binds more strongly to BSA than curcumin, with a dissociation constant of 0.56±0.08 μM compared to 1.32±0.17 μM. Binding to BSA shifts the decomposition half-lives from tens of seconds to tens of hours. The zero-time acid dissociation constants (pKa) for species H3D, H2D-, and HD2- are 8.41, 9.94 and 11.2; 6.98, 8.40 and 9.8; and 6.50 and 8.82 ; for curcumin, CMC 2.24, and CMC 2.5 respectively (there is no distinguishable pKa3 for CMC 2.5). Zn2+ binds most strongly to CMC 2.24 compared to CMC 2.5 and curcumin, with dissociation constants of 0.77±0.02, 1.88±0.07, and 1.39±0.09 mM. The increased acidity and Zn2+ and BSA affinities of CMC 2.24 correlate with its greater biological activity.
Keywords: Matrix metalloproteinase, curcumin, pKa, zinc-binding, bovine serum albumin binding, time-dependence, UV-visible absorbance and equilibria, fluorescence quenching, Förster energy transfer
Current Medicinal Chemistry
Title:pKa, Zinc- and Serum Albumin-Binding of Curcumin and Two Novel Biologically- Active Chemically-Modified Curcumins
Volume: 19 Issue: 25
Author(s): Yu Zhang, Lorne M. Golub, Francis Johnson and Arnold Wishnia
Affiliation:
Keywords: Matrix metalloproteinase, curcumin, pKa, zinc-binding, bovine serum albumin binding, time-dependence, UV-visible absorbance and equilibria, fluorescence quenching, Förster energy transfer
Abstract: The pH equilibria and the zinc ion and bovine serum albumin (BSA) binding behavior of curcumin and two chemically modified curcumins (CMCs), namely 4-methoxycarbonylcurcumin (CMC 2.5) and 4-phenylaminocarbonyl bis-demethoxy curcumin (CMC 2.24), were studied, in order to understand the basis of their differential effects on the zinc-enzyme matrix metalloproteinases (MMPs) as well as the effect of charge state on their behavior in vivo. Moreover, all three compounds transform rapidly in the pH range 5-10, CMC 2.5 largely in one step, and CMC 2.24 and curcumin first in a rapid process to an intermediate form that still displays an enolic and two phenolic hydrogen-ion equilibria, and then more slowly to forms absorbing primarily in the lower UV and lacking the strong absorbance in the visible characteristic of the enol-centered chromophore. The binding of these compounds in one of the hydrophobic pockets of the major transport protein, serum albumin, was therefore studied. CMC 2.24 binds more strongly to BSA than curcumin, with a dissociation constant of 0.56±0.08 μM compared to 1.32±0.17 μM. Binding to BSA shifts the decomposition half-lives from tens of seconds to tens of hours. The zero-time acid dissociation constants (pKa) for species H3D, H2D-, and HD2- are 8.41, 9.94 and 11.2; 6.98, 8.40 and 9.8; and 6.50 and 8.82 ; for curcumin, CMC 2.24, and CMC 2.5 respectively (there is no distinguishable pKa3 for CMC 2.5). Zn2+ binds most strongly to CMC 2.24 compared to CMC 2.5 and curcumin, with dissociation constants of 0.77±0.02, 1.88±0.07, and 1.39±0.09 mM. The increased acidity and Zn2+ and BSA affinities of CMC 2.24 correlate with its greater biological activity.
Export Options
About this article
Cite this article as:
Zhang Yu, M. Golub Lorne, Johnson Francis and Wishnia Arnold, pKa, Zinc- and Serum Albumin-Binding of Curcumin and Two Novel Biologically- Active Chemically-Modified Curcumins, Current Medicinal Chemistry 2012; 19 (25) . https://dx.doi.org/10.2174/092986712802884240
DOI https://dx.doi.org/10.2174/092986712802884240 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Cardio-Rheumatology: Two Collaborating Disciplines to Deal with the Enhanced Cardiovascular Risk in Autoimmune Rheumatic Diseases
Current Vascular Pharmacology Volumetric Analysis of the Hypothalamus, Amygdala and Hippocampus in Non-Suicidal and Suicidal Mood Disorder Patients – A Post-Mortem Study
CNS & Neurological Disorders - Drug Targets An Introductory Message from the Editor-in-Chief
Current Vascular Pharmacology The Role of LRRK2 in Neurodegeneration of Parkinson Disease
Current Neuropharmacology Drugs in Pediatric Ischemic Stroke
Current Drug Targets Chronic Inflammatory Disorders and Accelerated Atherosclerosis: Chronic Kidney Disease
Current Pharmaceutical Design CD36 as a Multiple-Ligand Signaling Receptor in Atherothrombosis
Cardiovascular & Hematological Agents in Medicinal Chemistry Smoking and Eye Pathologies. A Systemic Review. Part II. Retina Diseases, Uveitis, Optic Neuropathies, Thyroid-Associated Orbitopathy
Current Pharmaceutical Design The Era of Cerebellar Therapy
Current Neuropharmacology CD31+ Circulating Angiogenic Cell Number and Subtypes are Reduced in Individuals with Chronic Stroke
Current Neurovascular Research Soluble RAGE-Modulating Drugs: State-of-the-Art and Future Perspectives for Targeting Vascular Inflammation
Current Vascular Pharmacology Combined Bazedoxifene and Genistein Ameliorate Ovariectomy-Induced Hippocampal Neuro-Alterations via Activating CREB/BDNF/TrkB Signaling Pathway
Current Molecular Pharmacology Associations between Periodontitis and Systemic Inflammatory Diseases: Response to Treatment
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients
Current Medicinal Chemistry The Failing Heart in Pediatric Dilated Cardiomyopathy Caused by Excessive Water Drinking: A Case Report and Brief Review
New Emirates Medical Journal Dysfunction of Cellular Transporters and Predisposition to Diabetic Nephropathy
Current Diabetes Reviews Interplay Between ACE2 and Angiotensin-(1-7) in the Regulation of Blood Pressure
Current Hypertension Reviews Reviewed and updated Algorithm for Genetic Characterization of Syndromic Obesity Phenotypes
Current Genomics Renal Artery Stenosis: A Unique Disease or a Broad Spectrum of Different Diseases?
Current Hypertension Reviews Resistance Exercise Versus Aerobic Exercise Combined with Metformin Therapy in the Treatment of type 2 Diabetes: A 12-Week Comparative Clinical Study
Endocrine, Metabolic & Immune Disorders - Drug Targets