Saccharide-Linked Dithiocarbamates for Stable Anti-Cancer Copper Complexes
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Solution Overview
Problem
Existing anti-cancer agents like disulfiram face challenges due to insolubility and instability in blood plasma, limiting their effectiveness in cancer treatment, and their metabolites lack chelating ability to form active complexes.
Innovation Solution
Development of saccharide-linked dithiocarbamates that form an active complex in vivo by connecting dithiocarbamates to (poly)saccharides via thioglycosidic bonds, enhancing stability and solubility while maintaining the ability to form a copper complex for anti-cancer activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If disulfiram is used as an anti-cancer agent, then anti-cancer activity is achieved through copper complex formation, but insolubility and instability in blood plasma occur
Solution Approach 1:
The patent introduces a saccharide moiety as an intermediary component that forms a conjugate with dithiocarbamate. This saccharide-linked conjugate acts as a prodrug that stabilizes the dithiocarbamate in blood plasma while maintaining the ability to form active copper complexes. The saccharide portion serves as a protective intermediary that prevents degradation without interfering with the ultimate anti-cancer mechanism.
Solution Approach 2:
The patent modifies the chemical structure of dithiocarbamate by changing its physical and chemical parameters through conjugation with saccharide. This structural modification improves solubility and stability parameters while preserving the essential chelating ability to form copper complexes. The conjugation alters the pharmacokinetic parameters without compromising the pharmacodynamic activity.
2Reliability
If disulfiram is used to treat cancer, then copper complex formation occurs, but rapid metabolism reduces chelating ability
Solution Approach 1:
The patent performs preliminary protection of the dithiocarbamate group by conjugating it with saccharide before administration. This preliminary action prevents premature metabolism and degradation, extending the duration that the compound remains active in the bloodstream. The saccharide-linked prodrug form ensures the dithiocarbamate is available for copper complex formation for a longer period.
3Stability of the object's composition
If S-methyl diethyldithiocarbamate is formed as a metabolite, then stability is improved, but chelation ability is lost
Solution Approach 1:
The patent applies local quality modification by selectively protecting only the dithiocarbamate portion with saccharide conjugation while maintaining the overall stability of the molecule. The saccharide linkage provides local protection against metabolism without affecting the chelating sites. This localized protection allows the molecule to remain stable while preserving its ability to bind copper ions.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The saccharide-linked dithiocarbamates exhibit improved solubility and stability, effectively forming active complexes to target cancer cells, including resistant lines, with enhanced anti-cancer activity.
Implementation Method 1
maintaining the ability to be cleaved by metal ions and the chelating ability dithiocarbamate ligand to form the active copper complex
Data Source
AI summary
The present invention provides a compound, or the pharmaceutically acceptable salts or solvates thereof, for use in the treatment of a subject with cancer, wherein the compound has the general formula (I) wherein each of Rn1 and Rn2 is independently selected from the group consisting of C1-C6 alkyl and C2-C6 alkenyl; A is a (poly)saccharide connected via a thioglycosidic bond; and x is 1 or more. Also provided is a pharmaceutical composition for use in the treatment of a subject with cancer, the pharmaceutical composition comprising the compound of formula (I), optionally further comprising a metal, wherein the pharmaceutical composition is for simultaneous administration of the compound of formula (I) and the metal.