Hydrogen Sulfide-Releasing Bisphosphonate Hybrids for Bone Regeneration
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Solution Overview
Problem
Current treatments for osteoporosis primarily inhibit bone resorption but fail to restore lost bone mass, leading to potential increased bone fragility due to suppressed bone formation, necessitating the development of drugs that stimulate bone anabolic functions rather than just inhibiting catabolic processes.
Innovation Solution
Development of compounds combining the anti-catabolic effects of alendronate with the anabolic properties of hydrogen sulfide (H2S) to stimulate bone turnover, specifically through the general formula compounds that release H2S, which modulate mesenchymal stem cell activity and osteoclast function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bisphosphonates are used to inhibit bone resorption, then bone loss is reduced, but bone formation is suppressed leading to increased bone fragility
Solution Approach 1:
The invention combines the anti-catabolic function of alendronate (pyrophosphate group) with the anabolic function of hydrogen sulfide-releasing groups to create hybrid molecules that simultaneously inhibit bone resorption and stimulate bone formation, resolving the contradiction between reducing bone loss and maintaining bone strength
Solution Approach 2:
The patent creates composite molecular structures combining known osteoporosis drugs with H2S-releasing functional groups, resulting in hybrid compounds that exhibit both anti-catabolic and anabolic properties, thereby improving bone quality without increasing fragility
2Reliability
If osteoclast activity is suppressed to prevent bone resorption, then bone mass loss is reduced, but physiological bone turnover mechanisms are prolonged suppressed
Solution Approach 1:
The hybrid molecules provide moderate anti-catabolic action rather than complete suppression, allowing partial osteoclast function to remain active while still preventing excessive bone resorption, thus maintaining physiological bone turnover mechanisms
3Loss of substance
If traditional anti-catabolic drugs are used, then bone resorption is inhibited, but bone neoformation is suppressed
Solution Approach 1:
The invention merges the anti-catabolic effect of alendronate with the anabolic effect of H2S in a single hybrid molecule, enabling simultaneous inhibition of bone resorption and stimulation of bone neoformation
Solution Approach 2:
The patent changes the pharmacological parameters of existing drugs by adding H2S-releasing groups, transforming purely anti-catabolic agents into compounds with dual anti-catabolic and anabolic activities
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
These compounds demonstrate cytoprotective and osteoanabolic effects, promoting bone mineralization while maintaining anti-catabolic functions, offering a more balanced approach to bone health compared to traditional bisphosphonates by enhancing bone deposition and reducing osteoclast activity without excessive suppression.
Implementation Method 1
Hydrogen sulphide (H2S) is a gaseous molecule historically known as a toxic agent. However, in recent years, an important biological role has been attributed to H2S, which is physiologically produced by cells in minimal quantities and performs a gas transmitting function... The Applicants realised, through preliminary studies, that H2S is able to significantly modulate the function and phenotypic differentiation of human bone cells... Preliminary experiments have suggested that H2S functions by stimulating mesenchymal stem cells (MSCs), the precursors of osteoblasts, thereby inducing an increase in the deposition of new bone mineral matrix.
Implementation Method 2
The molecules of the invention have been developed with the aim of coupling the anti-catabolic function of alendronate (due to the pyrophosphate groups) with an anabolic function due to H2S... compounds combining the anti-catabolic effects of alendronate with the anabolic properties of hydrogen sulfide (H2S) to stimulate bone turnover, specifically through the general formula compounds that release H2S
Data Source
AI summary
The invention relates to compounds of general formula (I) and pharmaceutically acceptable salts thereof: (I) wherein Ri is selected from an SCN— group or is an RCONH— group; in particular, where Ri=RCONH, R is selected from an aromatic benzene ring substituted with an SCN— group in the ortho, meta or para position, according to the following formula: SCN— or R is a C1-C4 alkyl chain, substituted with an SCN— group; n can be equal to 0 or else 1. The invention also relates to the use of such compounds for the treatment of osteoporosis and in general of bone pathologies characterized by a progressive loss of bone mass, for example rheumatoid arthritis, hyperparathyroidism or bone tumor metastases.