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Efficient Nitric Oxide Scavenging by Urea-Functionalized Push-Pull Chromophore Modulates NO-Mediated Diseases
Himadri Shekar Roy1, Neethu K M2, Swati Rajput3
1Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali, 140306, Punjab, India.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|July 11, 2023
Summary
New urea-functionalized chromophores act as nitric oxide (NO) scavengers, converting into stable NONOates. These molecules show promise for sensing and treating NO-mediated diseases.
Area of Science:
- Chemistry
- Biomedical Science
- Materials Science
Background:
- Excess nitric oxide (NO) contributes to various pathological conditions.
- Current strategies to inhibit NO production have shown limited clinical success.
- Developing effective NO scavengers is crucial for managing NO-mediated diseases.
Purpose of the Study:
- To develop novel urea-functionalized chromophores as nitric oxide (NO) scavengers.
- To investigate the mechanism of NO scavenging and the properties of the resulting products.
- To evaluate the potential therapeutic applications of these novel molecules in NO-mediated conditions.
Main Methods:
- Synthesis of urea-functionalized push-pull chromophores with 1,1,4,4-tetracyanobuta-1,3-dienes (TCBD) or expanded TCBD (eTCBD).
- Nuclear Magnetic Resonance (NMR) studies to elucidate the reaction mechanism upon NO binding.
- In vitro evaluation of NO scavenging activity using LPS-activated cells.
- In vivo assessment of therapeutic efficacy in carrageenan-induced paw edema and corneal injury models.
- Characterization of the emissive properties of Urea-eTCBD for sensing applications.
Main Results:
- Urea-functionalized chromophores effectively scavenge excess NO, forming stable NONOates.
- Urea-eTCBD exhibits unique emissive properties, enabling its use as an in vitro NO-sensor.
- Cytocompatible Urea-eTCBD rapidly inactivates NO released from activated cells.
- Therapeutic efficacy demonstrated in preclinical models of inflammation and injury.
Conclusions:
- Urea-functionalized chromophores represent a promising strategy for scavenging excess NO.
- Urea-eTCBD offers dual functionality as a NO sensor and therapeutic agent.
- These findings support the exploration of such molecules for diverse NO-mediated diseases.
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