Aim: Despite the serious side effects, analgesics acting on opioid receptors are still considered the best way to get antinociception. Matrix metalloproteinases, a large family of zinc-dependent proteases implicated in many pathological conditions, such as diabetes and osteoarthritis, are also involved in inflammation and pain. Methodology & results: Looking for evidence of possible interactions of opioid pathways and inflammation mediators, molecular modeling studies of a series of recently developed μ-opioid receptor benzomorphanic agonists together with biological data on pain and inflammation molecular targets, al- lowed us to hypothesize a possible correlation between μ-opioid receptor system and MMP-9. Conclusion: A new compound, (-)-MML1017, emerged as a possible dual-acting agent able to interact selectively and potently with the two molecular targets.
Molecular modeling and biological studies show that some μ-opioid receptor agonists might elicit analgesia acting as MMP-9 inhibitors
	
	
	
		
		
		
		
		
	
	
	
	
	
	
	
	
		
		
		
		
		
			
			
			
		
		
		
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
						
							
							
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
			
			
				
				
					
					
					
					
						
							
						
						
					
				
				
				
				
				
				
				
				
				
				
				
			
			
		
		
		
		
	
Simone Ronsisvalle
						
						
						
							Conceptualization
;Angelo SpadaroMembro del Collaboration Group
;Barbara TomaselloMembro del Collaboration Group
;Livia BasileMembro del Collaboration Group
;Silvia FranchiniMembro del Collaboration Group
;Marcella RenisMembro del Collaboration Group
;Salvatore GuccioneMembro del Collaboration Group
;Lucia Crascı`Membro del Collaboration Group
;Anna Maria PanicoMembro del Collaboration Group
	
		
		
	
			2019-01-01
Abstract
Aim: Despite the serious side effects, analgesics acting on opioid receptors are still considered the best way to get antinociception. Matrix metalloproteinases, a large family of zinc-dependent proteases implicated in many pathological conditions, such as diabetes and osteoarthritis, are also involved in inflammation and pain. Methodology & results: Looking for evidence of possible interactions of opioid pathways and inflammation mediators, molecular modeling studies of a series of recently developed μ-opioid receptor benzomorphanic agonists together with biological data on pain and inflammation molecular targets, al- lowed us to hypothesize a possible correlation between μ-opioid receptor system and MMP-9. Conclusion: A new compound, (-)-MML1017, emerged as a possible dual-acting agent able to interact selectively and potently with the two molecular targets.| File | Dimensione | Formato | |
|---|---|---|---|
| Ronsisvalle FutureMedChem.pdf solo gestori archivio 
											Descrizione: FutureMedChem 2019
										 
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