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;Angelo Spadaro;Barbara Tomasello;Livia Basile;Silvia Franchini;Marcella Renis;Salvatore Guccione;Lucia Crascı`;Anna Maria Panico
2019

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.
drug discovery • inflammation • MMP-9 inhibitors • molecular modeling • MOR agonists • multitarget drugs • pain
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/363766
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