title: Synthesis and characterizations of novel quinoline derivatives having mixed ligand activities at the kappa and mu receptors: Potential therapeutic efficacy against morphine dependence.
abstract: Based on an established 3D pharmacophore, a series of quinoline derivatives were synthesized. The opioidergic properties of these compounds were determined by a competitive binding assay using (125)I-Dynorphine, (3)H-DAMGO and (125)I-DADLE for kappa, mu, and delta receptors, respectively. Results showed varying degree of activities of the compounds to kappa and mu opioid receptors with negligible interactions at the delta receptor. The compound, S4 was the most successful in inhibiting the two most prominent quantitative features of naloxone precipitated withdrawal symptoms - stereotyped jumping and body weight loss. Determination of IC(50) of S4 revealed a greater affinity towards mu compared to kappa receptor. In conclusion, quinoline derivatives of S4 like structure offer potential tool for treatment of narcotic addictions.
authors.affiliation: Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Jadavpur, Kolkata, India.
authors.forename: Ishani
authors.initials: I
authors.lastname: Deb
authors.forename: Priyankar
authors.initials: P
authors.lastname: Paira
authors.forename: Abhijit
authors.initials: A
authors.lastname: Hazra
authors.forename: Sukdeb
authors.initials: S
authors.lastname: Banerjee
authors.forename: Pradip Kumar
authors.initials: PK
authors.lastname: Dutta
authors.forename: Nirup Bikash
authors.initials: NB
authors.lastname: Mondal
authors.forename: Sumantra
authors.initials: S
authors.lastname: Das
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D003164:Competitive Bidding; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D009021:Morphine Dependence / Q000188:drug therapy*; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C470913:2-(2-methylquinolin-4-ylamino)-N-phenylacetamide; D000083:Acetanilides; D000634:Aminoquinolines; D008024:Ligands; D009292:Narcotic Antagonists; D011804:Quinolines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu