title: Design and synthesis of new series of coumarin-aminopyran derivatives possessing potential anti-depressant-like activity.
abstract: A new series of coumarin based aminopyran derivatives were designed, synthesized and evaluated for their preclinical antidepressant effect on Swiss albino mice. Among the series, compounds 21, 25, 26, 27, 32 and 33 exhibited significant activity profile in forced swimming test (FST). Compound 27 was most efficacious, which at a very low dose of 0.5mg/kg reduced the time of immobility by 86.5% as compared to the standard drug fluoxetine (FXT) which reduced the immobility time by 69.8% at the dose of 20mg/kg, ip. In addition, all active compounds were screened in dose dependent manner (at doses of 0.25, 0.5, 1mg/kg ip) in FST and tail suspension test (TST). Interestingly, all active compounds did not caused any significant alteration of locomotor activity in mice as compared to control, indicating that the hybrids did not produce any motor impairment effects. The results indicate that coumarin-aminopyran derivatives may have potential therapeutic value for the management of mental depression.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: sashidhar123@gmail.com.
authors.forename: Koneni V
authors.initials: KV
authors.lastname: Sashidhara
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Ram K
authors.initials: RK
authors.lastname: Modukuri
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: K
authors.initials: K
authors.lastname: Bhaskara Rao
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: G
authors.initials: G
authors.lastname: Aruna Teja
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Sampa
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute (CSIR-CDRI), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Shubha
authors.initials: S
authors.lastname: Shukla
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003374:Coumarins / Q000737:chemistry*; D003863:Depression / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects*; D011714:Pyrans / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D003374:Coumarins; D011714:Pyrans; D005473:Fluoxetine
keywords: Aminopyran; Coumarin; Depression; Forced swimming test; Locomotor activity; Tail suspension test