Synthesis, docking and pharmacological evaluation of novel indole based potential atypical antipsychotics.
A series of substituted indole derivatives have been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypy assays in mice. The compounds 11 and 12 have emerged as important lead compounds showing potential atypical antipsychotic profile. In silico (docking studies) have been carried out to postulate a hypothetical binding model for the target compounds with respect to the dopaminergic D2 and 5-HT2A receptors. Theoretical ADME profiling of the compounds based on selected physicochemical parameters has suggested an excellent compliance with Lipinski's rules. The potential of these compounds to penetrate the blood brain barrier (log BB) was computed through an online software program and the values obtained for the compounds suggest good potential for brain permeation.
University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh, 160014, India. Electronic address: alka.bali@rediffmail.com.
Alka
A
Bali
University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh, 160014, India.
Umesh
U
Sen
University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh, 160014, India.
Tania
T
Peshin
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D062105:Molecular Docking Simulation; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
D014150:Antipsychotic Agents; D007211:Indoles; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2
Atypical antipsychotics; D(2)/5-HT(2A) antagonists; Docking studies; In silico; Indole derivatives; Log BB