Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice

Usama Karama; Mujeeb A Sultan; Abdulrahman I Almansour; Kamal Eldin El-Taher

doi:10.3390/molecules21010061

Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice

Molecules. 2016 Jan 5;21(1):61. doi: 10.3390/molecules21010061.

Authors

Usama Karama¹, Mujeeb A Sultan², Abdulrahman I Almansour³, Kamal Eldin El-Taher⁴

Affiliations

¹ Chemistry Department, College of Science, King Saud University, P. O. Box 2455 Riyadh 11451, Saudi Arabia. Karama@ksu.edu.sa.
² Chemistry Department, College of Science, King Saud University, P. O. Box 2455 Riyadh 11451, Saudi Arabia. Alhosami1983@yahoo.co.uk.
³ Chemistry Department, College of Science, King Saud University, P. O. Box 2455 Riyadh 11451, Saudi Arabia. almansor@ksu.edu.sa.
⁴ Department of Pharmacology, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia. eeltahir@ksu.edu.sa.

Abstract

The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (5) and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (6) as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3) and (4) were successfully synthesized via a [4 + 2] cycloaddition between acrolein and 1,8-dichloroanthracene. The synthesized compounds were investigated for antidepressant activity using the forced swimming test. Compounds (5), (6) and (3) showed significant reduction in the mice immobility indicating significant antidepressant effects. These compounds significantly reduced the immobility times at a dose 80 mg/kg by 84.0%, 86.7% and 71.1% respectively.

Keywords: antidepressants; chlorinated tetracyclic; forced swimming test; synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anthracenes / chemical synthesis*
Anthracenes / chemistry
Anthracenes / pharmacology
Anti-Anxiety Agents / chemical synthesis*
Anti-Anxiety Agents / chemistry
Anti-Anxiety Agents / pharmacology
Antidepressive Agents / chemical synthesis*
Antidepressive Agents / chemistry
Antidepressive Agents / pharmacology
Hydrocarbons, Chlorinated / chemical synthesis*
Hydrocarbons, Chlorinated / chemistry
Hydrocarbons, Chlorinated / pharmacology
Immobility Response, Tonic / drug effects
Maprotiline / chemistry
Maprotiline / pharmacology
Mice
Molecular Structure
Swimming

Substances

1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine
1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine
Anthracenes
Anti-Anxiety Agents
Antidepressive Agents
Hydrocarbons, Chlorinated
Maprotiline
benzoctamine