AUTHOR=Ibrahim Alhussein A. , Ali Korany A. , Hafez Naglaa A. Abdel , Elsayed Mohamed A. , Mohamed Khalid M. H. , Hosni Hanaa M. , Amr Abd El-Galil E. , Elsayed Elsayed A. 

TITLE=Synthesis and Characterization of Macrocyclic Chiral Tröger’s Base Phenhomazine Candidates as Anticancer Agent

JOURNAL=Frontiers in Chemistry

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2020.633065

DOI=10.3389/fchem.2020.633065

ISSN=2296-2646

ABSTRACT=<p>1,4,7,10-Tetraoxa[10](2,8)trögerophane <bold>5</bold> was synthesized from its corresponding precursors. Heating of <bold>2</bold> with p-nitrophenoxide afforded bis(p-nitrophenyl)ether <bold>3</bold>, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether <bold>4</bold>. Treatment of <bold>4</bold> with paraformaldehyde and triflouroacetic anhydride gave trögerophane <bold>5</bold>. Reaction of <bold>5</bold> with trifluroacetic anhydride afforded phenhomazine derivative <bold>6</bold>, which was treated with potassium carbonate to afford tetrahydrophenhomazine <bold>7</bold>. Finally, reaction of <bold>7</bold> with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds <bold>8, 9</bold> and <bold>10</bold>, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC<sub>50</sub> of 92.7 µg/ml.</p>