Synthesis and antiplasmodial activity of novel phenanthroline derivatives: An in vivo study

Abstract

<strong><em>Objective(s)</em></strong>: Due to the rapid increased drug resistance to Plasmodium parasites, an urgent need to achieve new antiplasmodial drugs is felt. Therefore, in this study, the new synthetic phenanthroline derivatives were synthesized with antiplasmodial activity.<br /> <strong><em>Materials and Methods: </em></strong>A series of 1,10-phenanthroline derivatives containing amino-alcohol and amino-ether substituents were synthesized via facile procedures, starting with 5,6-epoxy-1,10-phenanthroline. Their antiplasmodial activity was then evaluated using Peter's 4-day suppressive test against <em>Plasmodium berghei</em>-infected mice (ANKA strain). Furthermore, the mean survival time of the mice treated with synthetic compounds was compared with the negative control group.<br /> <strong><em>Results:</em></strong> The results demonstrated that the compounds 6-(3-(dibutylamino)propylamino)-5,6-dihydro-1,10-phenanthroline-5-ol (<strong>7b</strong>) at the dose of 150 mg/kg/day and 4-(1,10-phenanthroline-5-yloxy)-<em>N,N</em>-dipropylbutan-1-amine (<strong>8b</strong>) at the dose of 15 mg/kg/day have 90.58% and 88.32% suppression, respectively. All synthetic compounds prolonged the mean survival time of treated mice in comparison with negative control groups, indicating the <em>in vivo</em> antiplasmodial activity of these new compounds.<br /> <strong><em>Conclusion:</em></strong> The present study is the first attempt to achieve new, effective synthetic compounds based on phenanthroline scaffold with the antiplasmodial activity. However, more research is needed to optimize their antimalarial activity.