Antimalarial, antiproliferative, and apoptotic activity of quinoline-chalcone and quinoline-pyrazoline hybrids. A dual action

A series of quinoline-chalcone (E) -1-[3 or 4-(7-chloroquinolin-4-ylamino) phenyl]-3-(phenyl substituted) prop-2-ene-1-one ( 4 , 5 ), and quinoline-pyrazoline hybrids 7-Chloro- N -[3 or 4-(4,5-dihydro-5-(phenyl-substituted)-1H-pyrazol-3-yl] phenyl) quinoline-4–amine ( 6 , 7 ) were synthesized with the aim of achieving an antimalarial and anticancer dual action. Most of the compounds showed significant inhibition (%>80) of β-hematin formation. The existing structures were tested in vivo as potential antimalarials in mice infected with P. berghei ANKA, chloroquine susceptible strain. Some of the compounds exhibited antimalarial activity comparable to that of chloroquine. Moreover, the compounds induce cell death on two human cancer cell lines (Jurkat E6.1 and HL60) without affecting the primary culture of human lymphocytes. Flow cytometry analysis confirmed the increase in apoptotic cell death after 24 h. Based on the structural analysis, these quinoline hybrids represent new compounds potentially useful for malaria end leukemia treatments.