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Malaria kills approximately 1 million people a year, mainly in sub-Saharan Africa. Essential steps in the life cycle of the parasite are the development of gametocytes, as well as the formation of oocysts and sporozoites, in theAnopheles mosquito vector. Preventing transmission of malaria through the mosquito is necessary for the control of the disease; nevertheless, the vast majority of drugs in use act primarily against the blood stages. The study described herein focuses on the assessment of the transmission-blocking activities of potent antierythrocytic stage agents derived from the 4(1H )-quinolone scaffold. In particular, three 3-alkyl- or 3-phenyl-4(1H )-quinolones (P4Qs), one 7-(2-phenoxyethoxy)-4(1H )-quinolone (PEQ), and one 1,2,3,4-tetrahydroacridin-9(10H )-one (THA) were assessed for their transmission-blocking activity against the mosquito stages of the human malaria parasite (Plasmodium falciparum ) and the rodent parasite (P. berghei ). Results showed that all of the experimental compounds reduced or prevented the exflagellation of male gametocytes and, more importantly, prevented parasite transmission to the mosquito vector. Additionally, treatment with ICI 56,780 reduced the number of sporozoites that reached theAnopheles salivary glands. These findings suggest that 4(1H )-quinolones, which have activity against the blood stages, can also prevent the transmission ofPlasmodium to the mosquito and, hence, are potentially important drug candidates to eradicate malaria.

4-(1 H )-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10 H )-Ones Prevent the Transmission of Plasmodium falciparum to Anopheles freeborni