AQ-13

AQ-13 is an investigational antimalarial drug that is structurally similar to chloroquine but with a shorter diaminoalkane side chain. It's being developed specifically to address chloroquine-resistant Plasmodium falciparum infections, which have become widespread in malaria-endemic regions[3][5]. ## Chemical Structure and Properties AQ-13 is a 4-aminoquinoline derivative with the chemical formula C16H22ClN3 (as free base) or C16H22ClN3.2ClH (as dihydrochloride salt)[2][5][7]. Its IUPAC name is 7-chloro-N-[3-(diethylamino)propyl]quinolin-4-amine dihydrochloride[2]. The molecular weight of the free base is 291.819 g/mol, while the dihydrochloride salt weighs 364.74 g/mol[5][7]. ## Mechanism of Action While the precise mechanism of action of AQ-13 is not fully established, it is believed to function similarly to chloroquine. The drug likely kills malaria parasites by causing a buildup of toxic heme by inhibiting the enzyme that normally converts it to non-toxic hemozoin[4]. The outstanding attribute of AQ-13 is its ability to maintain activity against chloroquine-resistant P. falciparum strains[3][5]. ## Clinical Development AQ-13 has undergone clinical trials to evaluate its safety and efficacy: - A randomized, phase 2, non-inferiority clinical trial compared AQ-13 against artemether plus lumefantrine for treating uncomplicated P. falciparum malaria in Malian men[1][6]. - The trial enrolled 66 participants (33 in each group) between 2013 and 2015[1][6]. - No serious adverse events (grade 2-4) were reported, and asexual parasites were cleared by day 7 in both treatment groups[1][6]. - The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine, with cure rates of 100% for AQ-13 vs 93.9% for artemether plus lumefantrine[6]. - However, the intention-to-treat analysis did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures[6]. ## Safety Profile The most common side effects reported in clinical trials were: - Headache - Light-headedness - Dizziness - Gastrointestinal symptoms such as nausea[8] A total of 453 less-severe adverse events (≤grade 1) were reported across both treatment groups in the phase 2 trial: 214 in the artemether plus lumefantrine group and 239 in the AQ-13 group[1][6]. ## Potential Limitations Recent research has identified potential cross-resistance between AQ-13 and amodiaquine in Cambodian P. falciparum isolates, with a strong correlation coefficient of 0.8621 (P < 0.0001)[9]. This suggests that AQ-13 may face efficacy challenges in areas where amodiaquine resistance has developed[9]. ## Future Directions The most likely future application for AQ-13 would be as a partner drug in combination therapy for the management of uncomplicated falciparum malaria[3][5]. Further studies with more participants, including non-immune individuals, are needed to determine whether widespread use of modified 4-aminoquinolines like AQ-13 should be recommended[6].

Other names

7-chloro-N-[3-(diethylamino)propyl]quinolin-4-amine dihydrochloride