5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents
Link: https://www.mdpi.com/1420-3049/26/13/3991/htm
Title: 5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents
Authors: Somruedee Jansongsaeng, Nitipol Srimongkolpithak, Jutharat Pengon , Sumalee Kamchonwongpaisan, Tanatorn Khotavivattana
Abstract:
The rapid emergence of drug resistance to the current antimalarial agents has led to the urgent need for the discovery of new and effective compounds. In this work, a series of 5-phenoxy primaquine analogs with 8-aminoquinoline core (7a–7h) was synthesized and investigated for their antimalarial activity against Plasmodium falciparum. Most analogs showed improved blood antimalarial activity compared to the original primaquine. To further explore a drug hybrid strategy, a conjugate compound between tetraoxane and the representative 5-phenoxy-primaquine analog 7a was synthesized. In our work, the hybrid compound 12 exhibited almost a 30-fold increase in the blood antimalarial activity (IC50 = 0.38 ± 0.11 μM) compared to that of primaquine, with relatively low toxicity against mammalian cells (SI = 45.61). Furthermore, we found that these 5-phenoxy primaquine analogs and the hybrid exhibit significant heme polymerization inhibition, an activity similar to that of chloroquine, which could contribute to their improved antimalarial activity. The 5-phenoxy primaquine analogs and the tetraoxane hybrid could serve as promising candidates for the further development of antimalarial agents.
Cite this:
Jansongsaeng, S.; Srimongkolpithak, N.; Pengon, J.; Kamchonwongpaisan, S.; Khotavivattana, T. 5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents, Molecules 2021, 26, 3991.
