Anti-malarial activity of HCl salt of SKM13 (SKM13-2HCl)

Evaluation of the antimalarial activity of SAM13-2HCl with morpholine amide (SKM13 derivative) against antimalarial drug-resistant Plasmodium falciparum and Plasmodium berghei infected ICR mice

“…Nine new derivatives were synthesized (SAM09-2HCl to SAM17-2HCL) based on the previously published skeleton of SKM13-2HCl [ 7 ] ( Fig. 1 ).…”

“…We previously examined the antimalarial activities of the new derivatives in an animal model using the rodent P. berghei NK65 strain [ 6 ]. SAM13-2HCl exhibited a better SI value than SKM13-2HCl, and the relative difference between the 2 compounds was investigated in a rodent model using P. berghei (a CQ-susceptible strain) as previously described [ 7 ]. Accordingly, a 4-day suppression test was performed in mice using 10, 20, and 30 mg/kg of SAM13-2HC1 and SKM13-2HCl (single daily administration).…”

“…The blood stage of the P. falciparum 3D7 and K1 strains was propagated in 5% hematocrit of O+ human red blood cells suspended in optimal media [ 7 ]. Giemsa staining of methanol-fixed thin blood smears was used to monitor parasite growth [ 8 ].…”

“…Three mice were orally administered with the drug solution at 5 mg/kg in a single dose (100 μl/mouse); blood was then collected at different times, and the plasma obtained was stored at −80°C. The plasma concentration of each compound was plotted to generate a regression trend line to establish the kinetics of each compound using PK Solver 2.0 as previously described [ 7 , 12 ].…”

“…For parenteral products, increased solubility can help prevent precipitation at injection [ 10 ]. Therefore, to increase the solubility of SKM13, the salt form of SKM13 with HCl was developed; however, low plasma concentrations were detected, indicating poor efficiency attributed to limited intestinal adsorption [ 7 ]. This indicated that further research was required to counterbalance the hydrophobicity and hydrophilicity of SKM13 derivatives.…”