Synthesis and antimalarial activity of urenyl Bis-chalcone in vitro and in vivo

Figures & data

Scheme 1.  Synthesis of Bis-chalcone 4–17. 1) Me2CO, 3–7 h; 2) NaOH, MeOH, 3–5 h.; 3) R-PhCHO. R=; 4) 2″,4″-OMe; 5) 3″,4″,5″-OMe; 6) 2″,5″-OMe; 7) 3″,4″-Cl2; 8) 3″,4″-OMe; 9) 2″,4″,6″-OMe; 10) 2″,4″,5″-OMe; 11) H; 12) 4″-F; 13) 2″,3″-F; 14) 4″-Cl; 15) 4″-OMe; 16) 3″,4″-OCH2O; 17) 4″-Me.

Table 1.  Percentage of inhibition of heme polymerization and FACS.

Compound	% inhibition of heme formation^a	IC50 (mM)^b	FACS µM (IC50)^c
4	<5	–	0.78
5	87.05 ± 0.77*	4.12	0.69
6	<5	–	0.78
7	29.79 ± 8.32	–	>10
8	58.53 ± 2.49	12.05	3.06
9	<5	–	0.78
10	<5	–	0.36
11	<5	–	5.39
12	<5	–	0.78
13	<5	–	0.68
14	<5	–	4.19
15	<5	–	8.30
16	25.64 ± 0.82	–	2.45
17	<5	–	>10
Chloroquine	88.03 ± 0.77	1.33	–

The results are shown by the media ± SEM. 1–16 are the compounds tested.

^aPercentage of inhibition.

^bIC₅₀ of β-hematin formation. The results are expressed by the media ± SEM.

^cIC₅₀ values (µM) for tested compounds as determined by flow cytometry as inhibitors of cultured Plasmodium falciparum parasites.

*p > 0.05 compared with chloroquine.

Figure 1.  Effects on globin hydrolysis of chalcone derivate. The samples were solubilized in SDS-sample buffer containing β-mercapto ethanol and boiled before electrophoresis in 15% SDS-PAGE gels. The gels were stained with Coomassie blue. The position of MW standard is shown in kDa. Undergraded globin appears at 14 kDa. A, control human hemoglobin; B, control hemoglobin, without enzyme; C, control, enzyme with hemoglobin; 5, compound (100 mM); MW, molecular weight; LEP, leupeptin (100 mM); PEP, pepstatin (100 mM).

Figure 2.  Percentage of inhibition of hemoglobin hydrolysis. The results are expressed by the media ± SEM. Compound 5 compared with LEP and PEP. *p < 0.01 compared with LEP. LEP, leupeptin; PEP, pepstatin.

Figure 3.  Percentage of parasitemias at 4th day postinfection (compound 5 [20 mg/kg] and CQ [25 mg/kg]). *p < 0.05, compared with saline treated-mice and chloroquine (n = 5).