. Author manuscript; available in PMC: 2010 Jun 15.

Published in final edited form as: Bioorg Med Chem Lett. 2009 May 3;19(12):3229–3232. doi: 10.1016/j.bmcl.2009.04.100

Table 1.

Effect of hybrid compounds 6, artemisinin (1), artelinic acid (15), dipeptidyl vinyl sulfones 5 and 12d and E64 on the inhibition of falcipain-2, chabaupain-1, and growth of P. falciparum W2 strain.

Compound	R¹	R²	R³	IC₅₀/μM		IC₅₀/nM
				FP-2^a	CP-1^b	W2 P. falciparum^a
Artemisinin	--	--	--	ND	ND	12.0±1.97
15	--	--	--	ND	ND	5.66±0.58
6a	CH₂Ph	H	Ph	16.5	56.8	4.09±0.13
6b	CH₂Ph	CH₂Ph	Ph	22.4	0.40	2.27±0.73
6c	CH₂CH₂Ph	CH₂Ph	Ph	9.22	0.538	3.94±0.28
6d	CH₂CH₂Ph	CH₂CHMe₂	Ph	4.95	2.29	2.08±0.89
6e	CH₂CH₂Ph	CH₂Ph	Me	21.6	ND	4.81±0.12
6f	CH₂CH₂Ph	CH₂CHMe₂	Me	0.35	ND	4.21±0.56
12d	CH₂CH₂Ph	CH₂CHMe₂	Ph	0.21	ND	>10000
5	CH₂CH₂Ph	CH₂CHMe₂	Ph	0.003^c	ND	22.0^d
E64	--	--	--	0.084	0.009	1955±121

Assays of falcipain inhibition and parasite development were determined as described earlier ¹⁵; assay of chabaupain inhibition was performed as described previously ²²;

non-recombinant falcipain ¹⁶;

Itg2 strain ¹⁶; ND, not determined.