Table-4.

In Vitro Antimalarial Activity and Cytotoxicity of 3,4-Disubstituted B-Ring Functionalized TAs (142–165)

				antimalarial activity (IC50 in nM)a
compd	R1	R2	R3	D6	Dd2	7G8	cytotoxicity (IC50 in nM)a HepG2	SIb (D6)	cLogPc
142	Et	Me	n-C4H9	883	680	260	ntd	-	2.0
143	Et	Me	n-C8H17	1166	633	244	nt	-	3.7
144	Et	Me		> 2500	2047	2500	nt	-	1.1
145	Et	Me		62	55	60	19200	310	2.7
146	Et	Me		56	60	75	18900	337	3.1
147	Et	Me		5.5	4.3	3.6	3300	600	2.6
148	Et	Me		> 2500	1576	855	nt	-	2.4
149	Et	Me		> 2500	> 2500	> 2500	nt	-	0.3
150	Me	Et		150	200	117	15800	105	2.7
151	Me	Et		111	201	128	23900	215	3.1
152	Me	Et		19	14	14	4500	237	2.6
153	Me	Me		60	38	47	21300	355	2.3
154	Me	Me		56	31	45	18100	323	2.7
155	Me	Me		2.4	1.7	1.5	6400	2667	2.2
156	Et	Et		54	30	88	16900	313	3.1
157	Et	Et		39	26	58	13000	333	3.6
158	Et	Et		1.6	1.0	2.5	3900	2437	3.0
159	–(CH2-CH2)2–			35	39	23	6200	177	2.6
160	–(CH2-CH2)2–			32	37	22	4600	144	3.1
161	–(CH2-CH2)2–			6.1	7.5	2.8	2700	442	2.5
162	Cl	Et	t-Bu	1217	> 2500	> 2500	nt	-	1.7
163	Cl	Et		> 2500	> 2500	> 2500	nt	-	2.4
164	Cl	Et		> 2500	> 2500	> 2500	nt	-	2.8
165	Cl	Et		2300	> 2500	2250	nt	-	2.3
CQ				13	115	130	nt	-	3.7
MQ				nt	nt	nt	21800	-	5.3

^aIC₅₀ values are the average of at least three determinations, each carried out in triplicate (± 10%). In order to compare results run on different days, and with different batches of each stain; CQ was run as a positive control. All results obtained were ‘normalized’ to the CQ values of 13 nM for D6, 115 nM for Dd2 and 130 nM for 7G8.

^bSI (selectivity index) = IC₅₀ (cytotoxicity)/IC₅₀ (D6)

^ccLogP values were calculated using ChemBioDraw Ultra software (version 14),

^dnt = not tested