Table 2. Cytotoxicity, Antiviral, and Anti-Integrase Activities of Derivatives 5a−i, 6a−i, 7a,b, and 8a,b.

					anti-IN activity, IC50a			antiviral activity
compd	R6	R7	R8	X	Mg2+ b	Mg2+ c	Mg2+ c	CC50d	EC50e	SIf
5a	H	H	H	C2H5	0.67	0.79, 0.44	135	99	34.8	2.8
5b	F	H	H	C2H5	0.58	0.23, 0.44	>333	>200	>50
5c	H	F	H	C2H5	1.3	1.2, 2.9	>333	>200	>50
5d	H	H	F	C2H5	26	5.2	>333	>200	>50
5e	Cl	H	H	C2H5	21	3.0	>333	ntg	ntg
5f	H	Cl	H	C2H5	14	3.6	>333	ntg	ntg
5g	H	H	Cl	C2H5	32	5.2	>333	>200	>50
5h	Cl	Cl	H	C2H5	3.9	1.8	135	72	>50
5i	H	Pyh	H	C2H5	2.3	2.7	110	>200	4.1	48.8
6a	H	H	H	H	0.040	0.06, 0.16	14	>200	1.17	>171
6b	F	H	H	H	0.030	0.14	2.3	>200	>50
6c	H	F	H	H	0.020	0.050	4.4	>200	>50
6d	H	H	F	H	0.018	0.16	16	>200	>50
6e	Cl	H	H	H	0.028	0.40	6.4	>200	46.1	4.3
6f	H	Cl	H	H	0.019	0.11	4.0	>200	>50
6g	H	H	Cl	H	0.023	0.51	44	>200	>50
6h	Cl	Cl	H	H	0.033	0.075	11, 34	156	3.2	62.5
6i	H	Pyh	H	H	0.028	0.18	14, 9.0	>200	0.17	>1176
7a	Cl	H		C2H5	3.3	2.1	120	ntg	ntg
7b	H	Cl		C2H5	>111	224	>333	ntg	ntg
8a	Cl	H		H	>111	56	166	ntg	ntg
8b	H	Cl		H	37	17	>333	ntg	ntg
1i					2.1
2i					0.05				1.0
3i					0.01				0.39j
4					0.016	0.017	0.44	>200	4.29	>47

^aInhibitory concentration 50% (μM) determined from dose response curves.

^bExperiments performed in duplicate using the high throughput electrochemiluminescent (HTECL) assay (ST assay in the presence of Mg²⁺).

^cExperiments performed in a gel-based assay in the presence of Mg²⁺ (see Figure 3).

^dCytotoxic concentration 50% (μM).

^eEffective concentration 50% (μM).

^fSelectivity index = CC₅₀/EC₅₀.

^gnt: not tested.

^hPy = 1-pyrrolidinyl.

ⁱLiterature data; see refs (9–11).

^jThis data is referred to EC₉₅.