Design and Synthesis of WM5 Analogues as HIV-1 TAR RNA Binders

Table 1: Anti-HIV-1 activity and cytotoxicity of quinolones in MT-4 cells and inhibition of Tat-TAR complex formation.

Compd	EC₅₀ (µM)^a,c HIV-1 (III_B)	CC₅₀ (µM)^b,c	SI^d	Ki Tat-TAR (µM)^e
1	>296	>296	1	N.T. ^f
2	>363	363	1	N.T.
3	>34.9	34.9 ± 1.43	<1	N.T.
4	>19.8	19.8 ± 5.02	<1	N.T.
5^g	5.05 ± 0.41	20.9 ± 3.93	4	1.15 ± 0.55
6	1.21 ± 0.08	5.92 ± 2.19	5	0.91 ± 0.27
7	≥3.42	3.94 ± 0.62	≤1	2.18 ± 0.40
8	70.8 ± 0.71	>254	>4	N.T.
9^g	1.16 ± 0.18	3.97 ± 0.70	3	N.D.^h
10^g	≥0.18	3.34 ± 1.47	≤18	1.72 ± 0.22
11	3.37 ± 1.62	11.65 ± 1.17	3.5	N.D.
12	≥0.67	10.70± 7.76	≤16	N.D.
WM5ⁱ	0.15 ± 0.05	2.21 ± 1.05	15	2.22 ± 0.66

^a EC₅₀: concentration of compound required to achieve 50% protection of MT-4 cells from HIV-1 induced cytopathogenicity, as determined by the MTT method. ^b CC₅₀: concentration of compound that reduces the viability of mock-infected cells by 50%, as determined by the MTT method. ^c All data represent mean values ± standard deviations for three separate experiments. ^d SI: ratio of CC₅₀/EC₅₀. ^e Ki from FQA experiments performed with 10 aa FAM–Tat peptide in Tris 10 mM, pH 7.5, Mg(ClO₄)₂ 1 mM, NaCl 20 mM (TNMg), 0.01% Triton X-100. ^f N.T.: not tested. ^g Reference [²⁵]. ^h N.D.: not determined due to solubility issue. ⁱ Reference [²⁰].