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. 2020 Mar 12;25(6):1305. doi: 10.3390/molecules25061305

Table 1.

The inhibitory potencies of selected psoralen derivatives against the Mtb proteasome. Inhibition data for IP is added to evaluate selectivity profile of compounds.

Compound Chemical Structure IC50 (µM) and (Hill Coefficient) Ki and Type of Inhibition a RA b at 10 µM (%) or Ki or IC50 (µM) against ß5i of IP (refs [41,42])
Bortezomib graphic file with name molecules-25-01305-i001.jpg 0.11 ± 0.03
(0.76)		 Ki = 133 ± 5 nM
Mixed inhibition (R2 = 0.94, α = 0.85)
(Slow) reversible inhibition		 IC50 = 0.004 µM (ref [35])
PR-957 graphic file with name molecules-25-01305-i002.jpg 2.2 ± 1.0
(0.91)		 kinact/Ki = 96 ± 41 M−1·s−1
Ki = 5.2 ± 1.9 µM
Noncompetitive inhibition (R2 = 0.83)
Irreversible inhibition		 IC50 = 0.015 ± 0.002 µM
(ref [41])
1 graphic file with name molecules-25-01305-i003.jpg 39 ± 7
(0.69)		 ND Ki = 137 ± 33 µM
2 graphic file with name molecules-25-01305-i004.jpg 15 ± 2
(1.75)		 ND 83%
3 graphic file with name molecules-25-01305-i005.jpg 31 ± 5
(1.22)		 ND 53%
4 graphic file with name molecules-25-01305-i006.jpg 4 ± 3
(1.59)		 ND Ki = 12.7 ± 3.7 µM
5 graphic file with name molecules-25-01305-i007.jpg 17 ± 3
(0.70)		 ND 93%
6 graphic file with name molecules-25-01305-i008.jpg 2.2 ± 0.3
(0.70)		 ND 82%
7 graphic file with name molecules-25-01305-i009.jpg 8 ± 5
(0.42)		 ND 100%
8 graphic file with name molecules-25-01305-i010.jpg 3.7 ± 1.5
(1.05)		 Ki = 5.6 ± 20.8 µM
Mixed inhibition (R2 = 0.54, α = 0.19)
Reversible inhibition		 100%
9 graphic file with name molecules-25-01305-i011.jpg 2 ± 2
(2.27)		 ND 66%
10 graphic file with name molecules-25-01305-i012.jpg 3 ± 2
(4.46)		 ND 100%
11 graphic file with name molecules-25-01305-i013.jpg 8.8 ± 1.0
(0.90)		 Ki = 4.2 ± 2.1 µM
Mixed inhibition (R2 = 0.91, α = 6.67)
(Partially) reversible inhibition		 IC50 = 0.94 ± 1.1 µM
12 graphic file with name molecules-25-01305-i014.jpg 5 ± 2
(1.05)		 ND IC50 = 1.8 ± 0.4 µM
13 graphic file with name molecules-25-01305-i015.jpg 3.2 ± 0.3
(0.90)		 Ki = 1.1 ± 0.9 µM
Mixed inhibition (R2 = 0.52, α = 6.94 × 10^16)
(Partially) reversible inhibition		 IC50 = 4.4 ± 0.1 µM
14 graphic file with name molecules-25-01305-i016.jpg 9 ± 5
(2.42)		 ND IC50 = 6.9 ± 2.1 µM
15 graphic file with name molecules-25-01305-i017.jpg 5.8 ± 2.1
(0.55)		 Ki = 14.9 ± 45.0 µM
Mixed inhibition (R2 = 0.77, α = 0.22)
Reversible inhibition		 ND

aKi determined with GraphPad Prism by fitting the data to several inhibition models (mixed, competitive, noncompetitive, uncompetitive). The best scoring model was further examined by creating Dixon, Lineweaver-Burk and Michaelis-Menten plots. Km for Suc-LLVY-AMC is 60 ± 15 µM (see Supplementary data for details). ND, not determined. b The data were calculated as residual activities (RAs) of β5i in the presence of 10 μM of each compound (standard errors for RAs were < 15%).