Screening the MayBridge Rule of 3 Fragment Library for Compounds That Interact with the Trypanosoma brucei myo-Inositol-3-Phosphate Synthase and/or Show Trypanocidal Activity
Table 1
Screening the MayBridge Rule of 3 Fragment Library for TbINO1 differential scanning fluorimetry hits with a °C.
Library numbera
CAS numberb
Molecular structure
Product name
TbIno1 Tm shiftc [°C]
T. brucei Alamar Blue (% survival)d
T. brucei ED50e (μM)
HeLa Cells Alamar Blue (% survival)d
HeLa ED50e(μM)
520
331942-47-3
2-(2-furyl)benzoic acid
4.29 ± 0.07
35.4 ± 8.7
76.1 ± 6.0
73.0 ± 11.5
>20 mM
186
151155-53-2
2,3-Dihydrobenzo[b]furan-7-methanol
4.09 ± 0.09
33.8 ± 5.2
370 ± 40
86.5 ± 14.8
75
6947-94-0
2-methyl-3-furoic acid
3.89 ± 0.07
62.2 ± 10.6
63.3 ± 5.9
30
3857-25-8
(5-methyl-2-furyl)methanol
3.79 ± 0.08
45 ± 14.10
23.3 ± 18.6
28
488-93-7
3-furoic acid
3.72 ± 0.08
59.7 ± 5.5
48.2 ± 11.8
272
1076-59-1
3-phenyl-4,5-dihydroisoxazol-5-one
3.56 ± 0.06
60.1 ± 21.0
89.4 ± 3.9
383
17920-85-3
[4-(2-furyl)phenyl]methanol
3.45 ± 0.09
33.0 ± 7.2
187 ± 17
20 ± 10.6
292 ± 31
513
10333-68-3
2-(1H-pyrrol-1-yl)benzoic acid
3.14 ± 0.09
104.3 ± 9.6
98.5 ± 6.5
372
143426-51-1
[4-(1H-pyrrol-1-yl)phenyl]methanol
3.12 ± 0.04
37.0 ± 14.0
302 ± 15
94.9 ± 19.4
3.3 ± 0.21 mM
44
33305-08-7
methyl 1,3-thiazolane-2-carboxylate hydrochloride
2.81 ± 0.1
86.7 ± 16.4
108.2 ± 15.9
577
74772-17-1
3-(1H-pyrrol-1-yl)thiophene-2-carboxylic acid
2.78 ± 0.08
32.2 ± 4.1
>20 mM
103.2 ± 2.8
>20 mM
103
16310-13-7
1,3-thiazolane-2-carboxylic acid
2.63 ± 0.08
77.9 ± 15.6
103.3 ± 6.4
478
4653-08-1
4-oxo-4-(2-thienyl)butanoic acid
2.58 ± 0.05
103.8 ± 13.1
105.8 ± 9.3
609
13735-12-1
6-chloro-3,4-dihydro-2H-1-benzothiin-4-one
2.49 ± 0.04
86.3 ± 6.6
74.5 ± 13.7
204
699-83-2
1-(2,6-dihydroxyphenyl)ethan-1-one
2.35 ± 0.06
45.2 ± 9.7
36.3 ± 12.5
162
700-06-1
1H-indol-3-ylmethanol
2.31 ± 0.06
32.5 ± 5.9
31.3 ± 1.4
16.3 ± 10.6
103 ± 6
328
39793-31-2
4H-thieno[3,2-b]pyrrole-5-carboxylic acid
2.29 ± 0.10
51.6 ± 13.3
105.9 ± 6.9
256
1780-17-2
2-quinolinylmethanol
2.20 ± 0.06
21.7 ± 6.0
40.1 ± 1.2
99.2 ± 19.5
836 ± 68
126
19785-39-8
2-(4-methyl-1,3-thiazol-2-yl)acetonitrile
2.10 ± 0.09
75.3 ± 15.4
69.7 ± 10.3
124
533-31-3
1,3-benzodioxol-5-ol
2.10 ± 0.04
28.2 ± 7.1
39.7 ± 12.5
620
56267-50-6
tert-butyl N-(2-thienyl)carbamate
2.08 ± 0.1
40.1 ± 17.6
71.3 ± 13.6
239
4651-97-2
2-amino-4-methylthiophene-3-carboxamide
2.05 ± 0.05
22.9 ± 7.0
63.0 ± 2.5
95.8 ± 9.3
>20 mM
99
59-48-3
indolin-2-one
2.04 ± 0.07
37.3 ± 9.2
216 ± 18
66.6 ± 18.7
>2 mM
626
29198-41-2
1,3-benzothiazol-2-ylmethylamine hydrochloride
2.03 ± 0.08
52.9 ± 13.9
95.1 ± 15.5
163
1074-85-7
1H-indol-4-ylmethanol
1.90 ± 0.06
34.8 ± 0.8
5.2 ± 0.2 (mM)
103.3 ± 8.7
2.5 ± 0.2 mM
20
1072-82-8
1-(1H-pyrrol-3-yl)ethan-1-one
1.88 ± 0.08
36.8 ± 9.7
3.6 ± 0.2 (mM)
101.8 ± 4.3
>5 mM
261
300690-74-8
3-methylcinnolin-5-amine
1.83 ± 0.11
21.7 ± 8.5
148 ± 8
62.5 ± 14.7
726 ± 64
135
129486-91-5
2-methyl-1H-imidazole-4-carbothioamide
1.74 ± 0.09
115.5 ± 16.6
90.3 ± 10.9
598
3515-30-8
2,2-bithien-5-ylmethanol
1.72 ± 0.06
55.3 ± 15.6
78 ± 11.6
91
498-95-3
3-piperidinecarboxylic acid
1.69 ± 0.10
36.1 ± 11.0
76.6 ± 29.1
391
87-51-4
2-(1H-indol-3-yl)acetic acid
1.67 ± 0.08
38.8 ± 10.1
42.6 ± 6.4
132
6141-58-8
methyl 2-methyl-3-furoate
1.64 ± 0.09
34.3 ± 8.4
71.3 ± 11.3
395
1677-46-9
4-hydroxy-1-methyl-1,2-dihydroquinolin-2-one
1.62 ± 0.03
54.3 ± 16.4
93.0 ± 0.3
522
183210-33-5
(5-methyl-2-phenyl-3-furyl)methanol
1.61 ± 0.06
45.4 ± 7.9
24.3 ± 17.4
97
26830-96-6
2-amino-4-methylbenzonitrile
1.58 ± 0.07
72.2 ± 14.4
81.4 ± 7.4
331
121933-59-3
(4-methyl-4H-thieno[3,2-b]pyrrol-5-yl)methanol
1.54 ± 0.07
31.0 ± 7.1
121 ± 15
93.6 ± 14.9
169 ± 10
292
78348-24-0
indoline-2-carboxylic acid
1.54 ± 0.11
32.9 ± 9.3
37.6 ± 2.5
190
39549-79-6
2-amino-4-methylbenzamide
1.52 ± 0.06
41.9 ± 11.0
46.7 ± 23.7
aArbitrary Library number.
bCAS numbers are unique identifiers assigned by the “Chemical Abstracts Service” to describe every chemical described in the open access scientific literature.
cTm shift in °C, observed for TbINO1 in the presence of compound (1 mM) and value is mean ± SD from the Boltzman curve fitting; see Section 2 for details, mean ± SD ().
dFor cytotoxicity studies, see Section 2 for details and values are percentage of controls in the absence of compound, either mean ± SD () or mean ± SE (), the latter being in bold.
eFor trypanocidal and cytotoxicity activity, see Section 2 for details and values are ED50s ± SD ().