Molecular Biology International

Research Article

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 numberaCAS numberbMolecular structureProduct nameTbIno1 Tm shiftc [°C]T. brucei Alamar Blue (% survival)dT. brucei ED50e (μM)HeLa Cells Alamar Blue (% survival)dHeLa ED50e(μM)
520331942-47-3389364.fig.0022-(2-furyl)benzoic acid4.29 ± 0.0735.4 ± 8.776.1 ± 6.073.0 ± 11.5>20 mM
186151155-53-2389364.fig.0032,3-Dihydrobenzo[b]furan-7-methanol4.09 ± 0.0933.8 ± 5.2370 ± 4086.5 ± 14.8
756947-94-0389364.fig.0042-methyl-3-furoic acid3.89 ± 0.0762.2 ± 10.663.3 ± 5.9
303857-25-8389364.fig.005(5-methyl-2-furyl)methanol3.79 ± 0.0845 ± 14.1023.3 ± 18.6
28488-93-7389364.fig.0063-furoic acid3.72 ± 0.0859.7 ± 5.548.2 ± 11.8
2721076-59-1389364.fig.0073-phenyl-4,5-dihydroisoxazol-5-one3.56 ± 0.0660.1 ± 21.089.4 ± 3.9
38317920-85-3389364.fig.008[4-(2-furyl)phenyl]methanol3.45 ± 0.0933.0 ± 7.2187 ± 1720 ± 10.6292 ± 31
51310333-68-3389364.fig.0092-(1H-pyrrol-1-yl)benzoic acid3.14 ± 0.09104.3 ± 9.698.5 ± 6.5
372143426-51-1389364.fig.010[4-(1H-pyrrol-1-yl)phenyl]methanol3.12 ± 0.0437.0 ± 14.0302 ± 1594.9 ± 19.43.3 ± 0.21 mM
4433305-08-7389364.fig.011methyl 1,3-thiazolane-2-carboxylate hydrochloride2.81 ± 0.186.7 ± 16.4108.2 ± 15.9
57774772-17-1389364.fig.0123-(1H-pyrrol-1-yl)thiophene-2-carboxylic acid2.78 ± 0.0832.2 ± 4.1>20 mM103.2 ± 2.8>20 mM
10316310-13-7389364.fig.0131,3-thiazolane-2-carboxylic acid2.63 ± 0.0877.9 ± 15.6103.3 ± 6.4
4784653-08-1389364.fig.0144-oxo-4-(2-thienyl)butanoic acid2.58 ± 0.05103.8 ± 13.1105.8 ± 9.3
60913735-12-1389364.fig.0156-chloro-3,4-dihydro-2H-1-benzothiin-4-one2.49 ± 0.0486.3 ± 6.674.5 ± 13.7
204699-83-2389364.fig.0161-(2,6-dihydroxyphenyl)ethan-1-one2.35 ± 0.0645.2 ± 9.736.3 ± 12.5
162700-06-1389364.fig.0171H-indol-3-ylmethanol2.31 ± 0.0632.5 ± 5.931.3 ± 1.416.3 ± 10.6103 ± 6
32839793-31-2389364.fig.0184H-thieno[3,2-b]pyrrole-5-carboxylic acid2.29 ± 0.1051.6 ± 13.3105.9 ± 6.9
2561780-17-2389364.fig.0192-quinolinylmethanol2.20 ± 0.0621.7 ± 6.040.1 ± 1.299.2 ± 19.5836 ± 68
12619785-39-8389364.fig.0202-(4-methyl-1,3-thiazol-2-yl)acetonitrile2.10 ± 0.0975.3 ± 15.469.7 ± 10.3
124533-31-3389364.fig.0211,3-benzodioxol-5-ol2.10 ± 0.0428.2 ± 7.139.7 ± 12.5
62056267-50-6389364.fig.022tert-butyl N-(2-thienyl)carbamate2.08 ± 0.140.1 ± 17.671.3 ± 13.6
2394651-97-2389364.fig.0232-amino-4-methylthiophene-3-carboxamide2.05 ± 0.0522.9 ± 7.063.0 ± 2.595.8 ± 9.3>20 mM
9959-48-3389364.fig.024indolin-2-one2.04 ± 0.0737.3 ± 9.2216 ± 1866.6 ± 18.7>2 mM
62629198-41-2389364.fig.0251,3-benzothiazol-2-ylmethylamine hydrochloride2.03 ± 0.0852.9 ± 13.995.1 ± 15.5
1631074-85-7389364.fig.0261H-indol-4-ylmethanol1.90 ± 0.0634.8 ± 0.85.2 ± 0.2 (mM)103.3 ± 8.72.5 ± 0.2 mM
201072-82-8389364.fig.0271-(1H-pyrrol-3-yl)ethan-1-one1.88 ± 0.0836.8 ± 9.73.6 ± 0.2 (mM)101.8 ± 4.3>5 mM
261300690-74-8389364.fig.0283-methylcinnolin-5-amine1.83 ± 0.1121.7 ± 8.5148 ± 862.5 ± 14.7726 ± 64
135129486-91-5389364.fig.0292-methyl-1H-imidazole-4-carbothioamide1.74 ± 0.09115.5 ± 16.690.3 ± 10.9
5983515-30-8389364.fig.0302,2 -bithien-5-ylmethanol1.72 ± 0.0655.3 ± 15.678 ± 11.6
91498-95-3389364.fig.0313-piperidinecarboxylic acid1.69 ± 0.1036.1 ± 11.076.6 ± 29.1
39187-51-4389364.fig.0322-(1H-indol-3-yl)acetic acid1.67 ± 0.0838.8 ± 10.142.6 ± 6.4
1326141-58-8389364.fig.033methyl 2-methyl-3-furoate1.64 ± 0.0934.3 ± 8.471.3 ± 11.3
3951677-46-9389364.fig.0344-hydroxy-1-methyl-1,2-dihydroquinolin-2-one1.62 ± 0.0354.3 ± 16.493.0 ± 0.3
522183210-33-5389364.fig.035(5-methyl-2-phenyl-3-furyl)methanol1.61 ± 0.0645.4 ± 7.924.3 ± 17.4
9726830-96-6389364.fig.0362-amino-4-methylbenzonitrile1.58 ± 0.0772.2 ± 14.481.4 ± 7.4
331121933-59-3389364.fig.037(4-methyl-4H-thieno[3,2-b]pyrrol-5-yl)methanol1.54 ± 0.0731.0 ± 7.1121 ± 1593.6 ± 14.9169 ± 10
29278348-24-0389364.fig.038indoline-2-carboxylic acid1.54 ± 0.1132.9 ± 9.337.6 ± 2.5
19039549-79-6389364.fig.0392-amino-4-methylbenzamide1.52 ± 0.0641.9 ± 11.046.7 ± 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 ( ).