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[摘要]：In the present work, 22 compds. of the U.S. NCI compd. library (size 273K) were identified as putative thermolysin binders by structure based virtual screening with the ICM software (ICM-VLS). In vitro competitive binding assays confirmed that 12 were thermolysin binders. Thermolysin binding modes of the 12 compds. were studied by docking using ICM and Molegro Virtual Docker (MVD). The most potent inhibitor had an IC50 value of 6.4 ?10-8 mM (NSC250686, 1b-D-arabinofuranosyl-N4-lauroylcytosine). The structure of this compd. is quite different from the other 11 compds. Nine out of the 12 compds. contained a similar chem. skeleton (3-nitrobenzamide derivs.) and have IC50 values ranging from 697.48 to 0.047 mM. The ICM-VLS score and the activity profiles (pIC50 values) were compared and found to be somewhat linearly correlated (R2 = 0.78). Kinetic studies showed that, except for NSC285166 (oxyquinoline), the compds. are competitive thermolysin inhibitors. |
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