Abstract：
:In the present study, we have investigated the inhibition of thermolysin and pseudolysin by a series of compounds previously identified as matrix metalloproteinase (MMP) inhibitors using experimental binding studies and theoretical calculations. The experimental studies showed that some of the compounds were able to inhibit thermolysin and pseudolysin in the low μM range. The studies revealed that, in general, the compounds bound in the order MMPs > pseudolysin > thermolysin, and the strongest pseudolysin and thermolysin binders were compounds 8-12. Furthermore, compounds 8 and 9 were unique in that they bound much stronger to the two bacterial enzymes than to the MMPs. The docking calculations suggested that the phenyl group of the strongest binders (compounds 8 and 9) occupy the S2(')-subpocket, while a second ring system occupy the S1-subpocket in both thermolysin and pseudolysin. When the compounds possess two ring systems, the largest and most electron rich ring system seems to occupy the S1-subpocket.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Adekoya OA,Sjøli S,Wuxiuer Y,Bilto I,Marques SM,Santos MA,Nuti E,Cercignani G,Rossello A,Winberg JO,Sylte Idoi
10.1016/j.ejmech.2014.10.009subject
Has Abstractpub_date
2015-01-07 00:00:00pages
340-8eissn
0223-5234issn
1768-3254pii
S0223-5234(14)00935-0journal_volume
89pub_type
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