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Prediction of the antibacterial activity of new chemical compounds is an important task, due to the growing problem of bacterial drug resistance. Generalized linear models (GLMs) were created using 85 amidrazone derivatives based on the results of antimicrobial activity tests, determined as the minimum inhibitory concentration (MIC) against Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Nocardia corallina, and Mycobacterium smegmatis. For the analysis of compounds characterized by experimentally measured MIC values, we included physicochemical properties (e.g., molecular weight, number of hydrogen donors and acceptors, topological polar surface area, compound percentages of carbon, nitrogen, and oxygen, melting points, and lipophilicity) as potential predictors. The presence of R1 and R2 substituents, as well as interactions between melting temperature and R1 or R2 substituents, were also considered. The set of potential predictors also included possible biological effects (e.g., antibacterial, antituberculotic) of tested compounds calculated with the PASS (Prediction of Activity Spectra for Substances) program. Using GLMs with least absolute shrinkage and selection (LASSO), least-angle regression, and stepwise selection, statistically significant models with the optimal value of the adjusted determination coefficient and of seven fit criteria were chosen, e.g., Akaike’s information criterion. The most often selected variables were as follows: molecular weight, PASS_antieczematic, PASS_anti-inflam, squared melting temperature, PASS_antitumor, and experimental lipophilicity. Additionally, relevant to the bacterial strain, the interactions between melting temperature and R1 or R2 substituents were selected, indicating that the relationship between MIC and melting temperature depends on the type of R1 or R2 substituent. Full article

Bacteria and fungi that are able to metabolize steroids express 3-ketosteroid-Δ¹-dehydrogenases (KstDs). KstDs such as AcmB form Sterolibacterium denitrificans Chol-1 catalyze the enantioselective 1α,2β-dehydrogenation of steroids to their desaturated analogues, e.g., the formation of 1,4-androstadiene-3,17-dione (ADD) from 4-androsten-3,17-dione (AD). The reaction catalyzed by KstD can be reversed if the appropriate electron donor, such as benzyl viologen radical cation, is present. Furthermore, KstDs can also catalyze transhydrogenation, which is the transfer of H atoms between 3-ketosteroids and 1-dehydrosteroids. In this paper, we showed that AcmB exhibits lower pH optima for hydrogenation and dehydrogenation by 3.5–4 pH units than those observed for KstD from Nocardia corallina. We confirmed the enantiospecificity of 1α,2β-hydrogenation and 1α,2β-transhydrogenation catalyzed by AcmB and showed that, under acidic pH conditions, deuterons are introduced not only at 2β but also at the 1α position. We observed a higher degree of H/D exchange at Y363, which activates the C2-H bond, compared to that at FAD, which is responsible for redox at the C1 position. Furthermore, for the first time, we observed the introduction of the third deuteron into the steroid core. This effect was explained through a combination of LC-MS experiments and QM:MM modelling, and we attribute it to a decrease in the enantioselectivity of C2-H activation upon the deuteration of the 2β position. The increase in the activation barrier resulting from isotopic substitution increases the chance of the formation of d³-substituted 3-ketosteroids. Finally, we demonstrate a method for the synthesis of 3-ketosteroids chirally deuterated at 1α,2β positions, obtaining 1α,2β-d²-4-androsten-3,17-dione with a 51% yield (8.61 mg). Full article

A novel application of whole cells of Nocardia corallina B-276 for the deracemisation of ibuprofen is reported. This microorganism successfully hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to ibuprofen, using a suspension of cells in a potassium phosphate buffer solution (0.1 M, pH = 7.0). These results can be explained by the presence of NHase and amidase enzymes, but the reactions are not enantioselective and low ee values were obtained. However, (R)-ibuprofen was isolated with >99% ee by a deracemisation process catalysed by N. corallina B-276. This is the first report of this kind of catalysis with this microorganism. Full article