Search for: [Abstract = "that compound C17 had also potent AKR1C3 inhibitory properties, which made him the second \(the first was ASP9521\) dual CBR1\-AKR1C3 inhibitor described in this thesis \(IC50 CBR1 = 0,68 μM\; IC50 AKR1C3 = 6,94 μM\). Based on combined analysis of both in silico and in vitro research, 1\-benzylpiperidine \(present in compounds P1\-P9\) was indicated as a favourable chemotype for further optimization research with intention to discovery of new dual enzymatic inhibitors. In vitro research, performed on A549 cell line, revealed that addition of compounds P18 and P25 increased anticancer activity of daunorubicin – the same effect was observed previously for ASP9521. The research described in this doctoral thesis led to optimized three\-dimensional models of selected CBR1 and AKR1C3 crystal structures. The models were applied to identify new inhibitors of main ANT reductases, including compounds with a new, unique dual CBR1\-AKR1C3 inhibitory properties. The compound selection was based not only on poses achieved in prospective screenings, but also on evaluation of selected ADMET parameters, predicted by dedicated software, in accordance with rules of modern, rational drug design. Both the best compounds from C series \(C2, C17\) and P series \(P18, P25, P27\) did not contain structural features that could enhance a risk of toxicity or cause unfavourable pharmacokinetic"]

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