20.500.12556/RUL-144791 Synthesis and evaluation of AKR1C inhibitory properties of A-ring halogenated oestrone derivatives Enzymes AKR1C regulate the action of oestrogens, androgens, and progesterone at the pre-receptor level and are also associated with chemo-resistance. The activities of these oestrone halides were investigated on recombinant AKR1C enzymes. The oestrone halides with halogen atoms at both C-2 and C-4 positions (13β-, 13α-methyl-17-keto halogen derivatives) were the most potent inhibitors of AKR1C1. The lowest IC$_{50}$ values were for the 13α-epimers 2_2I,4Br and 2_2I,4Cl (IC$_{50}$, 0.7 μM, 0.8 μM, respectively), both of which selectively inhibited the AKR1C1 isoform. The 13α-methyl-17-keto halogen derivatives 2_2Br and 2_4Cl were the most potent inhibitors of AKR1C2 (IC$_{50}$, 1.5 μM, 1.8 μM, respectively), with high selectivity for the AKR1C2 isoform. Compound 1_2Cl,4Cl showed the best AKR1C3 inhibition, and it also inhibited AKR1C1 (Ki: AKR1C1, 0.69 μM; AKR1C3, 1.43 μM). These data show that halogenated derivatives of oestrone represent a new class of potent and selective AKR1C inhibitors as lead compounds for further optimisations. aldo-keto reductases inhibition halogenated oestrone derivatives structure–activity relationships aldo-keto reduktaze halogenirani derivati estrona zaviranje true false true Angleški jezik Slovenski jezik Članek v reviji 2023-03-13 10:09:29 2023-03-13 10:09:33 2023-03-14 03:29:55 0000-00-00 00:00:00 2021 0 0 Str. 1499–1507 no. 1 Vol. 36 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006 1475-6366 10.1080/14756366.2021.1937142 67617027 Synthesis_and_evaluation_of_AKR1C_inhibitory_properties_.pdf Synthesis_and_evaluation_of_AKR1C_inhibitory_properties_.pdf 1 E7CF8F257893B62A5E5E898726A7C486 11cea34de025a04e53cd3a30368a2a65ac3bad2f0faac57b242f73ed0e3e8efd e98fae79-c17e-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167304 https://www.tandfonline.com/doi/full/10.1080/14756366.2021.1937142 0 ce304921-c17e-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167303 Medicinska fakulteta 0 0 0