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 values were for the 13α-epimers _2I,4Br and _2I,4Cl (IC, 0.7 μM, 0.8 μM, respectively), both of which selectively inhibited the AKR1C1 isoform. The 13α-methyl-17-keto halogen derivatives _2Br and _4Cl were the most potent inhibitors of AKR1C2 (IC, 1.5 μM, 1.8 μM, respectively), with high selectivity for the AKR1C2 isoform. Compound _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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266253PMC
http://dx.doi.org/10.1080/14756366.2021.1937142DOI Listing

Publication Analysis

Top Keywords

oestrone halides
8
13α-methyl-17-keto halogen
8
halogen derivatives
8
potent inhibitors
8
inhibited akr1c1
8
synthesis evaluation
4
akr1c
4
evaluation akr1c
4
akr1c inhibitory
4
inhibitory properties
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!