Aldo-keto reductases type 1C (AKR1C), members of the aldo-keto reductase superfamily, are involved in the metabolism of steroid hormones, neurosteroids, and prostaglandins and contribute to chemoresistance, by either metabolizing chemotherapeutic agents or indirectly by eradicating the cellular stress caused by chemotherapeutics. These enzymes represent interesting drug targets for chemoresistant cancers. High-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer and the leading cause of death out of all gynecological cancers. The aim of our master thesis was to investigate 11 compounds as inhibitors of aldo-keto reductase 1C (AKR1C) enzymes and their effects on proliferation of control and ovarian cancer cell lines (HGSOC). Six of the 11 compounds can be classified as estrane derivatives (AD-4, AD-5, DTP-036, DTP-026, DTP-150, DTP-150-KK), and the other 5 are tetrahydronaphtalen-1-one derivatives (DTP-153, DTP-154, DTP-155, DTP-158, AD-13). The inhibitory properties towards AKR1C1–C3 enzymes were measured at inhibitor concentrations of 10 and 100 µM with spectrophotometric detection of oxidation of the substrate 1-acenaphthenol in the presence of NAD + as coenzyme. The effect of inhibitors on cell viability was determined with Alamar Blue assay. The control ovarian cell line (HIO-80) and HGSOC cell lines (COV362 and OVSAHO) were exposed to 11 synthetic inhibitors at different concentrations (10 µM and 50 µM) for 48 hours. 13α-estrone derivatives were more effective inhibitors than tetrahydronaphtalen-1-one derivates. The two most active inhibitors of the AKR1C2 isoenzyme, DTP-036 and AD-4, had an IC50 value of 3.3 µM and 14.2 µM, respectively. At 100 µM concentration two of tetrahydronaphtalen-1-one derivates (DTP-154 in DTP-158) also showed more than 50% inhibition of AKR1C3. We also predicted the binding of AD-4 and DTP-036 into the binding pocket of AKR1C2 by using AutoDock Vina. The lower IC$_50$ value for DTP-036 correlates with the higher number of predicted hydrophobic interactions between DTP-036 and AKR1C2. Cell viability of the OVSAHO cells was significantly decreased when exposed to 50 µM DTP-153, DTP-155, AD -13, and DTP-150. There were no effects on control cell line HIO-80 and HGSOC cell line COV362. To conclude, we discovered new selective inhibitors of AKR1C2 isoform and four compounds that decrease viability of the HGSOC cell line OVSAHO
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