China
Africa
Explore chapters and articles related to this topic
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Published in Sheryl S. Smith, Neurosteroid Effects in the Central Nervous System, 2003
M., Palackal, N., and Ratnam, K., Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones, Biochem. J., 351 (Pt. 1), 67-77, 2000. Deyashiki, Y., Ogasawara, A., Nakayama, T., Nakanishi, M., Miyabe, Y., Sato, K., and Hara, A., Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihγ-drodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder, Biochem. J., 299 (Pt. 2), 545-552, 1994.Hara, A., Matsuura, K., Tamada, Y., Sato, K., Miyabe, Y., Deyashiki, Y., and Ishida, N., Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells, Biochem. J., 313 (Pt.
Anti-Cancer Agents from Natural Sources
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Felipe Gonzalez
Flavones contain 2-phenylchromen-4-one backbone with an oxyhetero-cyclic enone system in their structure. These are sometimes derived from flavanones and are commonly found in spices, purple/red color vegetables and fruits, occasionally in 7-O-glycosidic form. Flavones protect the plants from harmful UV radiation and some flavones possess anti-inflammatory, antiviral, and antineoplastic activities. A common example of an anticancer flavone is chrysin. Chrysin (5,7-dihydroxyflavone) is isolated from the blue crown passionflower (Figure 5.17). According to Walle et al., chrysin contains a low bioavailability (Walle et al., 2001) and is quickly excreted (Nabavi et al., 2015). Regardless of its low bioavail-ability, research has been conducted to determine chrysin’s effect on cancerous cell lines. Bahadori et al. (2016) conducted a study to evaluate the antineoplastic efficiency of chrysin in CT-26 (colon cancer) cells, both in vitro and animal models. The CT-26 cells were subjected to diverse concentrations of chrysin and up to 50% cellular growth inhibition was observed, compared to untreated cells. Furthermore, chrysin’s cytotoxic properties adopted apoptosis in vivo. Khoo et al. (2010) carried out in vitro antineoplastic activity of chrysin in human cervical cancer, breast carcinoma, prostate cancer, esophageal squamous carcinoma, malignant glioma, and leukemia cells. Zhang et al. (2004) reported chrysin-induced prevention of cellular growth through adaptation of apoptosis in HeLa cells. The study also revealed subsequent drepressionof the proliferating cell nuclear antigen (PCNA) caused by chrysin. Further research conducted on HeLa cells by Brandenstein et al., (2008) reportedthat chrysin could induce p38 and NFkappaB/65 activation. In malignant glioma (U87-MG), prostate, and breast malignant cells chrysin could inhibit proliferation and induced apoptosis (Nabavi et al., 2015). In addition, chrysin was capable to synergize the competence of wogonin to treat patients suffering from overe xpression in AKR1C1/1C2 induced by IL-6 in NSCLC (Wang et al., 2007). The same research also reported that chrysin disrupted G2/M phase in SW480 cells.
Synthesis and evaluation of AKR1C inhibitory properties of A-ring halogenated oestrone derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Maša Sinreih, Rebeka Jójárt, Zoltán Kele, Tomaž Büdefeld, Gábor Paragi, Erzsébet Mernyák, Tea Lanišnik Rižner
The AKR1C1-3 recombinant enzymes were prepared as described previously28. The in vitro catalytic activities of AKR1C1–3 were determined spectrophotometrically by measuring increased NADH absorbance (ελ340=6220 M−1 cm−1) in the presence of the chiral artificial substrate 1-acenaphthenol. The enzymatic reactions (300 µL) were performed in 0.09 M potassium phosphate buffer (pH 9.0), 0.005% (v/v) Triton X-114, 0.05% (v/v) DMSO, 2.3 mM NAD+, and 1-acenaphthenol (all Sigma). The final substrate concentrations (i.e. 1-acenaphthenol) were 90 µM, 180 µM, and 250 µM, for AKR1C1, AKR1C2, and AKR1C3, respectively. Five microlitres of each tested compound in DMSO was added to the reaction mixture, with the reactions started by addition of the enzymes, at 0.1 µM, 0.3 µM, and 1.5 µM for AKR1C1, AKR1C2, and AKR1C3, respectively. The measurements were performed in duplicate and were repeated as two independent experiments, using a microplate reader (PowerWave XS; Biotek, Winooski, VT). The initial velocities were calculated and the IC50 values were determined from the plots of residual activity (RA) versus log10 (inhibitor concentration), using GraphPad Prism, version 7.00 (GraphPad Software, Inc., San Diego, CA). Type of inhibition, KM, KI, and α were determined using either GraphPad Prism, version 7.00 (GraphPad Software, Inc., San Diego, CA) or SigmaPlot, version 14.0 (Systat Software, Inc., San Jose, CA).
The possible role of methylglyoxal metabolism in cancer
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Khalid O. Alfarouk, Saad S. Alqahtani, Saeed Alshahrani, Jakob Morgenstern, Claudiu T. Supuran, Stephan J. Reshkin
For AKR inhibitors, the Pharmacodiagnostics approach should be implemented for the rational use of selection for example, forAKR1B1 is inhibited by epalrestat94AKR1C1 is inhibited by 3-bromo-5-phenylsalicylic acid95.AKR1C3 is inhibited by cinnamic acid96,97.