Biotransformation of Chrysin to Baicalein: Selective C6-Hydroxylation of 5,7-Dihydroxyflavone Using Whole Yeast Cells Stably Expressing Human CYP1A1 Enzyme

© 2017 American Chemical Society. Naturally occurring polyphenolic compounds are of medicinal importance because of their unique antioxidant, anticancer, and chemopreventive properties. Baicalein, a naturally occurring polyhydroxy flavonoid possessing a diverse range of pharmacological activities, has been used in traditional medicines for treatment of various ailments. Apart from its isolation from natural sources, its synthesis has been reported via multistep chemical approaches. Here, we report a preparative-scale biotransformation, using whole yeast cells stably expressing human cytochrome P450 1A1 (CYP1A1) enzyme that allows regioselective C6-hydroxylation of 5,7-dihydroxyflavone (chrysin) to form 5,6,7-trihydroxyflavone (baicalein). Molecular modeling reveals why chrysin undergoes such specific hydroxylation mediated by CYP1A1. More than 92% reaction completion was obtained using a shake-flask based process that mimics fed-batch fermentation. Such highly efficient selective hydroxylation, using recombinant yeast cells, has not been reported earlier. Similar CYP-expressing yeast cell based systems are likely to have wider applications in the syntheses of medicinally important polyphenolic compounds

Aporphinoid Alkaloids Derivatives as Selective Cholinesterases Inhibitors: Biological Evaluation and Docking Study

Alzheimer's dementia is a neurodegenerative disease that affects the elderly population and causes memory impairment and cognitive deficit. Manifestation of this disease is associated to acetylcholine decrease; thus, Cholinesterase inhibition is the main therapeutic strategy for the treatment of Alzheimer's disease. In the present study, a series of aporphinoid alkaloids were tested as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors in vitro. Alkaloids liriodenine (3) and cassythicine (10) were the best inhibitors of both cholinesterases with IC50 values lower than 10 μM. In addition, these alkaloids demonstrated better inhibition of BChE than reference drug galantamine. In addition, some alkaloids showed selective inhibition. Laurotetatine clorhydrate (13) selectively inhibit AChE over BChE. On the contrary, pachyconfine (7) interacted more efficiently with BChE active site. Molecular modelling studies were performed in order to illustrate key interactions between most active compounds and the enzymes and to explain their selectivity. These studies reveal that the benzodioxole moiety exhibits strong interactions due to hydrogen bonds that form with the Glu201 (AChE) and Tyr440 (BChE) residues, which is reflected in the IC50 values.Fil: Cavallaro, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Murray, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Pungitore, Carlos Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Gutierrez, Lucas Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Phenotypic appearances of prostate utilizing PET-MRI and PET-CT with Ga-68-PSMA, radiolabelled choline and Ga-68-DOTATATE

The objective of this study was to highlight the role of multimodality imaging and present the differential diagnosis of abnormal tracer accumulation in the prostate and periprostatic tissue. Our departments have performed molecular imaging of the prostate utilizing PET-CT and PET-MRI with a range of biomarkers including F-FDG, radiolabelled choline, Ga-DOTATATE PET-CT and Ga-PSMA images. We retrospectively reviewed the varying appearances of the prostate gland in different diseases and incidental findings in periprostatic region. The differential diagnosis of pathologies related to prostate and periprostatic tissue on multimodality imaging includes malakoplakia, rhabdomyosarcoma, lymphoma, prostate cancer, neuroendocrine tumours, uchida changes, rectoprostatic fistula, synchronous malignancies, lymphocoele and schwanoma. There exists a wide differential for abnormal tracer accumulation in the prostate gland. As a radiologist and nuclear medicine physician, it is important to be aware of range of prostatic and periprostatic pathologies

Phenotypic appearances of prostate utilizing PET-MRI and PET-CT with 68Ga-PSMA, radiolabelled choline and 68Ga-DOTATATE.

The objective of this study was to highlight the role of multimodality imaging and present the differential diagnosis of abnormal tracer accumulation in the prostate and periprostatic tissue. Our departments have performed molecular imaging of the prostate utilizing PET-CT and PET-MRI with a range of biomarkers including F-FDG, radiolabelled choline, Ga-DOTATATE PET-CT and Ga-PSMA images. We retrospectively reviewed the varying appearances of the prostate gland in different diseases and incidental findings in periprostatic region. The differential diagnosis of pathologies related to prostate and periprostatic tissue on multimodality imaging includes malakoplakia, rhabdomyosarcoma, lymphoma, prostate cancer, neuroendocrine tumours, uchida changes, rectoprostatic fistula, synchronous malignancies, lymphocoele and schwanoma. There exists a wide differential for abnormal tracer accumulation in the prostate gland. As a radiologist and nuclear medicine physician, it is important to be aware of range of prostatic and periprostatic pathologies