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In Silico Approach to Cancer Therapy
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
In a study, the use of the EMCIT approach was done in the case of pancreatic cancer. To identify an EMCIT-suitable hydrolase, they have recognized five phosphatases and one extracellular sulfatase (SULF1), considered an excellent target for EMCIT. SULF1 is known for its specific endoglucosamine-6-sulfatase and (Morimoto-Tomita et al., 2002) arylsulfatase activity, due to causing desulfurization from the aromatic phenyl ring. Therefore, arylsulfatase activity might be linked to arylphosphatase action that is known for alkaline phosphatase (ALP) and prostatic acid phosphatase (PAP) activity for hydrolysis of IQ2–P (ammonium 2-(2′-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone) (Ho et al., 2002; Chen et al., 2006; Pospisil et al., 2007; Wang et al., 2007; Kassis et al., 2008). IQ2–P was modified to IQ2–S (2-(2′-sulfooxyphenyl)-6-iodo-4-(3H)-quinazolinone), a sulphate-based analog. This IQ2–S was docked into the neighboring homologous 3-D configuration of SULF1, arylsulfatase A (ARSA). A docking study of IQ2–S and IQ2–P with ARSA, ALP, and PAP revealed that these three enzymes of an alkaline-phosphatase family can bind para-nitrophenyl sulfates or phosphates, exhibiting sulfatidic and phosphatidic actions (O’Brien and Herschlag, 1999; Catrina et al., 2007). Overall, the docking study predicts that the replacement of phosphate with sulfate on an iodoquinazolinone skeleton would shift this EMCIT concept to sulfatases from phosphatases, leading to a new prodrug target scheme generation. Particularly in the case of pancreatic cancer, IQ2–S (sulfate derived prodrug), has been proven as a potential prodrug for ARSA and later its neighboring analog SULF1.
Short-term metabolic disruptions in urine of mouse models following exposure to low doses of oxygen ion radiation
Published in Journal of Environmental Science and Health, Part C, 2021
Michael Girgis, Yaoxiang Li, Meth Jayatilake, Kirandeep Gill, Sirao Wang, Kepher Makambi, Vijayalakshmi Sridharan, Amrita K Cheema
Moreover, we observed downregulation of N- Acetyl glucosamine-6-sulfate in mice exposed to lower doses of oxygen radiation; this metabolite is a physiological intermediate generated during the degradation of keratan sulfate and usually hydrolyzed intralysosomally by N-acetylglucosamine-6-sulfate sulfatase. A decrease in the levels of this metabolite may indicate a disorder in the lysosomal enzyme system or an induction of the hydrolysis of this metabolite via an alternative route.35 The compound L-3-Amino-isobutanoic acid is produced from S-methylmalonate semialdehyde by the enzyme 4-aminobutyrate aminotransferase and can be indicative of pyrimidine metabolism.36–38
Plasma bisphenol a and phthalate levels in children with cerebral palsy: a case-control study
Published in International Journal of Environmental Health Research, 2022
Özlem Tezol, Sıddıka Songül Yalçin, Anıl Yirün, Aylin Balci Özyurt, Çetin Okuyaz, Pınar Erkekoğlu
Glucuronidase/aryl sulfatase enzyme (Helix pomatia, Lot No 5,210,722) was obtained from Roche (Mannheim, Germany). All other chemicals including bisphenol A (BPA, Lot No MKAA280 V) were from Sigma-Aldrich (St. Louis, MO). Mono-(2-ethylhexyl)-phthalate (MEHP, Unlabeled, Lot No ULM-4865-MT-12) was from LGC Standards (Teddington, UK). High-pressure liquid chromatography (HPLC) equipment was obtained from Agilent (Santa Clara, CA).