Synthesis and anti-cancer potential of the positional isomers of NOSH-aspirin (NBS-1120) a dual nitric oxide and hydrogen sulfide releasing hybrid.
We recently reported the synthesis of NOSH-aspirin, a novel hybrid compound capable of releasing both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e., ortho-NOSH-aspirin. Here we report on the synthesis of meta- and para-NOSH-aspirins. We also made a head-to-head evaluation of the effects of these three positional isomers of NOSH-aspirin on colon cancer cell kinetics and induction of reactive oxygen species, which in recent years has emerged as a key event in causing cancer cell regression. Electron donating/withdrawing groups incorporated about the benzoate moiety significantly affected the potency of these compounds with respect to colon cancer cell growth inhibition.
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031, USA.
Federica
F
Vannini
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031, USA; EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews, Fife KY16 9ST, UK.
Andrew C
AC
MacKessack-Leitch
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031, USA.
Erin K
EK
Eschbach
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031, USA.
Mitali
M
Chattopadhyay
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031, USA.
Ravinder
R
Kodela
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031, USA; Avicenna Pharmaceuticals Inc., 555 West 57th Street, New York, NY 10019, USA. Electronic address: kashfi@med.cuny.edu.
Khosrow
K
Kashfi
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D015394:Molecular Structure; D009566:Nitrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
C571898:4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl 2-((4-(nitrooxy)butanoyl)oxy)benzoate; D000970:Antineoplastic Agents; D004220:Disulfides; D009566:Nitrates; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001241:Aspirin; D006862:Hydrogen Sulfide
Cell kinetics; Colon cancer; Hydrogen sulfide; NOSH-aspirin; Nitric oxide; Reactive oxygen species