Synthesis and anti-cancer potential of the positional isomers of NOSH-aspirin (NBS-1120) a dual nitric oxide and hydrogen sulfide releasing hybrid

• Published in: Bioorganic & medicinal chemistry letters Vol. 25; no. 20; pp. 4677 - 4682
• Main Authors: Vannini, Federica, MacKessack-Leitch, Andrew C., Eschbach, Erin K., Chattopadhyay, Mitali, Kodela, Ravinder, Kashfi, Khosrow
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-10-2015
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Aspirin - analogs & derivatives; Aspirin - chemical synthesis; Aspirin - chemistry; Aspirin - pharmacology; Cell Cycle - drug effects; Cell kinetics; Cell Line, Tumor; Cell Proliferation - drug effects; Colon cancer; Disulfides - chemical synthesis; Disulfides - chemistry; Disulfides - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HT29 Cells; Humans; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Molecular Structure; Nitrates - chemical synthesis; Nitrates - chemistry; Nitrates - pharmacology; Nitric oxide; Nitric Oxide - metabolism; NOSH-aspirin; Reactive oxygen species; Reactive Oxygen Species - metabolism; Structure-Activity Relationship; Hydrogen sulfide; NOSH-aspirin; Reactive oxygen species; Colon cancer; Cell kinetics; Nitric oxide
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.08.023

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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.