Nitroreductase-activated nitric oxide (NO) prodrugs.
Due to the involvement of nitric oxide (NO) in numerous and diverse physiological processes, site-directed delivery of therapeutic NO in order to minimize unwanted side-effects is necessary. O(2)-(4-Nitrobenzyl) diazeniumdiolates are designed as substrates for Escherichia coli nitroreductase (NTR), an enzyme that is frequently used to facilitate directed delivery of cytotoxic species to cancers. O(2)-(4-Nitrobenzyl) diazeniumdiolates are found to be stable in aqueous buffer but are metabolized by NTR to produce NO. A cell viability assay revealed that cytotoxic effects of O(2)-(4-nitrobenzyl)1-(2-methylpiperidin-1-yl)diazen-1-ium-1,2-diolate (4b) towards two cancer cell lines is significantly enhanced in the presence of NTR suggesting the potential for use of this compound in nitric oxide-based directed prodrug therapy.
Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, India.
Kavita
K
Sharma
Kundan
K
Sengupta
Harinath
H
Chakrapani
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000201:enzymology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009601:Nitroreductases / Q000378:metabolism*; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001391:Azo Compounds; D020030:Nitric Oxide Donors; D011355:Prodrugs; C452539:diazeniumdiolate; D009569:Nitric Oxide; D009601:Nitroreductases
Diazeniumdiolate; Directed prodrug therapy; Nitric oxide; Nitroreductase; Prodrug