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Literature summary for 1.7.1.B2 extracted from

  • Green, L.K.; Syddall, S.P.; Carlin, K.M.; Bell, G.D.; Guise, C.P.; Mowday, A.M.; Hay, M.P.; Smaill, J.B.; Patterson, A.V.; Ackerley, D.F.
    Pseudomonas aeruginosa NfsB and nitro-CBI-DEI - a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy (2013), Mol. Cancer, 12, 58 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.7.1.B2

Application

Application Comment Organism
pharmacology Pseudomonas aeruginosa NfsB and nitro-CBI-DEI is a promising enzyme/prodrug combination for gene directed enzyme prodrug therapy Pseudomonas aeruginosa

Cloned(Commentary)

Cloned (Comment) Organism
gene nfsB, recombinant overexpression in Escherichia coli reporter strain SOS-R2, which contains a lacZ reporter gene under control of the SOS responsive promoter sfiA, functional nitroreductase NfsB expression in human HCT-116 cells Pseudomonas aeruginosa
gene nfsB, recombinant overexpression in Escherichia coli reporter strain SOS-R2, which contains a lacZ reporter gene under control of the SOS responsive promoter sfiA, functional nitroreductase NfsB expression in human HCT-116 cells Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Escherichia coli Escherichia coli nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA ?
-
 ?
additional information Pseudomonas aeruginosa Pseudomonas aeruginosa nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA ?
-
 ?

Organism

Organism UniProt Comment Textmining
Escherichia coli P38489
-
-
Pseudomonas aeruginosa Q9HTZ9
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5-(aziridin-1-yl)-2,4-dinitrobenzamide + NAD(P)H + H+ i.e. CB1954, an aziridinyl dinitrobenzamide prodrug Escherichia coli ? + NAD(P)+
-
 ?
5-(aziridin-1-yl)-2,4-dinitrobenzamide + NAD(P)H + H+ i.e. CB1954, an aziridinyl dinitrobenzamide prodrug, low activity Pseudomonas aeruginosa ? + NAD(P)+
-
 ?
additional information Escherichia coli nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA Escherichia coli ?
-
 ?
additional information Pseudomonas aeruginosa nitroreductase NfsB can reduce nitrochloromethylbenzindolines, i.e. nitro-CBIs, in an oxygen-independent fashion, generating highly cytotoxic metabolites that alkylate the N3 of adenine in the minor groove of DNA Pseudomonas aeruginosa ?
-
 ?
additional information an intrinsically oxygen-insensitive nature of the two-electron reduction mechanism Pseudomonas aeruginosa ?
-
 ?
additional information an intrinsically oxygen-insensitive nature of the two-electron reduction mechanism Escherichia coli ?
-
 ?
nitro-CBI-5-[(dimethylamino)ethoxy]indole + NAD(P)H + H+ a nitro-CBI prodrug, high activity Pseudomonas aeruginosa ? + NAD(P)+
-
 ?
nitro-CBI-5-[(dimethylamino)ethoxy]indole + NAD(P)H + H+ a nitro-CBI prodrug, low activity Escherichia coli ? + NAD(P)+
-
 ?

Synonyms

Synonyms Comment Organism
NfsB
-
 Pseudomonas aeruginosa
NfsB
-
 Escherichia coli
NfsB_Ec
-
 Escherichia coli
NfsB_Pa
-
 Pseudomonas aeruginosa

General Information

General Information Comment Organism
physiological function Escherichia coli NfsB expressing HCT-116 cells are 23.5fold more sensitive to prodrug nitro-CBI-DEI than pure cultures of untransfected cells, monolayer cytotoxicity assays using human colon carcinoma HCT-116 cells. The discrepancy in the fold-sensitivity to nitro-CBI-DEI between the two and three dimensional cytotoxicity assays stems from loss of activated drug into the media in the monolayer cultures Escherichia coli
physiological function Pseudomonas aeruginosa NfsB expressing HCT-116 cells are 540fold more sensitive to prodrug nitro-CBI-DEI than pure cultures of untransfected cells, the activated drug that they generate also displays an unprecedented local bystander effect, monolayer cytotoxicity assays using human colon carcinoma HCT-116 cells. The discrepancy in the fold-sensitivity to nitro-CBI-DEI between the two and three dimensional cytotoxicity assays stems from loss of activated drug into the media in the monolayer cultures Pseudomonas aeruginosa