Interaction of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride with nucleic acids and proteins

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…711 The former reaction was attributed to the alkylation of nucleic acids by either the ClCH 2 CH 2 NdNOH or ClCH 2 CH 2 + species, and the latter to protein carbamoylation by the cyclohexyl isocyanate (pathway A, Scheme 91). Similar results were obtained with 14 C-labeled BCNU (21) 712 and ACNU (311) 713 and EBNU (90). 141,142 A 14 C-labeled CdO group of EBNU (1025, Chart 28) was found 141 to be bound to cytoplasmic and nuclear proteins but not to nucleic acids of L1210 cells, whereas a 14 of the [ 14 C]cyclohexyl-CCNU (939) because the reaction of 1025 can yield two carbamoylating species per molecule.…”

“…Similar results were obtained with 14 C-labeled BCNU ( 21 ) and ACNU ( 311 ) and EBNU ( 90 ). , A 14 C-labeled CO group of EBNU ( 1025 , Chart ) was found 141 to be bound to cytoplasmic and nuclear proteins but not to nucleic acids of L1210 cells, whereas a 14 C-labeled 1,2-ethanediyl-EBNU ( 1026 ) was bound to both proteins and nucleic acids. The radiolabeling reactions of 1026 are alkylations, resulting from an intermediate ethanediylbis(diazohydroxide), HONN(CH 2 ) 2 NNOH, while the radiolabeling reactions of 1025 are carbamoylations from the unstable carbamic acid intermediate H 2 NC(O)OH.…”

“…Similar binding studies of 1026 with nucleic acids and synthetic nucleotides revealed 141 a strong preference for RNA over DNA and of poly G and poly C over poly A and poly U. However, CCNU ( 137b ) was bound to poly G and poly C to the same extent, BCNU ( 33 ) was bound to poly C almost 6 times greater than poly G, and ACNU ( 311 ) was bound to DNA almost four times greater than RNA …”

“…However, CCNU (137b) was bound to poly G and poly C to the same extent, 711 BCNU (33) was bound to poly C almost 6 times greater than poly G, 712 and ACNU (311) was bound to DNA almost four times greater than RNA. 713 Thus each CENU analog has a different specificity for the binding of nucleic acids and polynucleotides.…”

A randomized prospective study of radiation versus radiation plus acnu in inoperable non-small cell carcinoma of the lung

“…8 After intravenous injection of ACNU labeled with carbon 14 (I4C) in either pyrimidine or ethylene moieties into tumor-bearing mice or healthy rats, radioactivity was rapidly distributed in tumor tissues and different organs, and almost excreted into urine within 24 h o u r~.~* l~…”