Detail of "65-47-4"

Reference

Effects of acivicin and dichloroallyl lawsone upon pyrimidine biosynthesis in mouse L1210 leukemia cells

Effects of acivicin and dichloroallyl lawsone upon pyrimidine biosynthesis in mouse L1210 leukemia cells. Kemp, Anthony J.; Lyons, Stephen D.; Christopherson, Richard I. (Russell Grimwade Sch. Biochem., Univ. Melbourne, Parkville 3052, Australia). J. Biol. Chem., 261(32), 14891-5 (English) 1986. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 9 NSC 163501 (acivicin) [42228-92-2] and NSC 126771 (dichloroallyl lawsone) [36417-16-0] are potent inhibitors of nucleotide biosynthesis with consequent anticancer activity against certain exptl. tumors. To det. in detail the metabolic events induced by each inhibitor, a new 2-dimensional chromatog. procedure has been devised for measurement of the concns. of all pyrimidine intermediates and some purine nucleotides from 100 mL of an ext. of cells grown in the presence of [14C]bicarbonate. Addn. of acivicin (25 mM) to mouse L 1210 leukemia cells causes severe depletion in the cellular levels of CTP [65-47-4] and GTP [86-01-1], accumulation of uridine nucleotides, and abrupt but transient increases in the concns. of the early intermediates of both the pyrimidine and purine pathways. Addn. of dichloroallyl lawsone (25 mM) results in a rapid depletion of uridine and cytidine nucleotides; carbamyl aspartate [13184-27-5] and dihydroorotate [155-54-4] accumulate to high levels in an equil. ratio of 20.5:1, and orotate [65-86-1], orotidine [314-50-1], and UMP [58-97-9] increase transiently before decreasing to levels approaching their original steady states. The predominant inhibitory effects of acivicin are upon the reactions UTP [63-39-8] ? CTP and XMP [523-98-8] ? GMP [85-32-5], but there is also an initial transient activation of both the pyrimidine and purine pathways by acivicin. 58-97-9 and 56-65-5 are just another two chemicals used in this study. The data obtained with dichloroallyl lawsone are consistent with inhibition of the conversion of UMP ? UDP [58-98-0] initially followed by potent inhibition of dihydroorotate ? orotate. .

Inhibition of DNA primase by nucleoside triphosphates and their arabinofuranosyl analogs

Inhibition of DNA primase by nucleoside triphosphates and their arabinofuranosyl analogs. Parker, William B.; Cheng, Yung Chi (Dep. Pharmacol., Univ. North Carolina, Chapel Hill, NC 27514, USA). Mol. Pharmacol., 31(2), 146-51 (English) 1987. CODEN: MOPMA3. ISSN: 0026-895X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 7 DNA primase [64885-96-7] produces an RNA oligomer of approx. 10 bases, which is required by DNA polymerase a (EC 2.7.7.7) for the initiation of DNA synthesis. DNA primase was partially purified from acute lymphocytic leukemia cells from patients by using several chromatog. columns. Poly(dT) and poly(dC), but not poly(dA) or poly(dG), were good templates for ribonucleoside triphosphate (rNTP)-dependent DNA synthesis (i.e., DNA primase activity), and they were used in the study of the effect of natural and arabinofuranosyl nucleoside triphosphates on DNA primase activity. The Km for GTP [86-01-1] in the poly(dC) primase assay was ~175 mM. All noncomplementary natural rNTPs and deoxyribonucleoside triphosphates (dNTPs) inhibited poly(dC) primase activity to a similar extent (Ki values of ATP [56-65-5] and CTP [65-47-4] were 610 and 517 mM, resp.). 1-b-D-Arabinofuranosylcytosine 5'-triphosphate (araCTP) [13191-15-6] and 9-b-D-arabinofuranosyladenine 5'-triphosphate (araATP) [3714-60-1] were more potent inhibitors of poly(dC) primase activity than were CTP and ATP (Ki values were ~125 mM). AraCTP, araATP, CTP, and ATP inhibited DNA primase activity in a manner competitive with GTP. The concn. 3714-60-1 and 66097-68-5 are also in the experiment. required to inhibit poly(dC) DNA primase activity by 50% was detd. for a no. of arabinofuranosyl nucleoside triphosphate analogs, and the relative potency of inhibition of DNA primase activity was as follows: rNTP = dNTP = 5-aza-dCTP [72052-96-1] < ara-5-azaCTP [98204-39-8] = araTTP [66097-68-5] = araATP = araCTP < 2-fluoro-araATP [74832-57-8] = 2'-azido-2'-deoxy-araCTP [59652-91-4] < 2'-fluoro-araTTP [79551-89-6] = 2'-fluoro-5-iodo-araCTP [79570-63-1] = 2'-fluoro-5-methyl-araCTP [79570-62-0]. In the poly(dT) primase assay ATP did not follow classic Michaelis-Menten kinetics (ATP exhibited pos. cooperativity with a Hill coeff. of 2.0). However, this assay was very sensitive to araCTP (apparent Ki of 25 mM). In summary, these expts. suggested that DNA primase is controlled by the levels of ribonucleoside triphosphates, and that the perturbation of these pools by any agent could lead to the inhibition of DNA primase and thereby inhibit DNA synthesis. Furthermore, aranucleoside triphosphate analogs directly inhibited DNA primase, and it is possible that this effect may contribute to the cytotoxicity of these compds. .