Premium
Cytotoxicity of Substituted Alkyl‐3,4‐bis(4‐methoxyphenyl)pyrrole‐2‐carboxylates in L1210 Lymphoid Leukemia Cells
Author(s) -
Burnham Bruce S.,
Gupton John T.,
Krumpe Keith,
Webb T.,
Shuford Jordan,
Bowers Brook,
Warren Amy E.,
Barnes Cheryl,
Hall Iris H.
Publication year - 1998
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(199811)331:11<337::aid-ardp337>3.0.co;2-r
Subject(s) - lymphoid leukemia , chemistry , dna , biochemistry , dna polymerase , dihydrofolate reductase , ribonucleoside , purine , nucleoside , enzyme , dna synthesis , nucleotide , polymerase , stereochemistry , biology , rna , leukemia , gene , genetics
Two alkyl‐3,4‐bis(4‐methoxyphenyl)pyrrole‐2‐carboxylates proved to be potent cytotoxic agents in the murine L1210 lymphoid leukemia screen. DNA synthesis was preferentially inhibited with the major target of the agents being de novo purine biosynthesis at the regulatory enzyme sites of PRPP‐amido transferase and IMP dehydrogenase. Other enzymatic activities which were suppressed by the drugs were DNA polymerase α, RNA polymerases, ribonucleoside reductase and dihydrofolate reductase. The d[NTP] pools, nucleoside kinase and the pyrimidine pathway were not affected by the presence of drugs. The DNA molecule itself was not the target of the agents, i.e. no alkylation of nucleotide bases, intercalation between bases or cross‐linking of DNA strands occurred. The agents did cause L1210 DNA fragmentation after 24 h incubation at 100 μM.