Novel terpenoids, trichoderonic acids A and B isolated from Trichoderma virens, are selective inhibitors of family X DNA polymerases.
Trichoderonic acids A (1) and B (2), novel terpenoids, and (+)-heptelidic acid (3) isolated from cultures of a fungus, Trichoderma virens, and their structures were identified by spectroscopic analysis. These compounds selectively and competitively inhibited the activities of mammalian DNA polymerases beta, lambda (pols beta, lambda), and terminal deoxynucleotidyl transferase (TdT) in family X of pols, and compound 2 was a stronger inhibitor than compound 1 or 3. On the other hand, compounds 1-3 did not influence the activities of the other families (A-, B-, and the Y-families) of the mammalian pols tested, and showed no effect on the activities of plant pol alpha, fish pol delta, prokaryotic pol, or the other DNA metabolic enzymes tested. Compound 2 suppressed the growth of two human cancer cell lines, cervix carcinoma cells (HeLa) and breast carcinoma cells (MCF-7). The results suggest that these compounds identified inhibition among the families of mammalian pols.
Yamaguchi
Yasuhiro
Y
Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba, Japan.
Manita
Daisuke
D
Takeuchi
Toshifumi
T
Kuramochi
Kouji
K
Kuriyama
Isoko
I
Sugawara
Fumio
F
Yoshida
Hiromi
H
Mizushina
Yoshiyuki
Y
D000143:Acids / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D004253:DNA Nucleotidylexotransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase; D005260:Female; D005658:Fungi / Q000378:metabolism; D015751:Genes, pol; D006367:HeLa Cells; D006801:Humans; D012717:Sesquiterpenes; D013729:Terpenes / Q000037:antagonists & inhibitors; D014242:Trichoderma / Q000378:metabolism
D000143:Acids; D012717:Sesquiterpenes; D013729:Terpenes; C027285:heptelidic acid; C109534:DNA polymerase X; D004253:DNA Nucleotidylexotransferase; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase