Structure–activity relationships of epolactaene analogs as DNA polymerases inhibitors

Synthetic and Structure-Activity Relationship Studies on Bioactive Natural Products

“…Structure-activity relationships of epolactaene Our synthetic derivatives were evaluated for apoptosis-inducing activity in BALL-1 cells, 11,29,30) inhibitory activity against DNA polymerases and , 12,31) and anti-inflammatory activity 13) toward TPA-induced inflammation. The ,-epoxy--lactam moiety in the core and the length of the hydrophobic side chain influenced these activities (Fig.…”

Inhibition of DNA Polymerase λ Suppresses 12-O-Tetradecanoylphorbol- 13-Acetate-Induced Inflammation

“…On the other hand, since mice in which pol λ was knocked down were viable and fertile [40], the cell cycle-effect of petasiphenol and curcumin may be cytostatic. We reported that the other potent pol λ inhibitors, MAA, TA, EA and epolactaene derivatives, also suppressed cancer cell growth [9,17,22]. Therefore, the major mode of biochemical and cell biological action of them must be related to the TPA-induced inflammation-suppressive effect.…”

“…Epolactaene which is a neuritogenic compound found in human neuroblastoma cells and its derivative with a C18-straight alkyl side chain (epolactaene-C18) were chemically synthesized [11,22]. These compounds were identified and reported as mammalian pol α, pol β and DNA topoisomerase II (topo II) inhibitors [9,17,22]. We investigated the inhibitory effect of mammalian DNA polymerases and other DNA metabolic enzymes tested ( Table 1).…”

“…1F) [11] and its derivatives consisting of an epoxylactam ring and a C18-long chain group (Fig. 1G) [22] were inhibitors of mammalian pol α, pol β and DNA topoisomerase II (topo II) ( agents. Curcumin was well known not only to have a pol λ-inhibitory effect as described here but also as an inhibitor of chronic inflammation using TPA.…”

Transformation of thiols to disulfides by epolactaene and its derivatives

“…8,9 Recent evidence indicates that reactive oxygen species can act as signaling molecules by promoting the formation of disulfide bonds within or between select redox-sensitive proteins. 10 Epolactaene (1a), a microbial metabolite isolated from Penicillium sp., has several attractive biological activities such as promotion of neurite outgrowth and induction of G0/G1 cell cycle arrest in a human neuroblastoma cell line SH-SY5Y, [11][12][13][14] an apoptosisinducing activity in a human leukemia B cell line BALL-1, 15,16 inhibition of mammalian DNA polymerase and DNA topoisomerase activities, 17,18 and an anti-inflammatory activity on TPA (12-O-tetradecanoylphorbol 13-acetate)-induced inflammation. 19 We established an efficient synthesis of epolactaene via an oxiranyl anion derived from the a,b-epoxy-c-lactone.…”