Stereoselective Total Synthesis of Mucocin, an Antitumor Agent.

Takahashi, Shigetoshi; Kubota, Akemi; Nakata, Tadashi

doi:10.1002/chin.200319205

Cited by 2 publications

(4 citation statements)

References 3 publications

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“…Very little research, however, has been pursued on the inhibition of acetogenins against pol and topo activities until now, probably due to the small quantities of natural products. Since the total synthesis of bioactive acetogenins such as compound 5 could be possible (16)(17)(18)(19)(20)(21)(22)(23)(24), these compounds should be provided and studied in pharmaceutical research throughout the world.…”

Section: Discussionmentioning

confidence: 99%

“…Eight chemically synthesized acetogenins (i.e., compounds 1-8; Fig. 1) were employed (16)(17)(18)(19)(20)(21)(22)(23)(24). Nucleotides and chemically synthesized DNA template-primers, such as poly(dA), poly(rA), and oligo(dT) 12-18 , and radioisotope reagents, such as [ 3 H]-dTTP (2'-deoxythymidine 5'-triphosphate) (43 Ci/mmol), [methyl-3 H]-thymidine, [5, H]uridine and L-[4,5-3 H]-leucine, were purchased from GE Healthcare Bio-Science Corp. (Buckinghamshire, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Besides such classical types, acetogenins with a tetrahydropyran (THP) ring in the long chain such as mucocin (compound 1), jimenezin (compound 2), muconin (compound 4), pyranicin (compound 5), and pyragonicin (compound 6) have also been discovered (12)(13)(14)(15). Recently, we have been interested in the non-classical THP acetogenins because of the powerful antitumor activity, and achieved total synthesis of the natural and non-natural acetogenins (compounds 1-8) (16)(17)(18)(19)(20)(21)(22)(23)(24). In connection with our studies on a search for new pol and topo inhibitors and development of new anticancer drugs, we initiated biological studies of these acetogenins.…”

Section: Introductionmentioning

confidence: 99%

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Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth

Takahashi

Yonezawa²,

Kubota³

et al. 2008

Int J Oncol

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This report describes the inhibitory activities of the natural and non-natural acetogenins [mucocin (compound 1), jimenezin (compound 2), 19-epi jimenezin (compound 3), muconin (compound 4), pyranicin (compound 5), pyragonicin (compound 6), 10-epi pyragonicin (compound 7), and a γ-lactone (compound 8)], which were synthesized by us, against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compound 5 was revealed to be the strongest inhibitor of the animal pols and human topos tested, and the IC 50 values for pols and topos were 2.3-15.8 and 5.0-7.5 μM, respectively. The compound also suppressed human cancer cell (promyelocytic leukemia cell line, HL-60) growth with the same tendency as the inhibition of pols and topos and the LD 50 value was 9.4 μM. Compound 5 arrested the cells at G2/M and G1 phases, and prevented the incorporation of thymidine into the cells, indicating that it blocks DNA replication by inhibiting the activity of pols and topos. This compound also induced apoptosis of the cells. Based on these results, the action mode of compound 5 is discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth

Takahashi

Yonezawa²,

Kubota³

et al. 2008

Int J Oncol

Self Cite

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“…Takahashi and Nakata published two distinct total syntheses of mucocin both in 2002. In the first reported approach the natural product was assembled from two major fragments, the more complex bis-cyclic ether fragment 167 deriving from (4 E ,8 E )-dodeca-4,8-dienedial ( Figure 22 ) [ 100 ].…”

Section: Total Synthesis Of Non-adjacent Thf-thp Acetogeninsmentioning

confidence: 99%