• Journal of Microbiology and Biotechnology
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• 제8권1호
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• pp.89-91
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• 1998

Cryptotanshinone induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, whereas topoisomerase II-mediated DNA cleavage was not induced by this agent. In DNA relaxation assay using calf thymus DNA topoisomerase I and supercoiled pBR322 DNA, cryptotanshinone inhibited topoisomerase I-mediated DNA relaxation in a dose-dependent manner. In unwinding assay, cryptotanshinone ($50{\mu}M$) did not shift the topoisomers of DNA. These results suggest that cryptotanshinone exerted a preferential inhibition of topoisomerase I without intercalating into DNA.

• Journal of Microbiology and Biotechnology
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• 제12권6호
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• pp.1013-1016
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• 2002

Cyclo(L-prolyl-L-phenylalanyl) [cyclo(pro-phe)] was isolated from Streptomyces sp. AMLK-335 and found to inhibit DNA topoisomerase I activity. In a DNA relaxation assay using supercoiled pBR322 DNA, cyclo(pro-phe) inhibited the DNA topoisomerase activity more strongly than camptothecin, a known topoisomerase inhibitor. However, at a concentration of $10{\mu}M$, cyclo(pro-phe) produced a lower degree of DNA relaxation than camptothecin, therefore, the inhibition of topoisomerase I activity by cyclo(pro-phe) was also found to be dose dependent. Accordingly, the current results suggest that cyclo(pro-phe) may be a novel inhibitor of topoisomerase I.

• 약학회지
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• 제44권4호
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• pp.358-361
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• 2000

Parameter focusing on the DNA topoisomerase-Iinhibition with X-substituted phenyl substituents in 1-(2-furyl)-3-phenylpropenone derivatives as inhibition material were analyzed. From the basis on the results the inhibition on DNA topoisomerase I suggested that the inhibition activities of X-substituted phenyl substitutents would depend largely on the net charge of $\beta$-carbon atom, LUMO energy (e.v.) and STERIMOL parameter B$_{5}$ (width) of X. Among them, non-substituent (X=H), 1 and 2,2-dichloro substituent, 4 showed the highest DNA topoisomerase-I inhibition activity.y.

• 한국식품영양과학회지
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• 제29권5호
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• pp.917-921
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• 2000

This study was carried out to investigate the effects on the mutagenicity and activity of DNA topoisomerase I of Sarcodon aspratus. Using an Ames mutagenicity test, which has been used to assess both mutagenic and antimutagenic effects of various molecules, it was observed that the methanol extracted fraction and other fractions (prepared in water or ethylacetate) of Sarcodon aspratus showed a significant antimutagenic activity against a mutagenecity induced by both a direct mutagenic agent such as MNNG and an indirect mutagenic agents such as B(a)P and AFB$_1$in Salmonella typhimurium TA98, TA100. Also, the extract and fractions of Sarcodon aspratus were found to have an inhibitory activity on the relaxation process of DNA topoisomerase I.

• 한국미생물·생명공학회지
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• 제23권2호
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• pp.123-130
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• 1995

DNA topoisomerase I have been shown to be important therapeutic target in cancer chemotherapy. Chemotaxonomy and numerical identification were carried out for an isolate strain No.7489 producing an antibiotic that inhibits DNA topoisomerase I activity. The genus of strain No.7489 was determined as Streptomyces sp. from culture, morphological and chemotaxonomic data. Thirty-nine taxonomic unit characters were tested and the data were analyzed numerically using the TAXON program. The isolate was best matched to Streptomyces melanosporofaciens in the major cluster 32 of Streptomyces. Therefore, it was concluded that the isolate was identified to be a member of Streptomyces melanosporofaciens.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.562-570
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• 2021

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

• 약학회지
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• 제40권6호
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• pp.697-704
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• 1996

Quinolone derivatives, SJ5b (ethyl 5,12-dihydro-5-dihydro-5-oxobenzoxazolo[3,2-a]quinoline-6-carboxylate) and SQ7b (3-fluoro-2-(4-methylpiperazin-1-yl)-5.12-dihydro-5-oxobenzoxa zolo[3,2-a]quinoloine carboxylic acid) showed in vitro cytotoxicities against various tumor cell lines. SJ5b and SQ7b completely inhibited the DNA relaxation activities of human placental topoisomerase II at the concentration of 15.63 and 1.95 ${\mu}$g/ml, respectively. However, unlike etoposide which stabilize the topoisomerase II-DNA complex, SQ7b did not cause topoisomerase II-mediated DNA cleavage and SJ5b weakly stabilized the topoisomerase II-DNA cleavable complex. Through both experiments. DNA relaxation assay by the increment of topoisomerase II concentration and DNA unwinding assay, it was shown that SJ5b and SQ7b did not interact with topoisomerase II itself but bound to DNA. Therefore, it was concluded that DNA binding of SJ5b and SQ7b caused the inhibition of topoisomerase II related to DNA relaxation but no or very weak stabilization of topoisomerase II-DNA cleavable complex. In addition, SJ5b and SQ7b prevented whole cell nucleic acid syntheses in HL60 cells.

• 생명과학회지
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• 제10권6호
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• pp.621-629
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• 2000

Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA “cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT. CPT.

• Journal of Microbiology and Biotechnology
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• 제6권5호
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• pp.366-367
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• 1996

Dibutyl phthalate induced topoisomerase Ⅰ mediated DNA relaxation comparable to that of camptothecin, and topoisomerase Ⅱ mediated DNA relaxation equipotent to that of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA). The relaxation activities of dibutyl phthalate were dose-de-pendent and nearly as potent as those of camptothecin and m-AMSA.

• 한국식품과학회지
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• 제29권5호
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• pp.1057-1062
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• 1997

26속 32종의 버섯의 topoisomerase II 작용 억제여부를 검색한 결과 말불버섯이 topoisomerase II 작용을 억제하며 그 유효 성분이 핵산분획물에 존재함을 확인하였다. 말불버섯의 핵산분획물은 linear DNA와 open circular DNA를 생성시켰으며 농도와 반응시간에 의존적인 반응 양상을 나타냈다. 또한 말불버섯의 핵산분획물은 topoisomerase I의 작용도 억제하였다. 그러나 배양한 말불버섯의 균사체는 topoisomerase 작용에 아무런 영향을 미치지 않았다.