• Korean Journal of Pharmacognosy
• /
• v.30 no.1
• /
• pp.1-6
• /
• 1999

To evaluate cytotoxic effect and topoisomerase I inhibition activity of Caesalpinia sappan L., both water and methanol extracts were examined using in vitro assay. The cytotoxic effect of Caesalpinia sappan L. examined using MTT and SRB assay and $IC_{50}$ values were measured against U937, HL60, HepG2, SNU-1, SNU-16 cancer cell lines. Among them the representative cytotoxic results are shown as follows; water extract (U937=13.39 ${\mu}g/ml$, HL60=8.65 ${\mu}g/ml$, HepG2=38.48 ${\mu}g/ml$, SNU-1=7.72 ${\mu}g/ml$, SNU-16=25.49 ${\mu}g/ml$), methanol extract (U937=13.35 ${\mu}g/ml$, HL60=9.43 ${\mu}g/ml$, HepG2=25.67 ${\mu}g/ml$, SNU-1=8.37 ${\mu}g/ml$, SNU-16=28.64 ${\mu}g/ml$). The inhibitory concentration of DNA topoisomerase I activity against water extract was 100 ${\mu}g/ml$ and the inhibitory concentration of DNA topoisomerase I against methanol extract was 400 ${\mu}g/ml$.

• YAKHAK HOEJI
• /
• v.49 no.5
• /
• pp.428-436
• /
• 2005

DNA topoisomerase I(TOP1) helps the control of DNA replication, transcription and recombination by assist­ing breaking and rejoining of DNA double strand. Camptothecin (CPT) and its derivative, topotecan, are known to inhibit TOP1 by intercalating into TOP1-DNA complex. Recently various non-CPT intercalators are synthesized for a new class of TOP1 inhibitors. In this study, six compounds isolated from Poria cocos were investigated for their interaction with TOP1­DNA complex using the flexible docking program, FlexiDock. The binding modes were analyzed and compared with the TOP1 inhibition activities. The compounds that showed potent activity were intercalated between the + 1/-1 base pairs of DNA, located near the active site phosphotyrosine723 and formed hydrogen bonds with active site residues. On the other hand, compounds with no activity were not docked at all. The binding modes were well correlated with the inhibition activity, suggesting the possibility that potent inhibitors can be designed from the information presented by the docking study.

• Journal of Life Science
• /
• v.10 no.6
• /
• pp.621-629
• /
• 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.

• YAKHAK HOEJI
• /
• v.40 no.6
• /
• pp.697-704
• /
• 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.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.10
• /
• pp.3073-3082
• /
• 2013

Designed and synthesized twenty-four 2,4-diaryl benzofuro[3,2-b]pyridine derivatives were evaluated for topoisomerase I and II inhibitory activities as well as cytotoxicities against several human cancer cell lines. Various aryl groups such as phenyl, 2- or 3- furyl, 2- or 3-thienyl, and 2-pyridyl were substituted at 2- or 4- position of central pyridine. Compounds 8, 12, 13, and 14, with 2-furyl either at 2- or 4- position of central pyridine showed the significant topoisomerase II inhibitory activity at 100 ${\mu}M$.

• Korean Journal of Food Science and Technology
• /
• v.29 no.5
• /
• pp.1057-1062
• /
• 1997

In the course of searching for anticancer agents from 32 mushrooms, it was found that methanol extract of Lycoperdon perlatum showed inhibitory effect on topoisomerase II-mediated DNA cleavage. This active methanol extract was sequentially fractionated with hexane, chloroform, n-buthanol and water. Among the solvent-fractionated extracts, $1\;{\mu}g/mL$ hexane fraction of L. perlatum inhibited on topoisomerase II-mediated DNA cleavage. The effect of hexane fraction of L. perlatum was dose- and reaction time-dependent. The hexane fraction of L. perlatum was found to have inhibitory activity on relaxation assay of DNA topoisomerase I. The hexane fraction of cultured L. perlatum, however, had no inhibitory effect on either type of topoisomerase.

• Archives of Pharmacal Research
• /
• v.21 no.6
• /
• pp.729-733
• /
• 1998

The crude extract of Streptomyces sp. strain KM86-9B, isolated from a marine sponge, displayed significant inhibition on topoisomerase I activity. Investigation of the ca usative components by bioactivity-directed fractionation resulted in the isolation of a series of iso- and anteiso-fatty acids.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.10
• /
• pp.3566-3570
• /
• 2011

A series of 2,4,6-tripyridyl pyridines were synthesized, and evaluated for their antitumor cytotoxicity, topoisomerase I and II inhibitory activity. From the eighteen prepared compounds, compounds 10-12 have shown better or similar cytotoxicity against several human cancer cell lines as compared to 2,2':6',2"-terpyridine and doxorubicin. Especially, compound 10 exhibited the most potent cytotoxicity better than positive controls. Structure-activity relationship study indicated that 2,2':6',2"-terpyridine skeleton has an important role in displaying significant cytotoxicity against several human cancer cell lines.

• Archives of Pharmacal Research
• /
• v.27 no.8
• /
• pp.829-833
• /
• 2004

The bioactivity-guided fractionation of the methylene chloride extract of the sclerotium of Poria cocos led to the isolation of (S)-(＋)-turmerone (1), ergosterol peroxide (2), polyporenic acid C (3), dehydropachymic acid (4), pachymic acid (5), and tumulosic acid (6). Compounds 4-6 exhibited moderate cytotoxicities, with $IC_{50}$ values of 20.5, 29.1, and $10.4{\;}\mu\textrm{m}$, respectively, against a human colon carcinoma cell line. However, 3-6 not only showed inhibitory activities as potent as etoposide used as a positive control on DNA topoisomerase II (36.1, 36.2, 43.9 and 66.7％ inhibition at a concentration of $20{\;}\mu\textrm{m}$, respectively), but also inhibition of DNA topoisomerase I (55.8, 60.7, 43.5, and 83.3％ inhibition at a concentration of $100{\;}\mu\textrm{m}$, respec-tively).

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.180.1-180.1
• /
• 2003

Eukaryotic DNA topoisomerase I (top I) is an essential enzyme that act to relax supercoiled DNA during the transcription, replication and mitosis. Intracellular levels of top I are elevated in a number of human solid tumors, relative to the respective normal tissues, suggesting that controlling the topI level is important to treat cancer. Top I poisons show their antitumor activities by stabilizing the cleavable ternary complex consisting of top I enzyme, DNA, and drug. Thus, top I is a promising target for the development of new cancer chemotherapeutics against a number of solid tumors. (omitted)