dna topoisomerase i

Camptothecin (CPT) belongs to the alkaloid group of natural products and is a specific DNA topoisomerase I (Topo I) inhibitor (IC50=679 nM) with specificity. Camptothecin has antitumor activity and induces apoptosis.

Doxorubicin hydrochloride (Adriamycin) belongs to the anthracycline class of antibiotics and is an inhibitor of human DNA topoisomerase I II (IC50=0.8 2.67 μM). Doxorubicin hydrochloride exhibits cytotoxicity and antitumor activity. Doxorubicin hydrochloride reduces the phosphorylation of AMPK and its downstream target protein acetyl coenzyme A carboxylase, and induces apoptosis and autophagy.

Irinotecan Hydrochloride (CPT-11 hydrochloride) is the hydrochloride salt of a semisynthetic derivative of camptothecin. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Because ongoing DNA synthesis is necessary for irinotecan to exert its cytotoxic effects, it is classified as an S-phase-specific agent.

Irinotecan (CPT-11), a derivative of camptothecin, is an inhibitor of DNA topoisomerase I (Topo I). Irinotecan has antitumor activity by preventing DNA strand reattachment through binding to the Topo I complex, resulting in double-stranded DNA breaks and cell death.

Sophoridine (Dihydro-5-episophocarpine), a natural anticancer drug, has been used in China for decades. A series of novel N-substituted Sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure-activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential effect against four human tumor cell lines (liver, colon, breast, and lung). The mechanism of action of 6b is to inhibit the activity of DNA topoisomerase I, followed by the S-phase arrest and then cause apoptotic cell death, similar to that of its parent 1.

(S)-10-Hydroxycamptothecin (10-HCPT) is a DNA topoisomerase I inhibitor used as a clinical therapeutic agent against hepatoma.

SN-38 (NK012) is the active metabolite of Irinotecan, a DNA topoisomerase I (Topo I) inhibitor, which inhibits DNA and RNA synthesis (IC50=0.077 1.3 μM). SN-38 has antitumor activity and induces autophagy.

β-Lapachone (ARQ-501) is a specific DNA topoisomerase I inhibitor, and no inhibitory activities against DNA topoisomerase II or ligase.

Topotecan (NSC-609669) is a Topoisomerase I inhibitor,and is an antineoplastic agent used to treat ovarian cancer that works by inhibiting DNA topoisomerases.

Isodiospyrin is a novel human DNA topoisomerase I inhibitor, it exhibits cytotoxic activity to tumor cell lines. Isodiospyrin has antibacterial activity, the minimum inhibitory concentrations (MICs) against Gram-positive bacteria ranged from 0.78 to 50 mi

(±)-10-Hydroxycamptothecin (Hydroxy Camptothecine) is an alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase, type I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.

Rubitecan (9-Nitrocamptothecin) is a DNA topoisomerase I inhibitor. It inhibits DNA topoisomerase I and increases the fraction of supercoiled DNA in a cell-free assay in a concentration-dependent manner.Rubitecan is a semisynthetic agent related to camptothecin with potent antitumor and antiviral properties.

Groenlandicine is a protoberberine alkaloid from Coptidis Rhizoma. Groenlandicine exhibits moderate inhibitory effect with IC50 value of 154.2 μM for human recombinant aldose reductase (HRAR). Groenlandicine selectively induces topoisomerase I-mediated DN

Rebeccamycin is an antitumor antibiotic+ inhibits DNA topoisomerase I. Rebeccamycin appears to exert its primary antineoplastic effect by poisoning topoisomerase I. It also has a negligible effect on protein kinase C and topoisomerase II.

Erythro-Austrobailignan-6, an orally active anti-cancer agent, inhibits DNA topoisomerase I and II activity, induces cell apoptosis, and enhances the phosphorylation of p38 and JNK.

Podocarpusflavone A is a DNA topoisomerase I inhibitor with moderate anti-proliferative activity that induces cell apoptosis in MCF-7.