Topoisomerase

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.

Etoposide (VP-16-213) is a topoisomerase II inhibitor that inhibits DNA synthesis by forming a complex with topoisomerase II and DNA (IC50=60.3 μM). Etoposide has antitumor activity and induces apoptosis and autophagy.

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.

Exatecan Mesylate (DX8951f) is a DNA topoisomerase I inhibitor (IC50: 2.2 μM, 0.975 μg/mL).

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

Prulifloxacin (NM441) is a broad-spectrum fluoroquinolone antibiotic. It Inhibits bacterial DNA synthesis by inhibiting the activity of bacterial DNA topoisomerase II and IV.

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.

EIDD-1931 (Beta-d-N4-hydroxycytidine) is a ribonucleoside analog with antiviral activity.It inhibits replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in Vero 76 cells, Middle East respiratory syndrome coronavirus (MERS-CoV) in Calu-3 2B4 cells, and SARS-CoV-2 in Vero cells (IC50s =0.1, 0.15 and 0.3 μM, respectively)

Ciprofloxacin monohydrochloride (Bay-09867 hydrochloride) is a broad-spectrum antimicrobial carboxyfluoroquinoline.

Norfloxacin (MK-0366)(Norxacin) is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.

Chloroquinoxaline sulfonamide (Chloroquinoxaline) is a topoisomerase II alpha/beta toxin with antitumor activity and immunosuppressive properties that inhibits the proliferation of B16 melanoma cells in mice, and can be used to study metastatic colorectal cancer. It can be used to study metastatic colorectal cancer.

NU2058 (O(6)-Cyclohexylmethylguanine) is a guanine-based CDK inhibitor, also inhibits DNA topoisomerase II ATPase activity.

Berberine chloride (Natural Yellow 18) is an alkaloid from Hydrastis canadensis L., Berberidaceae and also found in many other plants. It is relatively toxic to parenterally but has been used orally for various fungal and parasitic infections and an anti-diarrheal.

Bimolane is a topoisomerase II inhibitor.

Razoxane is used as an antimitotic agent with immunosuppressive properties.

Gimatecan HCl (ST1481 HCL) is a potent topoisomerase I inhibitor. Gimatecan is an orally bioavailable camptothecin analogue with antitumor activity.

Oxaquin TEA (MCB-3837 TEA), a precursor compound to MCB3681, is a DNA topoisomerase inhibitor that can be used to study Clostridium difficile infections and cross-infections.

Simmitecan hydrochloride is a camptothecin derivative, a topoisomerase I inhibitor with anticancer activity, which can be used to study is solid tumors.

Topovale (ARC111) is a potent inhibitor of topoisomerase I. Topovale inhibits hypoxia-mediated accumulation of hypoxia-inducible factor-1alpha. Topovale exhibited low nM cytotoxicity against a panel of cancer cells. Topovale cytotoxicity as well as Topovale-induced apoptosis was reduced > 100-fold in CPT-resistant topoisomerase I (TOP1)-deficient P388/CPT45 cells as compared with P388 cells.

F-14512 (free base) is a topoisomerase II inhibitor for the study of acute myeloid leukemia.

Leurubicin (N-Leucyldoxorubicin) is a potential Top II inhibitor for the study of bacterial infections .

Daniquidone (Batracylin) is a potent dual inhibitor of DNA topoisomerase I and DNA topoisomerase II with cytotoxic and antiproliferative activity that induces DNA fragmentation for the study of neoplasms, immune disorders, and lymphatic disorders.

Alalevonadifloxacin is a DNA gyrase and DNA topoisomerase inhibitor and a novel antibacterial compound of the quinolone class targeting MRSa. Alalevonadifloxacin is potentially useful in the treatment of bacterial Gram-positive, Gram-negative and anaerobic infections.

Aldoxorubicin hydrochloride is an albumin-binding prodrug of Doxorubicin, a DNA topoisomerase II inhibitor. Aldoxorubicin hydrochloride is released from albumin under acidic conditions. Aldoxorubicin hydrochloride exhibits potent antitumor activities in various cancer cell lines and in murine tumor models.

Tubulin inhibitor 35 (Tubulin IN 35) is a potent dual inhibitor of topoisomerase I and microtubule protein polymerization with antitumor activity, inhibits migration and invasion of MGC-803 and RKO cell lines, interrupts the cell cycle and induces apoptosis.

Topixantrone 2HCl is a DNA topoisomerase inhibitor with antitumor activity for the study of gastric and prostate cancer.

Topoisomerase II inhibitor 14 is a potent topoisomerase II inhibitor with anticancer and antioxidant activities.Topoisomerase II inhibitor 14 induces apoptosis and blocks the cell cycle in S phase.Topoisomerase II inhibitor 14 reduces the amount of GSH, MDA and NO. Topoisomerase II inhibitor 14 reduces the amount of GSH, MDA and NO.

Pegamotecan (PEG-camptothecin) is a topoisomerase I (TOP1) inhibitor with anticancer activity, and it is used in the treatment of esophageal, non-small cell lung and pancreatic cancers.

XR 5944 is an antitumor compound that targets DNA, is a topoisomerase inhibitor, inhibits ER activity, and can be used to study colon and lung cancer.

XR-11576 HCl is a novel orally active dual topoisomerase I and II inhibitor with antitumor activity.

(4-NH2)-Exatecan is a topoisomerase inhibitor with potential anticancer activity for the synthesis of antibody drug conjugates (ADCs).

Gimatecan (STI481) is a potent topoisomerase I inhibitor. Gimatecan is an orally bioavailable camptothecin analogue with antitumor activity.

DRF-1042 is an orally active camptothecin analog with antitumor activity and inhibits DNA topoisomerase I. It is used in the study of refractory tumors.

Ellipticine (Elliptisine) is a potent antineoplastic agent exhibiting multiple mechanisms of action, IC50 of 0.67±0.06, 1.25±0.13, 1.25±0.13, 0.67±0.06, 0.27±0.02, 0.49±0.04, 0.44±0.03, and 1.48±0.62 μM for Leukemia HL-60, Breast adenocarcinoma MCF-7, Breast adenocarcinoma MCF-7, Leukemia HL-60, Neuroblastoma IMR-32, Neuroblastoma UKF-NB-4, Neuroblastoma UKF-NB-3, and Glioblastoma U87 mg cell, respectively.

Pyrazoloacridine (PD 115934) is a nucleic acid binding agent that inhibits the activity of topo I and II with an IC50 of 1.25 μM in K562 cells. Pyrazoloacridine shows anti-cancer activity.

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

Amsacrine (AMSA) (mAMSA) an antineoplastic agent which can intercalate into the DNA of tumor cells. Amsacrine also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II.

Mitoxantrone (mitozantrone) is an anthracenedione antibiotic with antineoplastic activity. Mitoxantrone intercalates into and crosslinks DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, resulting in DNA strand breaks and inhibition of DNA repair. Mitoxantrone is less cardiotoxic compared to doxorubicin.

Doxorubicin (Adriamycin) is a Topoisomerase II (Top2) inhibitor with antineoplastic activity.

Teniposide (VM26), a semisynthetic derivative of podophyllotoxin with antitumor activity, inhibits DNA synthesis by forming a complex with topoisomerase II and DNA.

Aldoxorubicin has effective antitumor activities in various cancer cell lines and in murine tumor models. Aldoxorubicin is an albumin-binding prodrug of Doxorubicin (DNA topoisomerase II inhibitors).

Epirubicin hydrochloride (Pharmorubicin) is an antineoplastic agent which can inhibit Topoisomerase.

Betulinic acid (ALS-357) is a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase.

Levofloxacin (Fluoroquinolone) is a broad-spectrum antibiotic topoisomerase II and topoisomerase IV inhibitor, used to treat respiratory, urinary tract, gastrointestinal, and abdominal infections.

Ellipticine hydrochloride (NSC-71795 (hydrochloride)) is a potent antineoplastic agent; inhibits DNA topoisomerase II activities.

Pirarubicin (Theprubicin) is an anthracycline antibiotic. It is also a DNA RNA synthesis inhibitor that intercalates into DNA and interacts with topoisomerase II, utilized as an antineoplastic agent.

Ellagic acid (Gallogen) is a fused four ring compound isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye.

Ofloxacin (Oxaldin) is a fluoroquinolone antibacterial antibiotic. Ofloxacin binds to and inhibits bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, enzymes involved in DNA replication and repair, resulting in cell death in sensitive bacterial species.

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

Idarubicin hydrochloride (Zavedos), a hydrochloride salt form of Idarubicin, is a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells ( IC50: 3.3 ng mL).