dna topoisomerase 1

DNA topoisomerase II inhibitor 1 is a potent inhibitor of DNA topoisomerase II that arrests the cell cycle in sub-G1 phase and induces apoptosis with anti-value-added effects.

Irinotecan hydrochloride trihydrate (CPT-11 HCl Trihydrate) keeps DNA from unwinding by inhibiting topoisomerase 1.

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.

3-Hydroxypyridine exhibits inhibitory activity against DNA topoisomerase 2-beta (Topo IIβ) and HIV-1 replication in Sup-T1 cells, making it useful for studying the HIV-1 virus.

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.

1,4-Naphthoquinone (P-Naphthoquinone) was used as a potential inhibitor of monoamine oxidase and DNA topoisomerase activities[2]. It was also used to inhibit the acetyltransferase activity[1].

LMP744 hydrochloride (NSC-706744 hydrochloride) is a DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity. 

Trovafloxacin, a broad-spectrum quinolone antibiotic, exhibits potent activity against Gram-positive bacteria.

Trovafloxacin is a broad-spectrum fluoroquinolone antibiotic that inhibits the activity of DNA gyrase and topoisomerase IV, enzymes involved in DNA replication. It also acts as an effective and specific inhibitor of the pannexin 1 channel (PANX1, IC50 = 4 μM).

Hycanthone (Etrenol(mesylate)) is a potent drug of antischistosomal. Hycanthone is a DNA intercalator that inhibits RNA synthesis and DNA topoisomerases I and II. Hycanthone inhibits nucleic acid biosynthesis and inhibits APE1 via direct protein binding(KD: 10 nM).

Daunorubicinol, a potent antitumor drug-linker conjugate for antibody-drug conjugate (ADC) applications, utilizes Aur0101 (DNA Topoisomerase II inhibitor) connected through the ADC linker[1].

MAC glucuronide phenol-linked SN-38, a pH-sensitive lactone and DNA topoisomerase I inhibitor drug linker, exhibits cytotoxicity in L540cy and Ramos cells, with IC50 values of 113 ng/mL and 67 ng/mL, respectively[1].

Compound AuL9, also known as iNOS/TopoI-IN-1, is a multi-target hybrid molecule possessing anti-tumor, anti-inflammatory, and antioxidant properties. This compound effectively inhibits the growth of MCF-7 and MDA MB-231 breast cancer cells in vitro, exhibiting IC50 values of 3.5 μM and 6.3 μM respectively. It also prompts DNA damage and apoptosis in these cells by inhibiting human topoisomerase I (TopoI) with a K_i of 2.72 μM. Additionally, iNOS/TopoI-IN-1 reduces the expression of iNOS by suppressing the activation of NF-kB, with a K_i of 1.49 μM.

DNA gyrase/Topo IV-IN-1 (Compound 27) is an inhibitor of DNA gyrase and topoisomerase IV with antibacterial properties. It exhibits IC50 values of 11 and 17 nM against the DNA gyrase of Escherichia coli and methicillin-resistant Staphylococcus aureus, respectively, and IC50 values of 83 and 21 nM against topoisomerase IV of the same organisms. DNA gyrase/Topo IV-IN-1 is applicable in anti-infective research.

Antibacterialagent 272 (Compound Z22) is a potential antibacterial agent that targets the DNA and DNA-topoisomerase II (DNA-Topo II) complex. It exhibits strong antibacterial activity, with a minimum inhibitory concentration (MIC) of 1 μg/mL against Staphylococcus aureus 25923 and 29213, 2 μg/mL against Staphylococcus epidermidis 12228, 2-4 μg/mL against Enterococcus faecalis, and 4 μg/mL against Pseudomonas aeruginosa 9027 and 27853. Antibacterialagent 272 binds by intercalating between DNA base pairs, disrupting the normal function of bacterial DNA, and is suitable for research into bacterial infectious diseases.

TOP3B-IN-1 (NSC-260610) is an inhibitor of topoisomerase IIIβ (TOP3B). This compound does not induce the formation of cleavage complexes (TOP3Bccs) between TOP3B and DNA or RNA and instead disrupts these complexes. TOP3B-IN-1 can serve as a control compound in the research and development of inhibitors targeting TOP3B.

DS-8587 is a DNA topoisomerase inhibitor. DS-8587 exhibits potent antibacterial activity against quinolone-resistant A. baumannii isolates that harbor mutations in quinolone resistance-determining regions. DS-8587 significantly reduces the number of viabl

AZD 1152 is an orally bioavailable prodrug of AZD 1152-HQPA, a selective inhibitor of Aurora kinase B (IC50= 0.36 nM).1AZD 1152 is converted to AZD 1152-HQPA in plasma. Inhibition of Aurora B results in disruption of spindle checkpoint functions and chromosome alignment, resulting in inhibition of cytokinesis followed by apoptosis.2,3AZD 1152 inhibits tumor xenograft growthin vivo.4,5 1.Mortlock, A.A., Foote, K.M., Heron, N.M., et al.Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinaseJ. Med. Chem.50(9)2213-2224(2007) 2.Popescu, R., Heiss, E.H., Ferk, F., et al.Ikarugamycin induces DNA damage, intracellular calcium increase, p38 MAP kinase activation and apoptosis in HL-60 human promyelocytic leukemia cellsMutation Research709-71060-66(2011) 3.Moore, A.S., Blagg, J., Linardopoulos, S., et al.Aurora kinase inhibitors: Novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemiasLeukemia24(4)671-678(2010) 4.Wilkinson, R.W., Odedra, R., Heaton, S.P., et al.AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosisClin. Cancer. Res13(12)3682-3688(2007) 5.Yang, J., Ikezoe, T., Nishioka, C., et al.AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivoBlood110(6)2034-2040(2007)

TAS-103 is a dual inhibitor of DNA topoisomerase I/II, utilized in cancer research.

ARN-21934 is a potent, highly selective, blood-brain barrier (BBB) penetrant inhibitor for human topoisomerase II α over β. It inhibits DNA relaxation with an IC50 of 2 μM, compared to 120 μM for Etoposide. ARN-21934 exhibits favorable in vivo pharmacokinetic properties and shows promise in anticancer research, displaying affinity for topoIIα with an IC50 of 2 μM and for topoIIβ with an IC50 of 120 μM. It demonstrates activity against human cancer cell lines including melanoma (A375: 12.6 μM, G-361: 8.1 μM), breast (MCF7: 15.8 μM), endometrial (HeLa: 38.2 μM), lung (A549: 17.1 μM), and prostate (DU145: 11.5 μM) cancer cells. Following a single intraperitoneal injection of 10 mg/kg, ARN-21934 achieves a peak plasma concentration of 0.68 μg/mL in 15 minutes, with a half-life of 149 minutes, and remains detectable in plasma and the brain for up to 360 minutes. [1] Jose Antonio Ortega, et al. Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β. J Med Chem. 2020 Nov 12;63(21):12873-12886.

Idarubicin, a potent anthracycline antileukemic agent, is orally active in its application. It functions by inhibiting topoisomerase II, thus interfering with DNA replication and RNA transcription. Furthermore, Idarubicin induces DNA damage, inhibits DNA synthesis, and suppresses c-myc expression. It also demonstrates inhibitory effects on the growth of bacteria and yeasts [1] [2] [3] [4] [5].

Topoisomerase I inhibitor 2 (ZML-8) is a highly selective DNA topoisomerase I (Top1) inhibitor that impedes Top1 activity, causing DNA damage. It arrests the cell cycle at the G2/M phase and induces apoptosis, exhibiting anti-tumor effects [1].

Topoisomerase I (Compound ZML-14) inhibitor 3 induces HepG2 cell apoptosis and arrests cell cycle at G2/M phase. Topoisomerase I inhibitor 3 is an inhibitor of topoisomerase I that interact with topoisomerase I-DNA complex [1].

Topoisomerase II inhibitor 6 (Compound 5), a tryptanthrin derivative, is a potent and selective topoisomerase II inhibitor that blocks the CCRF-CEM cell cycle in the G2 phase and induces DNA double-strand breaks (DSB). It exhibits antiproliferative activity on various tumor cell lines and has potential for cancer research [1].