Piroxantrone is one of a series of compounds commonly known as anthrapyrazoles developed in an effort to combine the broad antitumor activity of the anthracyclines with decreased myocardial toxicity. The mechanism of action of piroxantrone and other anthrapyrazoles is incompletely understood but likely involves DNA binding with induction of DNA strand breaks, DNA-protein cross-linking, and inhibition of DNA, RNA, and protein synthesis. Collectively, these findings suggested an interaction with topoisomerase II. Piroxantrone demonstrated antitumor activity in a wide spectrum of experimental systems against breast carcinoma, colon carcinoma, sarcoma, melanoma and leukemia. Piroxantrone is inactive in patients with persistent, progressive, or recurrent ovarian cancer who recently had received a platinum-based regimen. Piroxantrone has detectable but minimal activity against disseminated malignant melanoma. A phase II clinical trial of the piroxantrone administration for the treatment of advanced metastatic or recurrent endometrial cancer was prematurely terminated due to lack of patient accrual.

GALARUBICIN (DA-125) is an anthracycline derivative with anticancer activity, containing fluorine. The mechanism of action of this drug lies in inhibition of nucleic acid synthesis through intercalation with DNA. Because the structure and DNA-intercalating properties of DA-125 are similar to adriamycin, the cytotoxic effects of the two anthracyclines probably have similar biochemical mechanisms. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than adriamycin. In a rodent study, administration of D-125 in higher dose levels (25 to 50 mg/kg) has been shown to result in testicular damage.

Ametantrone (AM) is a synthetic 9,10-anthracenedione bearing two (hydroxyethylamino)ethylamino residues at positions 1 and 4; along with other anthraquinones and anthracyclines, it shares a polycyclic intercalating moiety and charged side chains that stabilize DNA binding. Ametantrone is anticancer drug candidate targeting DNA. Ametantrone is a topoisomerase II inhibitor of the anthrapyrazole family. Ametantrone induces interstrand DNA cross-links in HeLa S3 cells. These cross-links were observed only in cellular system suggesting that metabolism of the drugs is a necessary step leading to DNA cross-linking. Ametantrone appeared to be very well tolerated and easy to handle. A dose-schedule of 135 mg/m2 q 2–3 weeks was recommended for phase II studies in solid tumors.

Talisomycin (former trivial name: tallysomycin A), a third generation bleomycin analog that was studied as an antitumor antibiotic. The drug cleaved DNA preferentially at G-C and G-T sequences and produced specific cleavages at G-A sequences. Talisomycin participated in phase II clinical trial for the treatment of cancer; however, the further development of the drug was discontinued.

Ethidium is a DNA intercalating agent first discovered as and used as a veterenary trypanocide. A bromide salt is commonly used as a fluorescent tag in molecular biology. The fluorescene of ethidium bromide increased 21 fold upon binding to double-stranded RNA, 25 fold upon binding double stranded DNA. Because of the binding to DNA, ethidium bromide is a powerful inhibitor of DNA polymerase.

KRN-5500, a spicamycin derivative, is a nucleoside-like antibiotic with a broad spectrum of antitumor activity against human cancer cell lines. It also may have value in the treatment of neuropathic pain.

LADIRUBICIN is an idarubicin derivative with potential antineoplastic activity. Its primary effect is a DNA alkylation with sequence specificity similar to that of conventional nitrogen mustards. It possesses a wide spectrum antitumor activity against rapidly proliferating murine leukemias and on slowly growing transplantable human tumor xenografts.

Rebeccamycin analog (RA, Becatecarin/ BMS 181176, rebeccamycin derivative, NSC 655649) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. The mechanism of action of becatecarin is not exactly known, but it is thought that by inhibiting (blocking) the function of topoisomerase enzymes, it will destroy cancer cells and slow down the growth of the tumour. On 25 July 2006, orphan designation (EU/3/06/388) was granted by the European Commission to Helsinn Birex Pharmaceuticals Ltd, Ireland, for becatecarin for the treatment of cancers of the biliary tree.

Iododoxorubicin is an anthracycline derivative patented by Farmitalia Carlo Erba S.p.A. for cancer treatment. In preclinical studies, Iododoxorubicin has demonstrated significantly reduced levels of cardiotoxicity compared to anthracyclines. Unfortunately, during phase II clinical trials Iododoxorubicin failed to demonstrate efficacy in an advanced breast cancer patient

Pinafide is a rodenticide and anti-protozoal agent. Pinafide shows strong cytostatic activity against both HeLa and KB cells and is moderately toxic to both mice and rats. It has been proved active against experimental tumors and shown to be inhibitor of two DNA viruses. Pinafide blocks cell growth by inhibiting DNA and RNA synthesis. It has been shown to bind to double-helical DNA by intercalation. Pinafide inhibited the activity of M. tuberculosis NAD⁺-dependent DNA ligase A at concentrations of 50 uM. At the chemical screening was found that pinafide inhibited B-Myb transcriptional activity in luciferase assays. The cross placental-barrier studies showed that 3H-pinafide was present in the 14-day fetuses.