intercalation

BMH-21, a small molecule DNA intercalator, binds ribosomal DNA and inhibits RNA polymerase I (Pol I) transcription and not affects phosphorylation of H2AX.

UNBS3157 is a novel naphthalimide derivative that is non-hematotoxic and exhibits significant antitumor activity through DNA intercalation and the poisoning of topoisomerase IIalpha. Unlike Amonafide, a related naphthalimide compound that showed activity in Phase II breast cancer trials but did not proceed to Phase III due to dose-limiting myelotoxicity, UNBS3157 has a maximum tolerated dose 3-4 times higher and does not cause hematotoxicity in mice at effective antitumor doses. In vivo models, including (i) L1210 mouse leukemia, (ii) MXT-HI mouse mammary adenocarcinoma, and (iii) human A549 non-small cell lung carcinoma and BxPC3 pancreatic cancer orthotopic models, demonstrate superior efficacy of UNBS3157 compared to Amonafide.

MitoNeoD is a novel mitochondria-targeted O2(⋅−) probe that can be used in vivo. It prevents DNA intercalation. MitoNeoD incorporates a carbon-deuterium bond, and enhances O2(⋅−) selectivity.

YO-Pro 1, a cyanine dye consisting of benzoxazole and quinoline rings connected by a linker, is almost nonfluorescent in water, but its fluorescence is greatly enhanced after intercalation in double-stranded DNA, forming the basis of DNA concentration assays. Ex/Em (bound DNA) = 491/509 nm. YO-Pro 1 can be used to identify apoptotic cells.

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.

Amikhellin HCl, an antimitotic drug, is a synthetic water-soluble derivative of khellin, an alkaloid extracted from seeds of Ammi Visnaga. Amikhellin has been used so far mostly as a vasodiator. Amikhellin binds to double-stranded DNA by an intercalation process. It inhibits the DNA-polymerase from murine sarcoma leukemia virus.

Cyclopentenylcytosine (CPC), a nucleoside analog, effectively inhibits CTP synthetase, leading to reduced levels of cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in leukemic cells. Furthermore, it enhances the phosphorylation of 1-β-D-arabinorubosylmannosylcytidine (araC) and increases its DNA intercalation activity. In the human T lymphocyte line MOLT-3, cyclopentenylcytosine triggers apoptosis and necrosis in a dose (50-300 nM) and time (8-16 h) dependent manner. When used in conjunction with araC, cyclopentenylcytosine augments the induction of both apoptosis and necrosis, amplifying its cytotoxic effects on T lymphoblasts.