Polyfunctional DNA intercalating agents

Sequence‐Selective Intercalation of Antitumour Bis‐Naphthalimides into DNA

“…The bridge selected to connect the naphthalimide rings was chosen on the basis that it should contain at least one chargeable amine group, shown to be an essential sidechain element for significant cytotoxic activity in the naphthalimide series (Brafia et al, 1981), and that it should be long enough to enable both chromophores to intercalate. These criteria appeared best fitted by connecting the imide ring nitrogens with a polyamine-like -(CH,),-NH-(CH,),-NH-(CH,),-linker which would be at once flexible, effectively mimic the side chain present in active mononaphthalimides, and span a distance which comfortably permits bis-intercalation in the acridine series (Wright et al, 1980;Wakelin and Waring, 1990). To determine whether the bis-naphthalimide LU 79553 does indeed bis-intercalate into DNA we investigated its effects on the viscosity of closed circular duplex pUC12 DNA, which provides a sensitive measure of the drug-induced unwinding of the double helix required by the intercalation hypothesis (Waring, 1970).…”

Novel bis-phenanthridine derivatives with easily tunable linkers, study of their interactions with DNA and screening of antiproliferative activity

“…The advantages in respect to commonly used synthesis [11,12,15] were demonstrated by easy and efficient modulation of bis-phenanthridine structure starting from the only two building blocks (glycine and phenanthridine-L-alanine), which allowed simple tuning of the cavity size between phenanthridine subunits as well as intramolecular rigidity of compounds. Spectrophotometric studies revealed that in biologically relevant medium bisphenanthridine derivatives exhibit significant intramolecular interactions strongly dependent on the rigidity and length of the peptide linker.…”

“…[10] A huge number of bis-phenanthridine derivatives were prepared with the aim of not only enhanced affinity due to the bis-intercalation into DNA/RNA but also with the idea of introducing selectivity. [11] Moreover, some bis-phenanthridine compounds have shown at the time the highest binding constants for nucleotides but not selectivity among studied nucleobases. [12] Our recent results have pointed out that selectivity of bis-phenanthridine derivatives toward various DNA/RNA sequences could be controlled by the steric effects [13,14] or by electrostatic interactions with DNA/RNA backbone and/or nucleobases.…”

Phytochemical Constituents, Thin Layer Chromatography and Antimicrobial Activity of Methanol Extract of the Stem and Leave of <i>Citrus Limon (L)</i>

“…It is also estimated that 74% of the 119 currently most important drugs contain active ingredients from plants used in traditional medicine for health care [12], these traditional medicines are primarily plant-based [13]. Another study of the most prescribed drugs in the USA indicated that a majority contained either a natural product or a natural product was used in the synthesis or design of the drug [14]. Similarly, about 121 drugs prescribed in USA today come from natural sources, 90 of which come either directly or indirectly from plant sources [15].…”