Potential antitumor agents. Part 43. Synthesis and biological activity of dibasic 9-aminoacridine-4-carboxamides, a new class of antitumor agent

Abstract

The synthesis and biological activities of representatives of a new class of antitumor agent, the N-[2-(dialkylamino)ethyl ]-9-aminoacridine-4-carboxamides, are reported. Members of this class are stable and very water soluble with high levels of in vitro and in vivo antitumor activity. The compounds bind tightly to double-stranded DNA by intercalation, but the requirements for antitumor activity are more restrictive. They depend critically on the separation distance, positioning, and pKa values of the two cationic centers. For in vivo activity, significant bulk tolerance exists for lipophilic but not hydrophilic groups about the C-9 acridine position and for both lipophilic and hydrophilic groups on the side-chain cationic moiety. Significant attenuation of the pKa of the side-chain cationic center abolishes activity, as does alteration of either the disposition or separation distance of the side-chain charge with respect to the chromophore.

Copper (II) Complexes of New Carboxyamide Ligands: Synthesis, Spectroscopic and Antibacterial study

“…Knowledge of the structure of amides and also of the amino acids, provided by the theory of resonance and verified by extensive careful experimental studies made by R. B. Corey and his coworkers, has been of much value in the determination of the structure of the amide complexes. It is known that the amide groups to retain their planarity, the atoms are expected not to deviate from the planar configuration by more than perhaps 0.05 Å.Amide group being the repeating unit of the biologically important polypeptide macromolecules, it has attracted the attention of the chemists to synthesize the coordination compounds of transition metal ions with the ligands containing amide and to study the structure, antifungal, antibacterial and physiological activity of the ligands and their metal complexes [3][4][5][6] .…”

Considerations for Treatment Development in Rhabdomyosarcoma: In Vitro Assessment of Novel DNA Binding Drugs

“…In doing so it was our intention to identify agents with the potential to expand treatment options for RMS patients and further improve the efficacy of chemotherapy protocols that utilize general cytotoxic agents. Each of the novel compounds assessed in this study contain tricyclic carboxamide moieties that act as DNA intercalating chromophores and have previously been shown to be cytotoxic in leukaemia and/or solid tumour cell lines (Wakelin et al, 2003;Baguley et al, 1995;Atwell et al, 1984). One group of novel transcription inhibitors ( Figure 1A) contain dual intercalating chromophores that are joined via their 9-amino groups by linker chains of various structures and contain N,N-dimethylaminoethyl (DMAE) active side chains.…”

Synthesis of Novel Eu(III) Luminescent Probe Based on 9- Acridinecarboxylic Acid Skelton for Sensing of ds-DNA

“…A number of techniques have been employed to study the interaction of drugs with DNA [3][4][5][6][7][8], including fluorescence spectroscopy [9], UVspectrophotometry [10], electrophoresis [11], nuclear magnetic resonance [12], and electrochemical methods [13]. In recent years, there is a growing interest in the absorption and fluorescence investigations of interactions between anticancer drugs and other DNA targeted molecules and DNA [14][15][16]. UV-vis absorption and fluorescence spectroscopy are regarded as effective methods among these techniques because they are sensitive, rapid and simple [17].…”