DNA Binding Compounds. VI. Synthesis and Characterization of 2,5'-Disubstituted Bibenzimidazoles Related to the DNA Minor Groove Binder Hoechst-33258

Abstract

A series of compounds have been synthesized in which the basic 2-phenylbibenzimidazole structure of Hoechst 33258 has been modified to include various combinations of bromo, iodo, methoxy, amino, alkylamino and nitro groups in the terminal phenyl ring. Both sequential and convergent synthetic routes have been followed using coupling reactions of both imino ethers and aldehydes to 1,2-diamines. All these compounds were characterized by a combination of f.a.b. mass spectrometry and 'H and 13C n.m.r. spectroscopy including inverse detection of long-range heteronuclear CH correlations (HMBC).

Boron-Containing Polyamines as DNA Targeting Agents for Neutron Capture Therapy of Brain Tumors: Synthesis and Biological Evaluation

“…This uptake is comparable to that of the clinically used compounds, BSH and BPA, but at a media concentration that is 100−1000-fold less. Accordingly, carboranyl polyamines possess advantages as potential BNCT agents when compared to other boronated compounds such as amino acids, − nucleosides/nucleotides, − and other potential DNA-targeting structures. ,, The high hydrophilic properties of these polyamine salts allow for their direct administration at suitable concentration levels in water. No cosolvents such as DMSO or various alcohols are necessary.…”

“…A key question is how can tumor cells be selectively targeted? There has been a concerted effort to synthesize a variety of boron-containing analogues of biologically active compounds such as amino acids, − peptides, nucleosides/nucleotides, − and porphyrins − as well as DNA binders. ,− Such structures might function in a manner similar to their naturally occurring counterparts and become selectively incorporated into either proliferating or more metabolically active tumor cells. Another potential class of compounds are the polyamines, including putrescine, spermidine (SPD), and spermine (SPM) (Figure ), which are essential for cell growth and differentiation, especially in rapidly proliferating cells. , Polyamine depletion has growth inhibitory effects. , This has been the basis for the preparation of various polyamine synthetase inhibitors , and synthetic polyamines for cancer treatment.…”

In Vitro Studies with Methylproamine

“…Methylproamine was synthesized according to the general procedures described previously (10,11). The details are available as supplementary data.…”

Synthesis and Biological Evaluation of Boron-Containing Polyamines as Potential Agents for Neutron Capture Therapy of Brain Tumors

“…The basis for their preparation is that such structures might function in a manner similar to their naturally occurring counterparts and become selectively incorporated into either proliferating or more metabolically active tumor cells. Boron-containing analogues of porphyrins − and DNA binders − have been also considered as potential agents for BNCT.…”