Potentiation by phenylbisbenzimidazoles of cytotoxicity of anticancer drugs directed against topoisomerase II

Double-Stranded DNA Binding Characteristics and Subcellular Distribution of a Minor Groove Binding Diphenyl Ether Bisbenzimidazole

“…The results of our cellular investigations for H1 and H2 were fairly similar. H3 showed little cellular activity in accord with literature reports ( , ). Apparently, alkylation of the terminal phenoxy moiety of H3 imparts upon both these molecules a superior ability to traverse the cell membrane and reach its DNA target.…”

Double-Stranded DNA Binding Characteristics and Subcellular Distribution of a Minor Groove Binding Diphenyl Ether Bisbenzimidazole

“…The results of our cellular investigations for H1 and H2 were fairly similar. H3 showed little cellular activity in accord with literature reports ( , ). Apparently, alkylation of the terminal phenoxy moiety of H3 imparts upon both these molecules a superior ability to traverse the cell membrane and reach its DNA target.…”

Distamycin‐induced inhibition of homeodomain‐DNA complexes.

“…However, it has been shown that distamycin can act as a factor in the regulation of the activity to topoisomerase I (McHugh et al, 1989) and topoisomerase II (Woyonarowski et al, 1989a,b). Similar behaviour has also been demonstrated recently for the minor groove-binding ligand Hoechst 33258 (Finlay and Baguley, 1990 termini, annealed and purified on a 15% polyacrylamide gel as described (Dorn et al, 1987). The sequences of the radiolabelled double-stranded oligonucleotides used are (5'-3'): BS2-18 wt, GAGAAAAAGCCATTA-GAG; BS2-18 mut, GAGAAAAAGGGATTAGAG; BS2-18 b, GAGAAA-AAGCCCTTAGAG; …”

DNA minor groove binders as potential antitumor and antimicrobial agents

“…About the phenolic ether of Hoechst 33258, such as Hoechst 33342 (R ¼ Et, 20) or Hoechst 33377 (R ¼ Ph, 21), it has been suggested that these agents exhibit greater cytotoxicity due to their superior ability to traverse the cell membrane and reach its DNA target. 48 In fact, due to the ability of these compounds in traversing both the cytoplasmic and nuclear membranes and accumulating in the nucleus, they are capable of inhibiting the binding of regulatory proteins. 48 Lown has also synthesized a series of novel bis-benzimidazoles with general formula 22-25 incorporating benzimidazole, pyridoimidazole, and imidazoquinines moieties as one of the units of bis-benzimidazole with a piperazinyl functional group, while the other unit of bis-benzimidazole contains different leaving groups along with p-methoxy substituents.…”

“…48 In fact, due to the ability of these compounds in traversing both the cytoplasmic and nuclear membranes and accumulating in the nucleus, they are capable of inhibiting the binding of regulatory proteins. 48 Lown has also synthesized a series of novel bis-benzimidazoles with general formula 22-25 incorporating benzimidazole, pyridoimidazole, and imidazoquinines moieties as one of the units of bis-benzimidazole with a piperazinyl functional group, while the other unit of bis-benzimidazole contains different leaving groups along with p-methoxy substituents. This latter may be expected to have some influence on the nitrogen lone pair and consequently on the binding characteristics of the ligand.…”

Double-Stranded DNA Binding Characteristics and Subcellular Distribution of a Minor Groove Binding Diphenyl Ether Bisbenzimidazole

“…The results of our cellular investigations for H1 and H2 were fairly similar. H3 showed little cellular activity in accord with literature reports ( , ). Apparently, alkylation of the terminal phenoxy moiety of H3 imparts upon both these molecules a superior ability to traverse the cell membrane and reach its DNA target.…”

Distamycin‐induced inhibition of homeodomain‐DNA complexes.

“…However, it has been shown that distamycin can act as a factor in the regulation of the activity to topoisomerase I (McHugh et al, 1989) and topoisomerase II (Woyonarowski et al, 1989a,b). Similar behaviour has also been demonstrated recently for the minor groove-binding ligand Hoechst 33258 (Finlay and Baguley, 1990 termini, annealed and purified on a 15% polyacrylamide gel as described (Dorn et al, 1987). The sequences of the radiolabelled double-stranded oligonucleotides used are (5'-3'): BS2-18 wt, GAGAAAAAGCCATTA-GAG; BS2-18 mut, GAGAAAAAGGGATTAGAG; BS2-18 b, GAGAAA-AAGCCCTTAGAG; …”

DNA minor groove binders as potential antitumor and antimicrobial agents

“…About the phenolic ether of Hoechst 33258, such as Hoechst 33342 (R ¼ Et, 20) or Hoechst 33377 (R ¼ Ph, 21), it has been suggested that these agents exhibit greater cytotoxicity due to their superior ability to traverse the cell membrane and reach its DNA target. 48 In fact, due to the ability of these compounds in traversing both the cytoplasmic and nuclear membranes and accumulating in the nucleus, they are capable of inhibiting the binding of regulatory proteins. 48 Lown has also synthesized a series of novel bis-benzimidazoles with general formula 22-25 incorporating benzimidazole, pyridoimidazole, and imidazoquinines moieties as one of the units of bis-benzimidazole with a piperazinyl functional group, while the other unit of bis-benzimidazole contains different leaving groups along with p-methoxy substituents.…”

“…48 In fact, due to the ability of these compounds in traversing both the cytoplasmic and nuclear membranes and accumulating in the nucleus, they are capable of inhibiting the binding of regulatory proteins. 48 Lown has also synthesized a series of novel bis-benzimidazoles with general formula 22-25 incorporating benzimidazole, pyridoimidazole, and imidazoquinines moieties as one of the units of bis-benzimidazole with a piperazinyl functional group, while the other unit of bis-benzimidazole contains different leaving groups along with p-methoxy substituents. This latter may be expected to have some influence on the nitrogen lone pair and consequently on the binding characteristics of the ligand.…”

Double-Stranded DNA Binding Characteristics and Subcellular Distribution of a Minor Groove Binding Diphenyl Ether Bisbenzimidazole

“…The results of our cellular investigations for H1 and H2 were fairly similar. H3 showed little cellular activity in accord with literature reports ( , ). Apparently, alkylation of the terminal phenoxy moiety of H3 imparts upon both these molecules a superior ability to traverse the cell membrane and reach its DNA target.…”

Distamycin‐induced inhibition of homeodomain‐DNA complexes.

“…However, it has been shown that distamycin can act as a factor in the regulation of the activity to topoisomerase I (McHugh et al, 1989) and topoisomerase II (Woyonarowski et al, 1989a,b). Similar behaviour has also been demonstrated recently for the minor groove-binding ligand Hoechst 33258 (Finlay and Baguley, 1990 termini, annealed and purified on a 15% polyacrylamide gel as described (Dorn et al, 1987). The sequences of the radiolabelled double-stranded oligonucleotides used are (5'-3'): BS2-18 wt, GAGAAAAAGCCATTA-GAG; BS2-18 mut, GAGAAAAAGGGATTAGAG; BS2-18 b, GAGAAA-AAGCCCTTAGAG; …”

DNA minor groove binders as potential antitumor and antimicrobial agents

“…About the phenolic ether of Hoechst 33258, such as Hoechst 33342 (R ¼ Et, 20) or Hoechst 33377 (R ¼ Ph, 21), it has been suggested that these agents exhibit greater cytotoxicity due to their superior ability to traverse the cell membrane and reach its DNA target. 48 In fact, due to the ability of these compounds in traversing both the cytoplasmic and nuclear membranes and accumulating in the nucleus, they are capable of inhibiting the binding of regulatory proteins. 48 Lown has also synthesized a series of novel bis-benzimidazoles with general formula 22-25 incorporating benzimidazole, pyridoimidazole, and imidazoquinines moieties as one of the units of bis-benzimidazole with a piperazinyl functional group, while the other unit of bis-benzimidazole contains different leaving groups along with p-methoxy substituents.…”

“…48 In fact, due to the ability of these compounds in traversing both the cytoplasmic and nuclear membranes and accumulating in the nucleus, they are capable of inhibiting the binding of regulatory proteins. 48 Lown has also synthesized a series of novel bis-benzimidazoles with general formula 22-25 incorporating benzimidazole, pyridoimidazole, and imidazoquinines moieties as one of the units of bis-benzimidazole with a piperazinyl functional group, while the other unit of bis-benzimidazole contains different leaving groups along with p-methoxy substituents. This latter may be expected to have some influence on the nitrogen lone pair and consequently on the binding characteristics of the ligand.…”