23491-49-8Relevant academic research and scientific papers
Di-(benzimidazole)-1, 2, 3-triazole derivative as well as preparation and application thereof in inflammatory dermatosis
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Paragraph 0058-0060; 0084-0086, (2021/06/23)
The invention belongs to the technical field of drug small molecules, and particularly discloses a brand-new di-(benzimidazole)-1, 2, 3-triazole derivative as well as preparation and application of the brand-new di-(benzimidazole)-1, 2, 3-triazole derivative. The research finds that the brand new compound has an excellent drug effect and low toxic and side effects on the aspect of inflammatory dermatosis, and has a good application prospect in the aspect of drug development of the inflammatory dermatosis.
Hoechst-naphthalimide dyad with dual emissions as specific and ratiometric sensor for nucleus DNA damage
Yang, Fu,Wang, Chao,Wang, Lu,Ye, Zhi-Wei,Song, Xin-Bo,Xiao, Yi
supporting information, p. 2019 - 2022 (2017/10/10)
A ratiometric fluorescent sensor (Hoe-NI) was developed by connecting a nucleus targeted Hoechst unit to a naphthalimide dye via “click chemistry”. The sensor achieves high specific nucleus labeling with wash-free staining method in various kinds of living cells. The fluorescence ratio of the two emission bands (450 nm for Hoechst and 505 nm for naphthalimide) is changed sensitively to the variation of DNA concentrations, which provides the quantitative information in the processes of DNA damage induced by hydroxyl radicals and antitumor drug. Therefore, Hoe-NI is a recommendable sensor for the monitoring of nuclear DNA damage that reveals the health status of cells.
Design and synthesis of new benzimidazole-carbazole conjugates for the stabilization of human telomeric DNA, telomerase inhibition, and their selective action on cancer cells
Maji, Basudeb,Kumar, Krishan,Kaulage, Mangesh,Muniyappa,Bhattacharya, Santanu
supporting information, p. 6973 - 6988 (2014/10/16)
Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC 50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.
RADIOPROTECTOR COMPOUNDS AND METHODS
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Page/Page column 48-49, (2011/10/31)
The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula (II), as follows: wherein W represents -N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, -NHN(R1R2), NHR3N(R1R2), -NHR3OR2, -N(R3)R3OR2, -N(R1)R3OR3OR3, OR3NR1R2, -OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, -N(CO)N(R1R2), -N(CO)OR1, -N(CO)OR3OH, -(CO)NR1R2, -R3(CO)NR1R2, -R3OR1, -OR1, -N(R1R2) OR -NH-; R1 and R2 are the or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; group or chain; Z is the same or different and represents N or CH; Z' is the same or different and represents N or C; X represents CH, N or NH, where .. is a double bond when X is CH or N and a single bond when X is NH; X' represents N or NH, wherein when X is CH or N X' is NH and wherein X and X' are different and further where ～～～is a double bond when X' is N and a single bond when X' is NH; Q represents H, alkoxyl, -NR1R2, F or Cl; Q1 is absent when Z' is N and when Z' is C it represents H, alkoxyl, -NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.
Radioprotectors
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Page/Page column 20, (2009/04/23)
A compound of the formula (Ib): wherein X is NCH3, Y is N, Z is N, R3 is N(CH3)2, and (a) R1 is CH3, R2, R4 and R5 to R11 are hydrogen or (b) R5 is CH3 and R1, R2, R4 and R6 to R11 are hydrogen, and salts and tautomers thereof.
RADIOPROTECTOR COMPOUNDS AND RELATED METHODS
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Page/Page column 41-42, (2008/12/06)
The invention relates to radioprotectors of formula (I), processes for their preparation and their use in protecting biological materials from radiation damage. In diagnostic and therapeutic radiology, particularly in cancer radiotherapy, the radioprotectors of the present invention may be used to protect certain normal tissues or structures from radiation damage. The radioprotectors of formula (I) may also have uses in decreasing the effects of irradiation in non-medical scenarios, both civil and military.
OLIGOHETEROAROMATIC LUMINISCENT ASSEMBLIES AS HIGH-AFFINITY DNA SEQUENCE-DIRECTED LIGANDS
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Page/Page column 50; 95, (2010/11/27)
The present invention provides a novel class of oligoheteroaromatic assemblies with luminescence characteristics and composition based on integrated polyheterocyclic polyamide oligomers of multiple nitrogen-containing heteroaromatic of the general formula (I) This novel class of compounds of the present invention is capable of binding to targeted DNA sequence in the minor groove, and thus is useful for genomics applications. In particular, the compounds of the invention binds to the DNA at a binding stoichiometry of 2: 1 ternary complexation with very high affinity and sequence selectivity.
A PROCESS FOR THE SYNTHESIS OF BISBENZIMIDAZOLES AND ITS DERIVATIONS
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Page 10, (2008/06/13)
A process for the synthesis of bisbenzimidazoles and its derivations comprising; (i) reacting 5 chloroaniline with zinc dust and acetic anhydride to produce 5 chloroacetanilide; (ii) reacting 5 chloroacetanilide with HN03 to produce 2-nitro-5-chloroacetanilide; (ix) adding sodium methoxide to 2-nitro-5-ch1oroaniline; (x) heating 2-nitro-5-chloroaniline, methyl piperazine, anhydrous K2CO3 and Dimethyl formamide at 100-120°C produce a mixture which is cooled by pouring ice and is filtered to obtain 5-(4'-methylpiperazin-1'-yl)-2-nitroaniline; (xi) treating 5-(4'-methylpiperazin-l'yl)-2-nitroaniline with Pd/C to produce 2-amino-4-(4'-methylpiperazin-1'-yl) aniline; (xii) refluxing a mixture of 2-amino-4-(4'-methylpiperazin-1'yl) aniline and ethyl-4-amino-3-nitrobenzenecarboximidate hydrochloride in presence of ethanol/glacial acetic acid to produce 4-[5'-(4"-methylpiperazin-1"-yl) 15 benzimidazol-2'-yl)-2-nitroaniline; (xiii) treating a solution of 4-[5'-(4"-methylpiperazin-1"-yi) benzimidazol-2'-yl)-2-nitroaniline with palladium on carbon to yield 2-amino-4-[5'-(4"-Methylpiperazin-1"-yl)benzimidazol-2'-yl]aniline; (xiv) heating 2-amino-4-[5'-(4"-Methylpiperazin-1"-yl)benzimidazol-2'-yl]aniline and 3-4-dimethoxy benzaldehyde using nitrobenzene as a solvent at 110-150°C to produce (DMA) i.e 5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl] benzimidazole; (ix) heating 2-amino-4-[5'-(4"-Methylpiperazin-1"-yl) benzimidazol-2'-YI] aniline and 5-Formyl-[3-methoxy-4-hydroxy benzimidazole] using nitrobenzene at 110°C to 150°C in presence of argon to produce (TBZ) i.e 5-(4-methylpiperazine-1-yl)-2-[2' (2"-(4-hydroxy-3methoxyphenyl)5"benzimidazolyl) -5'- benzimidazolyl] benzimidazole.
Influence of phenyl ring disubstitution on bisbenzimidazole and terbenzimidazole cytotoxicity: Synthesis and biological evaluation as radioprotectors
Tawar, Urmila,Jain, Akash K.,Dwarakanath,Chandra, Ramesh,Singh, Yogendra,Chaudhury,Khaitan, Divya,Tandon, Vibha
, p. 3785 - 3792 (2007/10/03)
DNA minor groove binders, Hoechst 33258 and Hoechst 33342, have been reported to protect against radiation-induced DNA-strand breakage, but their mutagenicity and cytotoxicity limit their use as protectors of normal tissue during radiotherapy and as biological radioprotectors during accidental radiation exposure. On the basis of these observations, two new nontoxic disubstituted benzimidazoles were synthesized, one having two methoxy groups (5-(4-methylpiperazin-1-yl)-2-[2′-(3,4-dimethoxyphenyl) -5′-benzimidazolyl]benzimidazole, 5) and another having a methoxy and a hydroxyl group (5-(4-methylpiperazin-1-yl)-2-[2′{2″-(4-hydroxy-3-methoxyphenyl) -5″-benzimidazolyl}-5′-benzimidazolyl]benzimidazole, 6) ortho to each other on the phenyl ring. The radiomodifying effects of these nontoxic ligands were investigated with a human glioma cell line exposed to low linear energy transfer radiation by determining cell survival and cell proliferation compared with effects of the parent compound, Hoechst 33342. Cytotoxicity assayed by analyzing clonogenicity, cell growth, and metabolic Viability showed that both 5 and 6 were nontoxic at 100 μM after 72 h of exposure, whereas Hoechst 33342 resulted in lysis of 77% of these cells in 24 h. Macrocolony assay (clonogenicity) showed that 73%, 92%, and 10% of the cells survived when treated with 100 μM 5, 6, and Hoechst 33342, respectively. Both 5 and 6 did not affect the growth of BMG-1 cells. At 10 μM, 5 and 6 showed 82% and 37% protection against radiation-induced cell death (macrocolony assay) while 100% protection was observed against growth inhibition. Disubstitution of the phenyl ring has not only reduced cytotoxicity but also enhanced DNA-ligand stability, conferring high degree of radioprotection.
DNA binding compounds. VII synthesis, characterization and DNA binding capacity of 1,2-dicarba-closo-dodecaborane bibenzimidazoles related to the DNA minor groove binder Hoechst 33258
Bateman, Stuart A.,Kelly, David P.,Martin, Roger F.,White, Jonathan M.
, p. 291 - 301 (2007/10/03)
A series of bibenzimidazole derivatives based on the known DNA minor groove binder Hoechst 33258 have been prepared to include a 1,2-dicarba-closo-dodecaborane cage for potential use in boron neutron capture therapy (BNCT). The carborane derivatives (5)-(7) were chosen to reduce the steric inhibition of minor groove DNA binding displayed by the previously prepared carborane ligand (4). The synthesis and preliminary DNA binding studies of these bibenzimidazole derivatives are presented herein.
