Pal, Ritesh; Chakraborty, Jeet; Mukhopadhyay, Titas Kumar; Kanungo, Ajay; Saha, Rimita; Chakraborty, Amit; Patra, Dipendu; Datta, Ayan; Dutta, Sanjay published the artcile< Substituent effect of benzyl moiety in nitroquinoxaline small molecules upon DNA binding: Cumulative destacking of DNA nucleobases leading to histone eviction>, Name: 4-Bromobenzylamine, the main research area is nitroquinoxaline preparation antitumor hydrophobicity SAR DNA binding destacking; Entropically favored; Hydrogen bond disruption; Hydrophobic interaction; In-vitro nucleosome disassembly; Mammalian cell cytotoxicity; Nucleobase destacking.
Cooperative disruption of Watson-Crick hydrogen bonds, as well as base-destacking, was shown to be triggered by a quinoxaline-based small mol. consisting of an N,N-dimethylaminopropyl tether, and a para-substituted benzyl moiety. This events led to superstructure formation and DNA condensation as evident from biophys. experiments and classical mol. dynamics simulations. The DNA superstructure formation by mono-quinoxaline derivatives I [R = 1-piperidyl, [3-(dimethylamino)propylamino]; R1 = benzyl, 2-thienylmethyl, (4-iodophenyl)methyl, etc.] was highly entropically favored and predominantly driven by hydrophobic interactions. Furthermore, oversupercoiling of DNA and base-destacking cumulatively induced histone eviction from in-vitro assembled nucleosomes at lower micromolar concentrations implicating biol. relevance. The DNA structural modulation and histone eviction capacity of the benzyl para-substituents were in the order: -I > -CF3> -Br > -Me > -OMe > -OH, which was largely guided by the polarity of benzyl para-substituent and the resulting mol. topol. The most hydrophobic derivative I [R = [3-(dimethylamino)propylamino], R1 = (4-iodophenyl)methyl] with para-iodo benzyl moiety caused maximal disruption of base pairing and generation of superstructures. Both these events gradually diminished as the polarity of the benzyl para-substituent increases. On the other hand, quinoxaline derivatives I having heterocyclic ring instead of benzyl ring, or in the absence of N,N-dimethylamino head-group, was incapable of inducing any DNA structural change and histone eviction. Further, the quinoxaline compounds I displayed potent anticancer activities against different cancer cell lines which directly correlates with the hydrophobic effects of the benzyl para-substituents. Overall, the study provided new insights into the mechanistic approach of DNA structural modulation driven histone eviction guided by the hydrophobicity of synthesized compounds leading to cellular cytotoxicity towards cancer cells.
European Journal of Medicinal Chemistry published new progress about Antitumor agents. 3959-07-7 belongs to class bromides-buliding-blocks, and the molecular formula is C7H8BrN, Name: 4-Bromobenzylamine.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary