120122-47-6Relevant academic research and scientific papers
Design and Synthesis of Novel Thiazole-Containing Cross-Linked Polyamides Related to the Antiviral Antibiotic Distamycin
Sharma, Sanjay K.,Tandon, Manju,Lown, J. William
, p. 1102 - 1107 (2000)
A family of naturally occurring oligopeptides includes netropsin, distamycin, anthelvencin, kikumycin B, amidinomycin, and norformycin. Netropsin (I) and distamycin (II) express their biological activities by targeting specific sequences of chemical functionalities in the minor groove of DNA. Both netropsin and distamycin can be regarded as polyamide chains in which each α-carbon has been replaced by a five-membered pyrrole ring. The repeat distance in such an augmented polyamide chain is almost the same as the distance from one base pair to the next along the floor of a minor groove within β-DNA. In this paper we report the synthesis of 16-21 cross-linked polyamides containing a thiazole heterocyclic ring bearing the active functionalites NH2, NHCHO, or H. 16 and 17 were synthesized by DCC and HOBt catalyzed reaction of 5 with 14 and 15, while the formylation products 18 and 19 were obtained by coupling the formylated 4-methyl-thiazolated acid 6 with 14 and 15. The deaminated compounds 20 and 21 were obtained by the coupling of 5-trichloroacetyl-4-methylthiazole 7 synthesized from 4-methylthiazole. All the six cross-linked polyamides 16-21 were tested for their DNA gyrase inhibition. The studies have shown these polyamides have better sequence recognition and a greater percentage of inhibition than the corresponding monomers. The compound 17 shows complete inhibition of gyrase at 0.5 μM concentration as compared to the naturally occurring distamycin at 1.0 μM.
Investigation of the factors that dictate the preferred orientation of lexitropsins in the minor groove of DNA
Alniss, Hasan Y.,Witzel, Ini-Isabeé,Semreen, Mohammad H.,Panda, Pritam Kumar,Mishra, Yogendra Kumar,Ahuja, Rajeev,Parkinson, John A.
, (2019)
Lexitropsins are small molecules that bind to the minor groove of DNA as antiparallel dimers in a specific orientation. These molecules have shown therapeutic potential in the treatment of several diseases; however, the development of these molecules to target particular genes requires revealing the factors that dictate their preferred orientation in the minor grooves, which to date have not been investigated. In this study, a distinct structure (thzC) was carefully designed as an analog of a well-characterized lexitropsin (thzA) to reveal the factors that dictate the preferred binding orientation. Comparative evaluations of the biophysical and molecular modeling results of both compounds showed that the position of the dimethylaminopropyl group and the orientation of the amide links of the ligand with respect to the 5′-3′-ends; dictate the preferred orientation of lexitropsins in the minor grooves. These findings could be useful in the design of novel lexitropsins to selectively target specific genes.
Bromoacetophenone-based photonucleases: photoinduced cleavage of DNA by 4'-bromoacetophenone-pyrrolecarboxamide conjugates.
Wender,Jeon
, p. 2117 - 2120 (1999)
[formula: see text] 4'-Bromoacetophenone derivatives which upon excitation can generate monophenyl radicals capable of hydrogen atom abstraction were investigated as photoinducible DNA cleaving agents. Pyrrolecarboxamide-conjugated 4'-bromoacetophenones were synthesized, and their DNA cleaving activities and sequence selectivities were determined.
New propylamine oligopyrrole carboxamides linked to a heterocyclic or anthraquinone system: Synthesis, DNA binding, topoisomerase I inhibition and cytotoxicity
Hotzel, Christian,Marotto, Annalisa,Pindur, Ulf
, p. 189 - 197 (2003)
Continuing our studies on combilexines, compounds consisting of a DNA intercalator linked to a minor groove ligand, new results are presented. The synthesis of a series of new propylamine oligopyrrole carboxamides closely related to netropsin and distamycin A, linked to a heterocyclic or anthraquinone system is reported. The cytotoxic activity in vitro, the DNA binding characteristics and the inhibition of the topoisomerase I of the compounds were studied in order to explain the biological mechanism of action of these new potential combilexines. Some of the synthesised compounds showed cytotoxic activity against human tumour cell lines, as well as DNA binding and topoisomerase I inhibiting properties.
Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides
Brucoli, Federico,Guzman, Juan D.,Maitra, Arundhati,James, Colin H.,Fox, Keith R.,Bhakta, Sanjib
, p. 3705 - 3711 (2015)
The alarming rise of extensively drug-resistant tuberculosis (XDR-TB) strains, compel the development of new molecules with novel modes of action to control this world health emergency. Distamycin analogues containing N-terminal biaryl-motifs 2(1-5)(1-7)
Synthesis and evaluation of novel 4-nitropyrrole-based 1,3,4-oxadiazole derivatives as antimicrobial and anti-tubercular agents
Rane, Rajesh A.,Bangalore, Pavankumar,Borhade, Sheetal D.,Khandare, Preeti K.
, p. 49 - 58 (2013)
We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based 1,3,4-oxadiazoles. The synthesized molecules were evaluated for anti-bacterial, anti-fungal and anti-tubercular activities. Promisingly, most of the compounds showed equal o
Synthesis of lipid derivatives of pyrrole polyamide and their biological activity
Yamamoto, Masahiko,Zhu, Changjin,Yi, Lui,Rong, Zheng,Miura, Yoshie,Izumi, Minoru,Nakajima, Shuhei,Tanamoto, Ken-Ichi,Shimizu, Sakayu,Baba, Naomichi
, p. 1078 - 1082 (2007)
Novel fatty acyl and phospholipid derivatives of pyrrole polyamide were synthesized. Their cytotoxicity against a cancer cell line of MT-4 cells and those infected by human immunodeficiency virus (HIV) was examined. Although no anti-HIV activity was found, their cytotoxicitty against the cancer cells was significantly enhanced by introducing a lipophilic group into the pyrrole polyamide.
4-Methyltrityl-Protected Pyrrole and Imidazole Building Blocks for Solid Phase Synthesis of DNA-Binding Polyamides
Heinrich, Benedikt,Vázquez, Olalla
supporting information, p. 533 - 536 (2020/01/31)
DNA-binding polyamides are synthetic oligomers of pyrrole/imidazole units with high specificity and affinity for double-stranded DNA. To increase their synthetic diversity, we report a mild methodology based on 4-methyltrityl (Mtt) solid phase peptide synthesis (SPPS), whose building blocks are more accessible than the standard Fmoc and Boc SPPS ones. We demonstrate the robustness of the approach by preparing and studying a hairpin with all precursors. Importantly, our strategy is orthogonal and compatible with sensitive molecules and could be readily automated.
Series of oligopolyamide containing N-methylpyrrole and N-methylimidazole and synthesis method thereof
-
Paragraph 0072; 0101-0104, (2019/10/02)
The invention discloses a series of oligopolyamide DNA minor groove ligand compounds containing N-methylpyrrole and N-methylimidazole and a synthesis method thereof. The synthesis method provided by the invention adopts a five-membered heterocyclic compound and a derivative thereof as the raw materials, and carries out a series of reactions like acylation, nitration, hydrogenation, condensation, hydrolysis and the like to synthesize the target product. The synthesis method provided by the invention is also applicable to synthesis of polyamide. The synthetic process adopted by the method provided by the invention has the characteristics of simple operation and high yield, and is suitable for industrial scale production. The oligopolyamide DNA minor groove ligand compounds containing N-methylpyrrole and N-methylimidazole provided by the invention have structural formulas shown as formula I and formula II in the specification.
Ortho -Fluoroazobenzene derivatives as DNA intercalators for photocontrol of DNA and nucleosome binding by visible light
Heinrich, Benedikt,Bouazoune, Karim,Wojcik, Matthias,Bakowsky, Udo,Vázquez, Olalla
supporting information, p. 1827 - 1833 (2019/02/20)
We report a high-affinity photoswitchable DNA binder, which displays different nucleosome-binding capacities upon visible-light irradiation. Both photochemical and DNA-recognition properties were examined by UV-Vis, HPLC, CD spectroscopy, NMR, FID assays,
