Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• irradiation of the styrylpyridines and formation of the intercalator directly in the presence of DNA. In addition to the DNA-binding properties, the tested benzo[c]quinolizinium derivatives also operate as photosensitizers, which induce DNA damage at relative low concentrations and short irradiation times

• , even under anaerobic conditions. Investigations of the mechanism of the DNA damage revealed the involvement of intermediate hydroxyl radicals and C-centered radicals. Under aerobic conditions, singlet oxygen only contributes to marginal extent to the DNA damage. Keywords: DNA intercalators

• also the ability to induce DNA damage upon irradiation [35][36][37][38], and may therefore be considered as promising basis for the development of new reagents for photodynamic (chemo)therapy (PDT). Notably, PDT has developed into an important therapeutic tool against several serious diseases, such as

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• , in the suppression of gene expression [11][12] or the induction of the cellular response to DNA damage [13][14]. Because of the increasing evidence of an essential biological function of G4-DNA, this DNA form is considered as an attractive target in drug development [1][2][15][16]. For that purpose

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent

• . A variety of reaction mechanisms are initiated, which, aiming to the photocleaver, may lead to DNA damage. A requirement for nucleic acid’s and most protein’s “transparency” is irradiating at wavelengths longer than 310 nm [15]. “Transparency” means lack of damage due to irradiation itself and

• , Figure 1) are also recognized as DNA “photocleavage” agents owing their action to the homolysis of their vulnerable N–O bond, at 312 nm [9][39][40][41][42][43] or 365 nm [44][45] yielding photogenerated carbonyloxyl radicals (CRs), which are able to cause oxidative DNA damage. We have recently reported

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• gel electrophoresis (Figure 7). Apoptotic hallmark of chromosomal DNA laddering was clearly evident in HeLa cells, treated with different doses of the compound as compared to untreated cells. Thus these two assays comet formation and DNA laddering indicated DNA damage during the apoptotic induction

• μM) (2′,7′-dichlorodihydrofluorescein diacetate) for 30 min at 37 °C as described previously [38]. Estimation of DNA damage (comet assay and DNA gel electrophoresis) Comet assay was performed on HeLa cells by single cell gel electrophoresis as reported by Liao et al. and the examination was performed

• was added per 100 mL gel solution for a final concentration of 0.5 μg/mL. Comet assays for detection of DNA damage of both control and 11b treated HeLa cells were detected by single cell gel electrophoresis. We isolated DNA of HeLa cells by a standardized salting out method according to Miller et al

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• instability of the adduct under acidic conditions during ODN synthesis [7]. In recent years, applications of ODNs have extended to emerging areas such as nanotechnology [8][9], antisense drug development [10][11][12], DNA damage and repair [13][14], DNA methylation and demethylation [15][16][17][18], DNA

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• stabilized complex prevents the re-ligation step of DNA, catalyzed by topo I, resulting in DNA damage and therefore cell death (apoptosis). CPT is predominantly cytotoxic during the S phase replication of DNA because of the collision of the replication fork with the cleavable complex, converting the single

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• cellular processes without perturbing the system under study. In another report using the tCO–tCnitro FRET pair as a probe of protein interaction, Ansari et al. investigated the DNA damage repair system [82]. Here the FRET pair is used to better understand the conformational dynamics along the DNA-lesion

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• from the nucleus to the cytosol, acting as E3 ubiquitin ligase that marks p53 for degradation by the proteasome. Following DNA damage, p53 rises and becomes phosphorylated, thus translocates to nucleus where it binds DNA and activates expression of several proteins that arrest cell proliferation until

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• [2 + 2] photocycloaddition of thymine derivatives has been extensively discussed in the literature [9][10][24][25] because it is important in DNA damage (as cycloreversion is in DNA repair) [26][27]. Accordingly, the photodimerisation can occur in an anti and a syn fashion leading to regioisomeric

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• assembly of the desired chain without DNA damage. In the current study, we have chosen to couple three amino acids, which contain functional groups commonly used in SELEX approaches to modify DNA or RNA, to 5-iodo-2’-deoxyuridine. We describe the direct and linker-less introduction of histidine, serine and

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• has been attributed to their ability to form interstrand DNA cross-links. The resulting covalently linked bases block any machinery that relies on separating the strands of the DNA duplex, e.g., DNA damage repair, replication and transcription [1][2][3][4][5], which is exploited in using CENU

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• spectrometry, and elemental analyses techniques. The study of the interaction of these trisubstituted triptycenes with various forms of DNA revealed interesting dependency on the functional groups of the triptycene core to initiate damage or conformational changes in DNA. Keywords: abasic site; DNA damage

• generated when a purine (A/G) or a pyrimidine (C/T) base is stripped off from the DNA strand and this is considered as the most common type of DNA damage lesions. We generated one abasic site in a 48-base pair long oligomer duplex by treating the DNA (Figure 3) with Uracil DNA Glycosylase (UDG) enzyme

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• ; oligonucleotide synthesis; phosphotriester approach; Introduction Maintaining the integrity of the genome is of paramount biological importance, since the damage of DNA is considered to cause aging and various degenerative diseases. To prevent the pathological DNA damage, cells evolve the DNA repair machinery

• , which restores the chemical information encoded in genome. In addition to the enzymatic DNA repair system, a new and quite different repair mechanism, i.e. the non-enzymatic repair, has been discovered. This non-enzymatic system refers to the removal of transient products of the DNA damage like short

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• groove of double-stranded DNA [4][5]. While the mode of action of anthracyclines is still not fully understood, it is widely accepted that these chemotherapeutic agents form a ternary complex with double-stranded DNA and topoisomerase II thereby leading to DNA damage and cell death [6][7]. They are used

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• Scheme 15 [102][103]. The DNA damage is initiated by metabolic reduction and cyclization of 117 to N-hydroxyaristolactam 126. After loss of water, the aristolactam nitrenium ion 127, which is believed to be the main carcinogen, reacts with DNA bases such as adenosine, to give the corresponding 7

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• DNA damage, while corydine and atherospermidine also induce DNA damage [25]. Zanthoxylum is a potential source of lead compounds that can inspire the synthesis of bioactive principles based on an isoquinoline scaffold. Experimental General methods Melting points were determined on a Sanyo Gallenkamp

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• subset of α-methylenecyclopentenone-containing tetrahydro-β-carbolines was synthesized. These compounds contain a general substructure that has recently been shown to inhibit DNA damage checkpoints [8]. Allene-ynes 9{1,3}–9{1,4} undergo Pauson–Khand cyclocarbonylation reactions when treated with

Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates

• Wang-Yong Yang,
• Samantha A. Marrone,
• Nalisha Minors,
• Diego A. R. Zorio and
• Igor V. Alabugin

Beilstein J. Org. Chem. 2011, 7, 813–823, doi:10.3762/bjoc.7.93

• groups at the site of initial single-strand (ss) DNA damage and convert it into the more therapeutically important ds DNA damage [26]. We have shown that these compounds also could break intercellular DNA [27] and induce >90% cancer cell death at concentrations as low as 10 nM [25]. In spite of these

• conjugates displayed G-selective cleavage, especially at GG and GGG sites adjacent to the AT-rich sequence (the AT-tract), the preferred binding location for protonated amines. The G-selectivity is typical for oxidative DNA damage via PET for the most easily oxidized base, guanine. However, a noticeable

• amount of cleavage at a single G site in the AT-rich region is not consistent with purely oxidative DNA damage in the presence of spatially close GG and GGG sites, both of which are better sinks for the transient hole in the DNA. This observation suggests the presence of competitive DNA-cleavage