Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• formulation approaches for targeting the colon through oral administration. In our previous studies, oral chemotherapy for colon tumors was aimed and promising results were obtained with formulation development studies, mucin interaction, mucus penetration, cytotoxicity, and permeability in 2D cell culture

• mathematically by release kinetic modeling for the first time. The overall findings indicated that the strategy of orally targeting anticancer drugs such as CPT with positively charged poly-β-CD-C6 nanoparticles to colon tumors for local and/or systemic efficacy is a promising approach. Keywords: colorectal

• intestinal microflora and dextrans are broken down by the endodextranases in the colon. Since they can predominantly be degraded by colonic microflora, CDs have been investigated in terms of drug delivery systems targeting the colon for many years [9][23][24]. Amphiphilic CD nanocarriers have been

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• potential uses can be either for oral delivery targeting intestine [33] or for an anti-skin cancer treatment [35], for example. This complexation step is also interesting for the synthesis of molecular imprinted polymers containing cyclodextrin [36]. In previous works, we have produced crosslinked

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• enzymatic coupling to complete the sugar nucleotide [7][8]. With this capability in place, we wished to explore the synthesis of further tools, targeting the active site cysteine residue (Figure 1c). We envisaged that access to C6–amino or C6–sulfhydryl species of type 8 would offer prospect to establish

• accepted. Evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose suggests that the ligand can bind to GMD, but that targeting inhibitive S-alkylation of an sp3-hybridised C6 electrophilic probe is ineffective here. a) Proposed oxidative pathway for provision of GDP-ManA 5 from GDP-Man 1, C6 stereochemistry of 3 is

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• the prediction of the producer of natural products with the functional groups of interest, leading to a higher rate of hits. We recently exploited genome mining targeting hydrazine synthetase and the generation of inorganic hydrazine N2H4 in acid hydrolysate as an indicator of N–N bond-containing

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• ). The deletion mutant was constructed by λ-RED-mediated PCR targeting mutagenesis method [27]. The positive cosmid pSC-21A4 was transformed into E. coli BW25113/pIJ790 for gene inactivation. Then, the PCR fragment was introduced via electro-transformation into E. coli BW25113/pIJ790-pSC-21A4, in which

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• inductive heating technology has also been used in multistep processes targeting drugs or important molecules in the fragrance industry. The first example deals with a metal-free carbon–carbon-bond formation process between tosylhydrazones generated from the corresponding aldehydes 74 and boronic acids 76

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• targeting of cancer cells, resulting in low bioavailability and systemic side effects [6]. To address these drawbacks, various approaches have been developed to improve the bioavailability of these and other drugs and to enable their targeted delivery to cancer cells [7][8][9][10]. In recent years

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• neuroprotective effects [6]. As part of a continuing study of our group targeting at the identification of bioactive natural products from the medicinal plants and endophytes [7][8], the chemical constituents of the stems and roots of W. nutans were investigated. This work resulted into the isolation and

The role of chemistry in the success of oligonucleotides as therapeutics

• Pawan Kumar and
• Tom Brown

Beilstein J. Org. Chem. 2022, 18, 197–199, doi:10.3762/bjoc.18.22

• nucleotides; siRNAs; RNA-targeting oligonucleotides (e.g., antisense, siRNA, and anti-miR) are widely explored as fundamental research tools and are gaining increasing promise as therapeutic agents, particularly against diseases of genetic origin. The idea of treating a disease by targeting the molecular

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• , such as intracellular phase transition [22], molecular imaging [23][24][25][26][27][28][29][30][31][32][33], anisotropic hydrogels [34][35], targeting subcellular organelles [36][37][38][39][40], elimination of pluripotent stem cells (PSC) [41][42], and cancer therapy [43][44][45][46][47][48][49][50

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• designed and prepared [3], with the hope of developing more efficient anticancer drugs with either improved Cdk targeting or with a different mechanism of action [4][5]. The isomers B and D (Figure 1) are synthetic derivatives of paullones, in which either the lactam unit is shifted (B) or both the lactam

• to isomer C and a number of closely related derivatives with modified electronic and steric properties, e.g., bromo-substituted species, backbone with 8-membered azocinone ring, will trigger the design and synthesis of new exciting anticancer drug candidates, including metal-based, by targeting

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• continuity. While targeting to discover antiviral agents [35][36][37], particularly the class of dideoxynucleotides, it is essential to investigate possible fundamental alteration of the furanose ring and the practical and convenient synthesis of these analogues. These investigations are needed to improve

• was devised for targeting specific receptors on the leukocytes membrane. The crucial N-glycosylation reaction between 1,3-oxathiolane precursor 45 and silylated cytosine was carried out using TiCl4 as a catalyst. The N-acylation of compound 92a was performed for flash chromatography, and further

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• material could be a potential for targeting release in the colon. 4. Other cryogel applications For cryogel biomedical applications not discussed in section 5, including cell separation, tissue engineering scaffolds, bioreactors and capturing of target molecules, the reader is directed to a recent review

• ) functionality [97]. The cryogels were synthesised by photochemical crosslinking of N,N-dimethylacrylamide (DMA) and β-CD triacrylate (Figure 7) and aripiprazole was incorporated through inclusion inside the hydrophobic β-CD domains. The release of aripiprazole was monitored at pH 1.2 and 6.8, targeting oral

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• methacrylate) (pPEGMA) and the anticancer drug PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsenonous acid) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and PENAO were reported. Both PISA particles were reacted with triphenylphosphonium (TPP) as mitochondria targeting units in order to

• cells. When TPP was conjugated to the pMPC PISA particles more cellular uptake as well as better spheroid penetration were observed, while TPP on PEG-based PISA had only little effect. It was hypothesized that TPP on the micelle surface may not be accessible enough to allow mitochondria targeting, but

• more structural investigations are required to elucidate this. Keywords: micelle; mitochondria; phosphorylcholine; PISA; polymerization-induced self-assembly; Introduction Targeting mitochondria is a promising strategy for the development of new anticancer drugs [1]. Among them, organoarsenical drugs

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• targeting of the small receptor molecule and, thus, reducing the need for complexity compared to enzymes or co-factors. Conversely, a multitude of geometries may need to be considered for anions with linear, coplanar, trigonal or tetrahedral topologies (Figure 1b) [5][10]. However, following the advances in

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• . The key features of ASOs further enable them to be transformed into personalized medicines, eventually even targeting patient-specific sequences and very rare diseases [1]. ASOs can mediate gene silencing via different mechanisms of action. ASOs that induce RNase H degradation of the endogenous RNA

• improved liver targeting [22][23] and ASO–glucagon-like peptide-1 (GLP1) conjugation for improved delivery to pancreatic β-cells [24]. Previously, Menzi et al. reviewed the impact of cationic modifications and conjugations for ONs and siRNAs biophysical and biological activities until 2015 [25]. In this

• to a Watson–Crick interacting ON, both targeting the same ssDNA) exhibited the ability to invade double-stranded DNA (dsDNA) targets in vitro [56]. The functionalization with aminoalkyl variants onto the nucleobase is not limited to the C-5 position on the pyrimidine base. Another important site is

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• . fumigatus as an example because of its high medical importance and its diverse profile of secondary metabolites which seems to fulfil dual roles: targeting innate immune cells during virulence and protect from environmental predators in natural habitats. Review Natural products of Aspergillus fumigatus The

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• , which drives the epithelial to mesenchymal transition [35]. Kruppel-like factor 5 (KLF5) is commonly upregulated in several cancer types and promotes pancreatic cancer proliferation by targeting the cell cycle [36]. MECOM (also known as PRDM3) is a nuclear TF known to ablate inflammatory responses and

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• cells [72]. GPNA targeting the transcriptional start-site of the human E-cadherin gene had potent and sequence-specific antisense activity and was less toxic to the cells than the PNA–polyarginine conjugate [73]. Interestingly, the α-arginine modification in either ʟ- or ᴅ-configuration destabilized PNA

• oligonucleotides at neutral pH [100][101][102]. Rozners and co-workers were the first to introduce M in triplex-forming PNAs targeting dsRNA [28]. Having a pKa of ≈6.7, M is partially protonated at physiological pH 7.4, which facilitates fast binding and formation of strong triplex [28][30][31]. While all

• bonding options on the purine base as well. An extended nucleobase S (Figure 7) originally developed for triplex-forming oligonucleotides [114][115], was introduced in PNAs targeting U interruptions in polypurine tracts of dsRNA triplexes [111]. However, in PNA, S showed limited sequence specificity

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• was hybridized with a DNA target. The double-headed nucleoside 41 has potential in DNA invader probes as well as in RNA targeting and detection [23]. 1,3-Furanosyl double-headed nucleosides In this section, all double-headed nucleosides with furanosyl ring structures are collected. The first

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• apoptosis [1][2][3][4][5][6][7]. Due to its involvement in a wide range of cellular processes, significant efforts have been made in the last two decades targeting sphingosine analogues signalling as a therapeutic strategy. For instance, FTY720-P (3), the phosphate of FTY720 (2, fingolimod), proved to be a

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• ]. In combination with the high selectivity for RNA sequences, this makes LNA-modified oligonucleotides well suited for use as antisense therapeutics. Recent publications have used LNA’s high affinity for RNA sequences in gapmer-designed antisense oligonucleotides for successful targeting of a key gene