First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• cytotoxicity compared to hoshinoamide B. Herein, we report the initial progress on the total synthesis of hoshinomaide A. The key challenges for the total synthesis of hoshinoamide A are the coupling of highly methylated amino acids and the purification of hydrophobic peptides. Results and Discussion As shown

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• even under harsh conditions (temperatures up to 100 °C in dichloroethane and use of H2SO4 as acid), and the starting material was recovered in all of the reactions. Selected final compounds 5 and intermediates 9, 12, 13, and 17 obtained in this work were tested for their cytotoxicity. We conducted

• standardized MTT assays [41] to evaluate if the newly accessible compounds of type 5 and their precursors could become interesting target molecules for biological investigations or if the compounds show high toxicity, which might prevent their use. We monitored cytotoxicity at six different concentrations

• effects at high concentrations. Interestingly, no common structural motif promoted an increase in the in vitro cytotoxicity. However, by comparing the IC50 values of the compound classes 12 and 13, regioisomerism seems to play a decisive role: while compounds 12a and 12d–h had no influence on the

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

• , ʟ-nucleosides are typically endowed with lower host toxicity [11][12]. The antiviral activity and cytotoxicity in MT-4 cells showed that racemic (±)-BCH-189 (1c) possesses lower anti-HIV activity (ID50 = 0.37–1.31 µM) than AZT (ᴅ-nucleoside, ID50 = 0.0048–0.0217 µM). However, (±)-BCH-189 (1c

• nucleoside 97 (Scheme 42). Unfortunately, the introduction of a tetrazole ring to the oxathiolane moiety did not result in any anti-HIV activity and higher cytotoxicity. The synthesis of N4-substituted analogue 99 of 2',3'-dideoxy-3'-thiacytosine was discovered by Camplo et al. (Scheme 43) [77]. The prodrug

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• above-mentioned potential of a nitrogen-containing steroids, and as a continuation of our research in the field of bile acids and steroidal heterocycles, in this work, we aimed to prepare a series of new bile acid tetrazoles with potential cytotoxicity towards selected tumor cells. To achieve the

• linear dose dependence of cytotoxicity through the tested concentration range (Figure 4A). Compound 3 also showed strong activity on the HeLa cell line. Introduction of tetrazole ring instead of ketone diminished activity toward the MDA-MB-231 cell line in compound 13 (IC50 > 100 μM). The same trend with

• activity toward the HeLa cell line (IC50 = 6.97 μM), while tetrazole 22 showed strong and selective activity toward the HT-29 cell line (IC50 = 6.06 µM). Compounds 7, 23, and 24, which showed strong cytotoxicity to the breast cancer cell line MDA-MB-231 (in addition to compound 3), also exhibited a

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

• interactions between anionic sulphate groups and the primary amine group present in doxorubicin which confers a positive charge under physiological conditions. This interaction was confirmed by in silico modelling. While the carriers did not show any cytotoxicity, cell viability was reduced in the presence of

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -dihydro-α-pyrone derivatives, bearing either a distinctive cyclopropane or furan ring and named brevipolides A–O (1–15), have been isolated from the invasive plant Hyptis brevipes Poit. Their fascinating structural features, and the potent biological activities, including cytotoxicity against an array of

• , C5’S, and C6’S. Most brevipolide members exhibited cytotoxicity against various targets, including human colon, breast, laryngeal, cervix, prostate, and nasopharyngeal cancer cell lines with ED50 and IC50 values ranged in micromolar order [1][4][12]. One member showed activity in an enzyme-based

• -brevipolide H. Kumaraswamy and co-workers also performed a bioassay study for compounds 41 and 43 and found a higher cytotoxicity for the latter derivative against the MFC-7 cancer cell line. Hou’s strategy to ent-brevipolide H (ent-8) Hou and co-workers, in 2014, demonstrated an efficient approach to

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• , respectively, only compound 8 showed a significant activity (96.2 ± 1.1% for 3). The other compounds exhibited moderate or no NGF secretion effect. The cytotoxicity of compounds 1–19 was also evaluated against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) through an SRB assay. All the

• were expressed as a percentage of the control group (untreated cells). Cytotoxicity assessment. The SRB assay was performed to evaluate cytotoxicity of all the isolated compounds against four cultured human cancer cell lines. The cell lines (National Cancer Institute, Bethesda, MD, USA) were used A549

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

• proliferation of human synovial sarcoma SW982 cells (Figure 7). All four PISA particles displayed an enhanced cytotoxicity compared to free PENAO using SW982. While PENAO’s cytotoxicity arises mainly from crosslinking two cysteine loops in the mitochondrial ANT protein, the here employed systems seem to not

• than a 2-fold decrease in cytotoxicity, thus being less toxic compared to PPM-NP4 micelle, while MPM-NP2-TPP displays slightly lower IC50 values than that of MPM-NP2 (Figure 7). This is in agreement with the uptake results as PPM-NP4-TPP displays lower uptake while MPM-NP2-TPP displays higher uptake

• surfaces only enhanced tumor penetration and cytotoxicity for the zwitterionic micelles, while no positive effect was seen for the PEGylated micelles. More importantly, no increased mitochondria targeting ability was observed for both micelles. While the attachment of TPP clearly influenced the biological

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• cytotoxicity against P388 murine leukemia cells with IC50 values of 33 and 89 μM, respectively. Keywords: Actinomadura; nomimicin; polyketide; spirotetronate; Introduction Actinomycetes are a valuable source of bioactive compounds, accounting for approximately two thirds of all known antibiotics, and more

• 2 exhibited cytotoxicity against P388 murine leukemia cells with IC50 of 33 and 89 μM, respectively. Conclusion In summary, UV-based chemical screening of bioactive compounds from marine-derived actinomycetes led to the discovery of three new polyketides, nomimicins B (1), C (2), and D (3) along

• tautomer are included in Supporting Information File 1. Biological assays Antimicrobial activity and cytotoxicity were evaluated according to the procedures previously described [29]. Structures of nomimicins A–D (4 and 1–3). COSY and key HMBC correlations for 1. Relative configuration of 1 determined by

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

• derivative group, when conjugated to the C-5 position on 2’-deoxyuridine (Table 1B, 12), improved antisense activity while reducing toxicity [39]. In addition, a 15-mer PS-ASO, modified with the C-5 tris-aminated 2’-deoxyuridine 12, improved anti-HIV activity and reduced cytotoxicity relative to the

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

• breast cancer cells by arresting the cell cycle and promoting apoptosis while showing no cytotoxicity against RAW 264.7 cells, thus demonstrating their selectivity [65][67]. Further, fumigaclavine was shown to exhibit antibacterial properties and to contribute to virulence in the model insect Galleria

• . fumigatus was driven by its pathobiology, e.g., a role in cytotoxicity, immunosuppression or antifungal drug resistance. In natural habitats these molecules may fulfill analogous functions, such as the defense against phagocytic predators by gliotoxin [78][79][80][81][82]. Indeed, the need for survival is

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

• (Figure 5). In addition to retaining the superior nucleic acid binding (due to preorganization of PNA’s backbone) miniPEG greatly improves aqueous solubility of PNA without causing any cytotoxicity [89]. Because of the superior binding properties, miniPEG-modified PNAs can invade any sequence of dsDNA

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• cancer cells. Keywords: γ-carboline; cascade reaction; cell uptake; cytotoxicity; fluorescence; Introduction Carbolines are privileged aza-heterocycles found in the core of several natural and synthetic compounds and are known for their biological applications. Among the four different isomers, 9H

• shown promising biological activities in preclinical and clinical studies (Figure 1) [2][3][4][5][6]. The pyrimidine-γ-carboline alkaloid ingenine B (isolated from an Indonesian sponge) exhibits a pronounced cytotoxicity against a murine lymphoma cell line [7] and several isocanthine analogs are

• with a standard drug, doxorubicin, were screened for their cytotoxicity against various cancer lines (Figure 5, Table 3 and Figure S2, in Supporting Information File 1) such as MCF-7 (breast cancer), HeLa (cervical cancer), HEK293 (human embryonic kidney cells), A431 (skin cancer), A549 (lung cancer

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• metabolites exhibited very weak cytotoxic effects at the highest concentration, only 2, 4, and 6 displayed mild cytotoxicity, allowing for a determination of IC50 values, which ranged from 9.5–32 µg/mL. To our surprise, fulvoferruginin (1) displayed greater cytotoxic effects than previously reported (though

• for other cell lines) [8], which led us to assess its cytotoxicity further against different carcinoma cell lines. The IC50 values of compound 1 range from 0.06–0.7 µg/mL for all tested cell lines (Table S2 in Supporting Information File 1). Discussion The lack of bioactivity for metabolites 2–6 can

• be attributed to an absence of the α-methylene lactone unit present in fulvoferruginin (1). Nevertheless, the cytotoxicity detected here for fulvoferruginin shows that re-evaluating the bioactivity of previously isolated basidiomycete metabolites in different bioassays can lead to unexpected results

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• , it has been found that berberine (1a) exhibits a selective cytotoxicity against cancer cells [12][13], which is mainly based on its DNA-binding properties [14]. Since the complexation with DNA leads to significant changes of the fluorescent quantum yields of the bound berberine, it can also be used

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• average sizes of 57.3 nm and 91.9 nm, respectively, as well as a more negative ZP (−11 mV and −9.4 mV, respectively, Table 2). These ZP values indicate that complexation leads from a neutral to anionic LNP product [39], a property that typically confers with low to no cytotoxicity in vivo [40]. Further

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• properties of selected aminophthalazinones towards Cu(II) ions were investigated and the participation of the nitrogen atoms in the complexation of the metal ion was shown. A biological screening of the potential cytotoxicity of selected synthesized compounds on HT-29 and PC-3 cell lines, as well as on the L

• -929 cell line, proved that some amino derivatives of phthalazinone show interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays are reported. Keywords: amination; complexes; cytotoxicity; Pd cross-coupling; phthalazinone; Introduction Phthalazine and its

• platinum disc electrode suggested that the [(L3)Cu(II)Cl2]/[(L3)Cu(I)Cl2] redox couple was formed. For more details, see Supporting Information File 2. Bioactivity Cytotoxicity analysis – MTT assay We used the MTT assay to evaluate compounds 5c, 5d, 5f, 5g, 6b, and 6d for their potential activity on

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• effects including cytotoxicity against cancer cell lines, antineuroinflammatory activity, and potential neurotrophic effect were evaluated. Keywords: antineuroinflammation; Chaenomeles sinensis; cytotoxicity; megastigmane; neurotrophic effect; Introduction Chaenomeles sinensis (Thouin) Koehne (Rosaceae

• compounds 1–12 were evaluated for their cytotoxicity against four human tumor cell lines, antineuroinflammatory activity using lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cell lines, and potential neurotrophic effects in C6 cells. Results and Discussion From the n-BuOH-soluble fraction of the

• continuing search for cytotoxic, antineuroinflammatory, and neurotrophic secondary metabolites from C. sinensis [13][14][15][21], the isolates (1–12) were tested for these biological activities. The cytotoxicity was evaluated on the basis of the growth inhibitory effects of the isolated compounds 1–12

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• intensity. Control studies confirmed that the tailor-made GCP moiety is crucial for selective recognition of 14-3-3 proteins. A high cell viability is observed for these two probes when tested with HeLa cell lines in cytotoxicity studies. β-Tryptase β-Tryptase is the predominant secretory granule-derived

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

• several human cancer cells, but has only a relatively low cytotoxicity in healthy cells [31][32]. Berberine is also known as a G4-DNA ligand [33]. Especially berberine derivatives that carry additional substituents with varying alkyl chain lengths in the 9- and 13-position show enhanced binding properties

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• understanding of the structure–cytotoxicity relationship [14]. Therefore, we were motivated to develop a new synthetic methodology for N-alkyl and N-phenyl derivatives 4 and 5 starting from 2 with 1. Results and Discussion Our studies began with an exploration of a promising substrate for the desired

• bearing an acrylamide side chain as a common intermediate. Finally, we subjected methylene-lactone-fused spirolactams to the assay of cytotoxicity on P388 cells (Figure 2). N-Methyl-substituted spirolactam 5c exhibited potent cytotoxicity (IC50 0.32 μg/mL) which was comparable to that of the N-acetyl

• analog E (0.16 μg/mL) [14]. It should be noted that the IC50 values of our recently reported non-conjugated lactone F [27] was >100 μg/mL. In addition to 5c, we tested the cytotoxicity of methylene-lactam-based compound 4o, which exhibited weak activity (IC50 12.4 μg/mL) against the P388 cell line. These

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• 1 and 4 exhibited weak cytotoxicity against P388 murine leukemia cells, with an IC50 of 38 and 33 μM, respectively. Conclusion Alkanoylimidazoles, 4-acylated imidazoles of varying chain length and terminal branching, with occasional substitution at C-5 by an amino group, are an emerging class of

• 13.5 min), nocarimidazole B (4, 8.0 mg, tR 17.3 min) from fraction 4, and bulbimidazole A (5, 3.2 mg, tR 11.2 min) from fraction 5. Bioassays The antimicrobial activity was evaluated in a similar manner as previously reported [22]. The cytotoxicity against P388 murine leukemia cells was examined

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• concentrations, exhibit the same morphological appearances, agreeing with the statement that the nanofibers likely are made of Nap-ffky. Cytotoxicity, cell lysates, and protein delivery We investigated the cell compatibility of 1 and 2 by incubation with two kinds of mammalian cells, HeLa and Saos-2 cells, using

Host–guest interaction of cucurbit[8]uril with oroxin A and its effect on the properties of oroxin A

• Zhishu Zeng,
• Jun Xie,
• Guangyan Luo,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 2332–2337, doi:10.3762/bjoc.16.194

• involve three main intermolecular forces: a hydrophobic effect, hydrogen bonding and ion–dipole interactions at the carbonyl portals [7][8][9]. The high thermal stability [10], ease of synthesis [11], general absence of cytotoxicity or toxicity [12][13] and their good molecular recognition and binding