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

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

• studies show that the γ-carbolines are highly toxic to cancer cells at micromolar concentrations similar to doxorubicin, whereas they are non-cytotoxic (Figure 6) to human macrophages or immune cells. At last, to evaluate cell uptake of the novel γ-carboline for fluorescence imaging, live-cell imaging

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

• antibiotic fulvoferruginin (1), fulvoferruginins B–F (2–6). The structures of these sesquiterpenoids were elucidated using HRESIMS, 1D and 2D NMR, as well as CD spectroscopy. Assessing the bioactivity, fulvoferruginin emerged as a potent cytotoxic agent of potential pharmaceutical interest. Keywords

• 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

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• marketed drugs structured around indole implying its pharmacological significance such as oxypertine (27), ateviridine (28) [47] and spirooxindole-based potent cytotoxic agents 29, 30 and 31 [48]. In 2017, Lin and co-workers [49] designed a TFA-catalyzed three-component reaction for the regioselective

• reaction time of 24 h. A scale protocol adapted with same reaction conditions afforded the product with a better yield of 92% supporting the scale-up strategy with microwaves. The protocol provided an easy admittance to 5-aza-7-deazapurine molecules used as antiviral and cytotoxic agents [101]. The

• , antiulcer, anxiolytic, antiherpes agents [115][116][117][118][119]. Similarly, pyrazolo-pyridines are found to be potent antibacterial (131), cytotoxic (132), antiproliferative (133) and antimalarial (134) agents (Figure 10) [120][121]. 8.2.1 Imidazo[1,2-a]pyridine: Sun and co-workers [122] accomplished the

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• Pseudopterogorgia americana in 1972 (Figure 1B) [7], several others from the family have been reported [8][9][10][11][12][13][14]. The 9,11-secosterols exhibit diverse biological activities, including antihistaminic, antiproliferative, anti-inflammatory, cytotoxic and protein kinase C (PKC) inhibition activities [8

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

• cytotoxic activity of amino- and polyaminophthalazinone derivatives. Results and Discussion Chemistry Synthesis of aminophthalazinones The synthetic route toward the aminophthalazinones 5 and 6 is shown in Scheme 1 (route B). A current literature review [19][34] and our experience [35] proved, that the

• cytotoxicity, proliferation and growth of HT-29 (human colon adenocarcinoma cell line), PC-3 (human prostate cancer cell line) and L-929 cells (mouse fibroblast cell line). The results obtained from the MTT assay revealed that the tested phthalazinone derivatives were cytotoxic towards the tested cell lines in

• the concentration range from 20.1 μM to 92.93 μM (Figure 6 and Figure 7). The compounds 5d, 5g and 5f exhibited the strongest cytotoxic effects as compared to the other examined compounds. The IC50 values for the tested cell lines were respectively: HT-29 (IC50 = 29.79 µM; 31.45 µM; 27.41 µM), PC-3

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• cytotoxic against a variety of cancer cell lines, and both bohemamine and NP25302 inhibit HL-60 cell adhesion to Chinese hamster ovary cells expressing intercellular adhesion molecule ICAM-1 (CD-54). This interest led us to develop a total synthesis of NP25302 [25] and its 5-normethyl analog and, as

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

• [14], lignans [15], and oxylipins [21] with cytotoxic, anti-inflammatory, or potential neuroprotective activities. In order to search for minor constituents of other structure classes in C. sinensis twigs, the MeOH extract and the four solvent-partitioned fractions were further investigated to afford

• 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

• ) exhibited mild growth inhibitory effects against A549 and BT549 cell lines with IC50 values of 27.1 and 22.7 μM, respectively (Table 2). Betulinic acid (10) is a well-known anticancer agent inhibiting eukaryotic topoisomerase I [36] and its derivatives have been reported to display cytotoxic activity [13

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• 4 binds with dsDNA in a combined intercalation and minor groove binding mode, whereas probe 5 binds with the outer surface of dsDNA. These two probes are low cytotoxic and probe 4 has been successfully used for imaging of nuclear DNA (Figure 5B, inset). Protein detection Specific peptides and

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• imidazo[1,5-a]pyridine core is also considered to be one of the privileged pharmacophoric scaffolds and can be found in many biologically active compounds, for example, the potent antitumor agent C 1311 inhibiting topoisomerase II [4][5][6][7][8][9] or pirmagrel, a cytotoxic immunosuppressant and DNA

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

• -lactone derivatives spiro-fused to an oxindole (A), one of which exhibited a potent cytotoxic activity [9]. Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a

• key reaction (Scheme 1b) [10][11]. More recently, an amide-functionalized allyl boronate was developed as an alternative reagent for the allylstannane [12][13][14][15][16], which led to the syntheses of not only cytotoxic methylene-lactones spiro-fused to a lactam ring (B) but also their analogous

• results suggest that cytotoxic activity of this type of spirolactams against P388 cells is simply related to the methylene lactone structure [28]. Conclusion In conclusion, we have achieved a new bifurcated syntheses of N-alkyl and N-phenyl-substituted spirolactams bearing a methylene-lactone or methylene

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• ], tau aggression [3], and heat shock protein 90 [4], in addition to their antimicrobial, cytotoxic, anticancer, and anti-inflammatory effects [5]. To date, over 400 azaphilones have been reported from various fungal strains, the majority of which have been produced by ascomycetes belonging to the

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• William A. Donaldson Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881, USA 10.3762/bjoc.16.166 Abstract The spliceostatins/thailanstatins are a family of linear peptides/polyketides that inhibit pre-mRNA splicing, and as such act as potent cytotoxic

• human spliceosome, splicing factor 3b [6], which inhibits pre-mRNA splicing, and as such act as potent cytotoxic compounds. A review of the discovery, target identification, and biological applications of the compounds that exhibit these binding characteristics has been published [7]. These compounds

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• tuberculosis H37Ra at IC90 6.8 μM while weakly cytotoxic to MRC-5 human lung-derived fibroblasts with GI50 84.7 μM [30]. It did not inhibit the production of nitric oxide in RAW 264.7 murine macrophage-like cells [31]. In our hands, 1 was inactive against any of the tested strains including Staphylococcus

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• Figure 6, 2f also exhibited cytotoxicity against U251 human glioblastoma cells and HKBMM human malignant meningioma cells. Importantly, the diselenide 2f was more cytotoxic toward HeLa cancer cells than to human brain microvascular endothelial (HBME) cells, which are noncancerous (Figure 7). Hence, the

• diselenide 2f may possibly be highly cytotoxic toward various cancer cell lines and relatively low cytotoxic against noncancer cells. Conclusion The Cu-catalyzed double C–H selenations of imidazo[1,2-a]pyridines with Se powder afforded novel bis(2-arylimidazopyridin-3-yl) diselenides in satisfactory yields

• yield is given. The cytotoxic effect of the bis(2-arylimidazo[1,2-a]pyridin-3-yl) diselenides 2 and selenides 3 on human cervical cancer HeLa cells. HeLa cells were exposed with or without each compound at 25 µM for 24 h. The cell viability of HeLa cells was confirmed by MTT assays. The data are

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• cytotoxic anthraquinone moiety and obtained positive, yet limited, cytotoxic activities [63][64]. Furthermore, a steroidal anti-estrogen–doxorubicin conjugate was synthesized by Hanson, showing a 70-fold increase of activity compared to doxorubicin in inhibiting cell proliferation and promoting cell death

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• constitute a broad family of natural macrolides that act as powerful cytotoxic agents against various cancer cell lines. Due to the stereochemical intricacy and high cytotoxicity, these compounds have attracted a great deal of attention from synthetic chemists. The application of an intermolecular enyne

• , thereby affording the triene intermediate in a substantial yield. Additional transformations using conventional methods efficiently provided (−)-amphidinolide E (3). Amphidinolide K, another important bioactive macrolide endowed with specific cytotoxic activity against L1210 and KB cancer cells, was also

•  11). This innovative methodology allowed the installation of the vicinal exo‐methylene branches characteristic for the cytotoxic marine natural product amphidinolide V as well as the determination of its absolute configuration. It further enabled the synthesis of a set of diastereomers and analogs of

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• exhibit a wide range of biological activities, including antibiotic [8], antiviral [9], antifungal [10], phytotoxic [11], cytotoxic [12][13], and enzyme inhibitory activities against bacterial DNA-directed RNA polymerase [14]. The wide range of biological activity and structural variation of this class of

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• be cytotoxic against human leukaemia, kidney, ovarian and prostate cancer cell lines (IC50 = 25 µM, U251 cell line) [14][15][16]. In an attempt to increase the bioavailability of (R)-(+)-goniothalamin 2, aza-goniothalamin 1 was designed and synthesised; however, aza-goniothalamin 1 was found to have

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• developed HTI-based antimitotics with cytotoxic potencies in the low micromolar range (Figure 1a) [18]. In this work, we wished to enhance the bioactivity of the distinctive dark-active HTI-based tubulin-binding antimitotics while retaining the benefits of the HTI scaffold, namely robust, fatigue-resistant

• (Figure 1a). Indanocine is a cytotoxic indanone-based CDI (EC50 ≈ 10–40 nM) [22] with similar cell culture potency to colchicine (EC50 ≈ 3–20 nM) [23] that likewise disrupts MTs, arrests cells in the G2/M phase, and induces apoptosis. Although the size and geometry of thioindoxyl and indanone rings differ

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• [51], are excluded from the legislation governing animal testing, i.e., experiments do not require ethical approval. In this study, we selected 19 photoswitchable DAE-modified cytotoxic peptides from our previous SAR evaluation [30] and established with them the D. rerio embryotoxicity assay. For each

• photoswitchable peptides explored in this study. (A) The reversible photoisomerization of the dithienylethene photoswitch core. (B) Photoconversion between ring-open and ring-closed photoforms of DAE-derived peptides. (C) Structures of the non-photoswitchable cytotoxic peptide GS (1), and one of our first

• the ring-open photoforms (B, open circles). The compound numbers are shown next to the data points, and the color code is the same as in Figure 3. Phototherapeutic cytotoxic action against HeLa cells of GS 1 and its photoswitchable analogues 2–20, correlated with the new in vivo results and earlier in

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• possess nonselective activities in biological systems and exhibit antimicrobial [28], cytotoxic [29], antimycobacterial [30], and antimalarial [31] effects. Pigmentosin A (1) and its new derivative pigmentosin B (2) exhibited weak activity against B. subtilis, with MIC values of 12.5 and 100 μg/mL

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• myxobacterium Archangium gephyra (Figure 1) [5][6]. These cyclic peptides have interesting biological activities such as cytotoxic activity presumably via proteasome inhibition and immunomodulatory effects, and they also show good antibiotic effects against P. aeruginosa [7][8][9]. The structure–activity

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• isolated and characterized five previously undescribed secondary metabolites, skeletocutins M–Q (1–5), along with the known metabolite tyromycin A (6) from the fruiting bodies of the polypore Skeletocutis sp. The new compounds did not exhibit any antimicrobial, cytotoxic, or nematicidal activities. However

• antimicrobial, cytotoxic, and nematicidal activities, as described in the Experimental section. However, compounds 1–5 were devoid of activity in these assays, whereas tyromycin A (6) and skeletocutin A–L had been reported before to be active against several Gram-positive bacteria [4], namely Bacillus subtilis