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

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• of thiazolidinedione were used to study the cytotoxic activity in comparison with camptothecin and etoposide on Jurkat, K562, HEK293, HELA, A549 and U937 cell lines. Compounds 20 and 17 showed the highest activity (IC50 = 0.29 and 0.36 nM, respectively) for leukemic monocytic lymphoma cells (U937

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

• Pedro H. P. R. Carvalho,
• Jose R. Correa,
• Karen L. R. Paiva,
• Daniel F. S. Machado,
• Jackson D. Scholten and
• Brenno A. D. Neto

Beilstein J. Org. Chem. 2019, 15, 2644–2654, doi:10.3762/bjoc.15.257

• effects and the concentrations to use the probe without causing any harm to the cells (Figure 5). Only at concentrations up to 100 μM cytotoxic effects were noted and at 10 μM no effect was observed for the designed BTD-4APTEG. For the subsequent bioimaging experiments, the fluorophore was tested at 1 μM

• , that is at a concentration 100-fold lower than that of the cytotoxic effect. The new compound was then tested as bioimaging probe in live and fixed cells (Figure 6). As can be seen, the green fluorescent dye BTD-4APTEG was found most concentrated at the plasma membranes of the MCF-7 cells in both, live

• MTT analysis after 24 h treatment with the developed dye BTD-4APTEG. No statistically significant cytotoxic effect was observed after 24 h incubation with the new dye BTD-4APTEG at 10 μM. However, the dye induced strong cytotoxic effects in all tested cell lines at 100 µM (p < 0.05). MCF-7 cells

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• activity observed for 2, 3, 6 and 8. Compounds 2, 5, 8, 9 and 10 exhibited low levels of cytotoxicity against the four mammalian cell lines tested, while 3, 6 and 7 were considerably more cytotoxic. Notably, 4 showed strong activity against the mouse myeloma NS-1 cell line, but no activity against the

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• affecting its growth, at very low concentrations, namely 10 μM, and were not cytotoxic to human fibroblasts at the same concentration. Due to the well-known relationship of the α-hemolysins expression with the accessory gene regulator (agr) of the S. aureus, we can suggest that these two peptidomimetics may

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

• 11b has been studied since it was the most cytotoxic among all. FITC (fluorescein-5-isothiocyanate)–annexin V/PI flow cytometry of HepG2 cells On HeLa cells, the efficacy of 11b was measured through the application of other apoptotic parameters like phosphatidylserine (PS) externalization, a known

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• family was widened by molecules isolated from other marine organisms, like sponges, sea whips and the brown algae of this genus Dictyota [70]. Two modifications would transform 3,7,18-dolabellatriene (12, Scheme 3) into a potent cytotoxic molecule with activity towards murine leukemia cells or human non

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• ring-closure reaction was fully reversible by irradiation with longer wavelengths. This offers the possibility of reversible switching a DAE only with visible, avoiding harmful (cytotoxic) UV irradiation. In view of the forthcoming solubilizing strategies applicable to fluorescent DAEs and intended for

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• antibiotics (e.g., cephalosporins), immunosuppressants (e.g., mycophenolic acid) and immunomodulators (e.g., fingolimod), as well as cholesterol lowering agents (statins). Generally, fungal metabolites were shown to have antiviral, cytotoxic, antineoplastic, cardiovascular, anti-inflammatory, immune

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• structurally diverse (poly)cyclic core skeletons [3][12]. A set of post-modification enzymes can transform core sesquiterpene skeletons into different kinds of sesquiterpenoids with potential anticancer, cytotoxic and antibiotic functions [13]. More than 121 skeleton structures derived from the sesquiterpene

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• ], helminthosporol (7) [15], bipolenin A (8) [3], secolongifolene diol (9) [15], dihydroprehelminthosporol (10) [1] and sorokinianin (11) [2], and the cytotoxic sesterterpenoid, terpestacin (12) [16][17] (Figure 1). Bipolenin K (1) was isolated as a colourless oil. Its molecular formula was determined as C15H22O3

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• . Interestingly, we found that neither archangelolide nor its dansyl conjugate did exhibit cytotoxic effects in contrast to the structurally closely related counterparts trilobolide and thapsigargin. We explain this observation by a molecular dynamics simulation, in which, in contrast to trilobolide

• ] and was also found to be cytotoxic with localization to the endoplasmic reticulum [8]. The cytotoxicity of compound 2 prompted the preparation and evaluation of compound 2 conjugates with porphyrins [9] and steroids [10] for targeted uptake of compound 2 into cancer cells, and the conjugates showed

• with compound 1 and its derivatives up to a final concentration of 50 µM for periods of 24, 48 and 72 h. Surprisingly, compound 1 exhibited almost no cytotoxic effect under these conditions (see Supporting Information File 1, Table S2 and Table S3, Figures S21–S23). The IC50 values were in the upper

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• . A compound which was found to be predominantly produced under iron deficiency was subsequently isolated. Its structural characterization by spectroscopic and bioinformatic analyses revealed a previously not known diastereomer of the cytotoxic alkaloid agrochelin. The structure of this natural

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• substitution pattern at the phenyl moiety (Figure 2A). The small library of compounds enabled a better understanding of the structural factors determining the antiviral activity versus the cytotoxic one, with the major effect found for substituents at the para-position [23]. Eventually, this work allowed the

• design of new compounds with antiviral activity and reduced cytotoxic effects by changing the type and position of the substituent. Such small structural changes could be implemented in a rapid manner because of the easy setup of the MCR approach. To get a deeper insight into the biological effect of Ugi

• conjugation [62][63]. Cytotoxic spirostan saponins were chosen as model compounds for the preparation of Ugi-derived analogues, such as 55 and 56 suitable for biological evaluation [62]. Besides the glucose unit, other trisaccharidic moieties (e.g., β-chacotrioside) could also be conjugated to functionalized

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• synthesis, we tentatively conclude a 2S,3R,8S,9R absolute configuration for pasteurestin C (4). The systematic name for 4 is (4S,4aR,7aS,7bR)-4-hydroxy-6,6,7b-trimethyl-2,4,4a,5,6,7,7a,7b-octahydro-1H-cyclobuta[e]indene-3-carboxylic acid. Bovistol A (1) showed weak cytotoxic effects (IC50 for L929 = 15 µg

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• cytotoxic agent. The problem of concomitant toxicity to healthy cells has been circumvented by attaching a short peptide (His-Ser-Ser-Lys-Leu-Gln-Leu) to a tether at TG’s C-8 position (1b). This modification renders the inhibitor inactive [3]. Prostate cancer cells produce on their surface the serine