Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• apoptosis [7]. Figure 1 highlights the structures of three EGFR inhibitors approved by the United States Food and Drug Administration (FDA) and one known tubulin inhibitor: erlotinib (1), gefitinib (2), lapatinib (3), and MPC-6827 – verubulin (4) [5][7]. Given that 4-anilinoquinazolines are potential

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• after substraction of the basal value. Flow cytometry P-glycoprotein activity was assessed using the reporter dye calcein acetoxymethyl ester (AM) as described previously [59]. To assess apoptosis, VCR-R CEM cells were seeded at 0.125 × 106 cells/well, incubated for 4 h and stimulated as indicated for

• 48 h. Apoptosis was analyzed by propidium iodide staining and flow cytometry as described by Nicoletti et al. [60]. All flow cytometry experiments were conducted on a BD FACS Canto II (BD Biosciences). Prominent synthetic approaches to 1-benzyltetrahydroisoquinolines: Bischler–Napieralski, Pictet

• significance was determined by ordinary one-way ANOVA and Dunnett’s post test. ****p < 0.0001. D) Combination treatment of benzylisoquinolines and vincristine. VCR-R CEM cells were treated with 0.1 or 1 µM vincristine for 48 h in presence or absence of the respective benzylisoquinoline (10 µM). Apoptosis was

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

• , entries 1–7). A very low ED50 value of 8.5 nM was obtained for brevipolide C (3) (Table 2, entry 3) [4], making it a very potent lead compound for anticancer candidates related to mitochondrial dysfunction effect. A reduction in the mitochondrial membrane potential (MMP) could also indicate apoptosis [20

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

• ]. PENAO triggers cell apoptosis by targeting the ANT protein, which is located in the mitochondria. More specifically, PENAO binds to the thiols located on the ANT peptide loops Cys57 and Cys257, which results in the formation of stable cyclic dithioarsinite complexes [5]. Arsenic drugs do not only bind

• only rely on that reaction to introduce cell apoptosis, as all particle systems are cytotoxic regardless of reaching the mitochondria or not. The mitochondria contain indeed several vicinal protein thiols that readily react with trivalent arsenicals, however, it has been shown that various other

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• the transduction of signals; these processes induce cell apoptosis [8][9]. As mutations in the BCR-Abl-1 enzyme domain can occur, cases of resistance have emerged in the treatment with TKIs, compromising its effectiveness [10][11]. In continuation of the work by our group to develop new imatinib

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

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

• regulatory circuits and access chromatin despite it being in a condensed state [3]. These TFs act as “master regulators”, promoting the expression of several genes across many signaling pathways, such as differentiation, apoptosis, and cell proliferation. The precise targets of the TFs are controlled by

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

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• then to subsequent ceramide-linked glycoconjugate acceptors, before transport and eventual incorporation into the plasma membrane via vesicular fusion. Gangliosides, which function as antigenic determinants [4], may play a role in membrane organization [5], cell signaling [6], apoptosis [7], and in

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• , tau, theta, sigma, and zeta) [43][44]. This protein family plays key roles in human physiology including metabolism, stress response, protein trafficking, cell-cycle control, signal transduction, apoptosis, and neurotransmission by binding to their phosphorylated protein partners [45]. They are

• (Figure 10C). Lysosomes tracking Lysosomes participate multiple roles including intracellular transportation, metabolism, cell membrane recycling, and apoptosis [60]. Lysosomal lumen is acidic in nature and it is required for lysosomal enzyme activities. Deviation of lysosomal functions could result in

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• protein were used to segment whole cells and mitochondria, respectively (blue and yellow areas, Figure 7a). The structural characteristics of the cells were extracted from both masks. Possible damaged cells with early signs of apoptosis or abnormal mitochondrial networks were excluded (Figure 7a, right

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• hydrazone derivatives enhances the apoptosis inducing activity [54]. Another particularly useful feature of the hydrazone group is related by its high tendency to provide solid derivatives. The target of the here reported strategy is to recover as pure products the desired functionalized DHBERs to evaluate

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

A smart deoxyribozyme-based fluorescent sensor for in vitro detection of androgen receptor mRNA

• Ekaterina A. Bryushkova,
• Erik R. Gandalipov and
• Julia V. Nuzhina

Beilstein J. Org. Chem. 2020, 16, 1135–1141, doi:10.3762/bjoc.16.100

• transcription factor [8]. Among the target genes of the AR are genes encoding proteins involved in intracellular signal transmission, proliferation, as well as differentiation and apoptosis [9]. An increase of AR mRNA expression or enhancing their sensitivity to the corresponding ligands may lead to the

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• taxonomically related strains also produce similar sets of fabclavines (Table 2) [26]. In addition to the high homology between the xlt and fcl BGCs, our results strongly suggest that Xlt and the fabclavines are identical. The bioactivity described for Xlt relies on the induction of epithelial cell apoptosis in

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• differentiation, cell cycle progression and apoptosis by targeting both histone and non-histone proteins. The balance between acetylation and deacetylation is pivotal for typical cell function. Abnormal or increased HDAC expression has been reported in several human tumors and cancer cell lines [2]. As such, the

• classified as highly potent amongst traditional HDACis [11]. According to previous reports, panobinostat not only induces apoptosis in cells, but also stimulates cell growth inhibition, and cell-cycle arrest in a time- and dose-dependent manner. Thus, panobinostat has demonstrated high therapeutic potential

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• eggplant calyx induces apoptosis in human ovarian cancer cells, leading to cell death [33]. One example of a keto fatty acid from the animal kingdom is (E)-9-oxo-2-decenoic acid, a sex pheromone found in royal jelly. Queen honey bees use this fatty acid to control the activity of worker bees [34]. (E)-7

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

• (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

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• , anti-allergic, antispasmodic, diuretic and anticancer [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. For example, baicalein can play an antitumor effect on lung cancer by inducing cell apoptosis, blocking cell cycle and inhibiting metastasis of lung cancer, but it

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

• spirothiazolidinediones via a [2 + 2 + 2] cyclotrimerization reaction and the derivatives were further functionalized through DA chemistry and click reaction. Using flow cytometry, it was shown for the first time that the new benzyl alcohol derivatives of thiazolidine-2,4-dione generated here are efficient apoptosis

• inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell lines. Keywords: apoptosis; biologically active; [2 + 2 + 2] cycloaddition; flow cytometry; spiro thiazolidinedione; Introduction Heterocyclic compounds play a vital role in the metabolism of all living cells. Thus, most of the biologically active

• ), and 22 was active against T-cell leukemia (Jurkat) with an IC50 value of 0.34 nM. Further, these three compounds (22, 20 and 17) were used to study apoptosis and the cell cycle in cells of the corresponding cell cultures. The highest percentage of apoptosis was observed when compound 22 was added to

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

• transduction, apoptosis and even necrosis [8][9][10]. The monitoring of plasma membranes, their biophysical properties, endocytosis/exocytosis of several types of molecules, as well as their dynamic changes, may be performed by using fluorogenic organic dyes or derivatives thereof [11][12][13][14][15]. The

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 against human and murine tumour cell lines. This suggests that the regioisomeric lactone moiety could play an important role in the observed cytotoxicity. Interestingly, 3 (SF002-96-1 [4]) was previously shown to inhibit survivin, which is a member of the inhibitor of apoptosis (IAP) family and a

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

• ], B cell lymphoma (A20 cells) [28], and head and neck squamous cell carcinoma (HNSCC cells) [29], among others. The mechanism of biological action of SAHA in different types of cells is indeed plural in nature. Some of the common cell death pathways are intrinsic and extrinsic apoptosis [30], ROS

• induce apoptosis, and to induce generation of ROS. Compounds 11b and 11f were arbitrarily chosen, while the shorter chain analogue 11g was selected to compare the effect of chain length, if any. Direct comparison with SAHA was made to quantify the effects shown by these three compounds in each of the

• sorting) The results were further complimented with ROS dependent cytotoxicity in the above cell line. ROS generation, induced by various anticancer agents plays a key role in apoptosis [37]. Cells were treated with SAHA, 11b, 11f and 11g at GI25, GI50 and GI75 concentrations for 24 h and analyzed in the

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• copper complexes have an interesting antiproliferative capacity towards a range of human cancer cell lines, inducing early apoptosis, followed by secondary necrosis [64]. The fluorescent analog having pyridine imine and PEG terminal functions shown in Scheme 7 has been synthesized with the aim of

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• [2][3][4], such as antiproliferative, antifertility [5], anti-osteoporosis [6], immunosuppressive and anti-inflammatory activities [7]. Reports have indicated that triptolide induces apoptosis, triggers autophagy [8], and arrests cell cycle progression through modulating the relevant signaling

• pathways involved in the regulation of reactive oxygen species (ROS) and/or nitric oxide (NO) [9], histone methyltransferase [10], HSP70 [11], Jak2, Bcl-2/Bax [12], caspase 8 [13], NF-κB [14], X-linked inhibitor of apoptosis protein (XIAP) [15], MAPK, PI3K [16], and MPK1, ERK-1/2, and JNK-1/2 [17]. The