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

• , the 4-methoxyphenyl group appeared to enhance the anticancer activity of the bis(2-arylimidazo[1,2-a]pyridin-3-yl) diselenides and selenides. Furthermore, only the compound 2f showed a higher anticancer activity than doxorubicin (DOX), a well-known anthracycline-based anticancer drug. As shown in

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• affinity and specificity for system L [58]. Accordingly, 2-[18F]FELP 95 emerged as a promising PET radiotracer for brain tumor imaging [97][98][99][100][101] (Figure 2). 5.2. Incorporation of FPhe for the synthesis of fluorinated drugs 5.2.1. Melflufen, an anticancer drug: 4-Fluoro-ʟ-phenylalanine ester is

• required for the synthesis of melflufen (179), an anticancer drug currently being in clinical trials for the treatment of relapsed and refractory multiple myeloma (RRMM) [102][103]. Melflufen is a next generation form of the more historical drug, melphalan 180 (Figure 3). 5.2.2. Gastrazole (JB95008), 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

• the important anticancer drug suberoylanilide hydroxamic acid (SAHA) from its α,ß-didehydro derivative is described. The didehydro derivative is obtained through a cross metathesis reaction between a suitable terminal alkene and N-benzyloxyacrylamide. Some of the didehydro derivatives of SAHA were

• species (ROS) as some apoptotic features. Keywords: anticancer drug; cross metathesis; HDAC inhibition; hydroxamates; reactive oxygen species; Introduction Suberoylanilide hydroxamic acid (SAHA, 1, Figure 1, vorinostat [1][2], has now emerged as a FDA approved drug for the treatment of relapsed and

• significant changes in biological activity [14]. Three syntheses of this important anticancer drug have been described [15][16][17]. However, need for the development of alternative synthetic routes amenable for SAR studies does exist. Although a number of α,ß-dehydrohydroxamates (e.g., 2 and 3) display an

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

• inexpensive carbon sources. Prominent examples of optimized terpene production pathways in E. coli are taxadiene, a precursor of the anticancer drug taxol [28], amorpha‐4,11‐diene, an antimalarial drug precursor [29], and cyclooctatin [30]. The scope of this review encompasses a detailed consideration of the

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• anticancer drug resistance as they are co-administrated with other chemotherapeutics [29][30]. Nevertheless, there is some controversy about the effects of short-chain fatty acids on the metastatic ability of melanoma cells, since both pro-invasive [31] and anti-invasive [29][32] activities have been

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• published by Cook [76]. The authors also further establish the immediate value of the procedure to LSF by exploring SAR of camptothecin, a molecule identified as an anticancer drug candidate. The authors selectively manipulated the C-7 position, which has been shown to improve efficacy when alkylated

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• , once incorporated into targeted cancer cells thanks to the multivalent platform. Keywords: anticancer drug; calixarene; cell targeting; RGD peptide; ruthenium complex; Introduction Long-living luminescent polyazaaromatic ruthenium(II) complexes are intensively studied in a biological context, in

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• in compounds with increased therapeutic efficacy. The objective of the present study was to examine the cytotoxic effect of anticancer drug–GnRH-conjugates against two essential cardiovascular cell types, such as cardiomyocytes and endothelial cells. Sixteen different previously developed GnRH

• ) – exerted no cytotoxic effect on cardiomyocytes. Mixed conjugates containing methotrexate and daunorubicin – GnRH-III(Mtx-K(Dau=Aoa)) and [4Lys(Mtx)]-GnRH-III(Dau=Aoa) – showed no cytotoxic effect on cardiomyocytes, as well. Conclusion: Based on these results, anticancer drug–GnRH-based conjugates with no

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• [4]. Selective inhibition of the ribosomal machinery has been shown to be an effective anticancer therapeutic strategy [5]. That is why selective drug transport to the nucleoli has emerged a potent new strategy in anticancer drug development [6][7]. Based on these homing domains, a substantial number

• initial study for the delivery of the anticancer drug doxorubicin. Results and Discussion Peptide synthesis and analysis of the secondary structure We chose two different nuclear-targeting sequences, on the one hand the N50 peptide, which was derived from the NF-κB/p50 subunit. N50 binds the adaptor

• uptake was not completely reduced, indicating the involvement of direct entry processes that may play a role during cellular uptake. Use of novel peptides as cargo delivery systems In the last experiment, we investigated if the peptides could be used to enhance the efficacy of an anticancer drug

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• anticancer drug due to its improved cytotoxicity/myelotoxicity ratio [47][48]. Brostacillin acts as an effective DNA alkylator only in presence of high levels of cellular thiols such as glutathione [49]. Moreover, it was thirty-fold more active in comparison to TAM in inducing apoptosis in A2780 human

• , DNA-melting experiments, and circular dichroism (CD) analysis revealed these conjugates are high affinity sequence specific DNA groove binders and could successfully recognize a C·C mismatch in a DNA duplex. Recently, the binding mechanism of the anticancer drug cytarabine with calf thymus DNA (ct-DNA

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• synthesized by SPPS on a Rink-Amide MBHA Resin, using Fmoc/t-Bu strategy. The anticancer drug daunomycin was conjugated to the Aoa-GFLGK spacer via oxime linkage [17]. This spacer is degraded by lysosomal enzymes ensuring the release of the Dau=Aoa-Gly-OH as the smallest bioactive metabolite in lysosomes [19

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• guaranteed. By the application of various cyclic imines and subsequently extended by the use of nonracemic derivatives, a wide range of enantiomeric polyheterocyclic compounds could be isolated and might be tested as potential anticancer drug candidates. Formation of amidoalkylnaphthols 4 via o-QM

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• promising candidate to biomedical applications [8]. Indeed, ZIF-8 has been largely used to encapsulate APIs such as doxorubicin, an anticancer drug [96][142] or even as an efficient pH-sensitive drug-delivery system [92][95][143][144]. Usually, the encapsulation of small molecules into MOFs involves two

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• and ring enlargement, with structural similarity to the simple product from the Ti(IV) reaction with 4a. The reducing agent is Pt(II), which is oxidised to Pt(III) during the reaction (Scheme 3d) [34]. Scheme 3 also depicts paclitaxel (taxol, 11), an important anticancer drug, as there are some

• analogous to the one observed previously with the bis-phenylalkynyl compound [27] as a starting material. Cyclisation of the alkynes and a three-carbon ring enlargement lead in a single step to a rare bicyclic carbon framework that bears some similarity to that of the anticancer drug paclitaxel. Remarkably

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• , hosting methotrexate (MTX), an anticancer drug. The anticancer therapy based on platinum compounds, such as cisplatin, carboplatin and oxaliplatin, has many positive effects on the regression of cancer cell proliferation. Unfortunately these compounds are low tolerated by the organisms, therefore new

• glucose and galactose moieties multi-displayed on gold surface acted as target for asialoglycoprotein receptors, over-expressed on liver cancer cells, delivering selectively the anticancer drug Au(I). In search of novel antimicrobial antigens, chitosan-streptomycin GAuNPs (CA NPs), i.e., carbohydrate

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• Isoprenoid natural products are one of the most structurally diverse groups of primary and secondary metabolites in all kinds of organisms. Moreover, they represent an invaluable source of bioactive natural products. Prominent representatives of these compounds are taxol [1] (paclitaxel, anticancer drug

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• promising as an anticancer drug [1][2][3]. The antiviral activity of ribavirin is ascribed to a combination of different mechanisms [4]. Although RBV causes some side effects [5][6][7] essentially due to its accumulation in red blood cells, it is indispensable in the treatment against hepatitis C virus (HCV

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• carboxylic acids that could be functionalised. Surface conjugation with PEG-diamine afforded a steric blocking, enhanced permeation and retention (EPR) shell, whilst providing an amine functionality for further surface conjugation. The anticancer drug methotrexate (MTX), which is a well-studied drug used to

Chromium(II)-catalyzed enantioselective arylation of ketones

• Gang Wang,
• Shutao Sun,
• Ying Mao,
• Zhiyu Xie and
• Lei Liu

Beilstein J. Org. Chem. 2016, 12, 2771–2775, doi:10.3762/bjoc.12.275

• pharmaceutical study, finally leading to the discovery of the anticancer drug Eribulin [31][32][33][34][35]. However, to our knowledge, the Cr-catalyzed enantioselective arylation of carbonyl compounds has rarely been explored. On the other hand, most of the reactions focused on aldehyde components, while

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• -aza-2'-deoxycytidine (14; anticancer drug Decitabine) catalyzed by E. coli PNP is reversible and condensation of 5-azacytosine with 2-deoxy-α-D-ribofuranose-1-phosphate resulted in the formation of nucleoside 14. The C-5 tert-butyl and phenyl derivatives of 6-azapyrimidines 15 and 16 as well as their

• . coli UP, TP and PNP: The aforementioned contradictory data prompted us to test the substrate properties of 2-thiouridine (9), 2-thio-5-methoxyuridine (10), 4-thiothymidine (11a), 2-thiothymidine (11b), 6-methyl-2-thiouridine (12), 5-azacytidine (13; aC) and 5-aza-2′-deoxycytidine (14; aCd; anticancer

• drug Decitabine) (Figure 5) [25][59] for E. coli UP, TP and PNP (for reaction conditions, see Experimental section). We found that compounds 9–11a,b are good substrates for both UP and TP (see also Figures 1, 2 and 4); 6-methyl-2-thiouridine (12) showed no substrate activity for both nucleoside

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• hydroxyepoxide 116 is simultaneously activated by acidic and basic residues [116]. 1.4 Oxetans Oxetans are present in several isoprenoid natural products with important biological activity, like the anticancer drug paclitaxel or merrilactone A [117][118][119][120][121][122]. However, to the best of our knowledge

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• introduction of a sugar moiety to anticancer drug molecules enhanced their activity and selectivity [30][31]. In this paper, we describe process of synthesis, structural characteristics, and mutagenic activity profile of eight new QAS derivatives of 6-aminohexyl D-glucopyranosides. These compounds correspond

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• hydrogel formed through the initial formation of micelles of poly(ethylene glycol)-b-poly(acrylate), PEG-b-PAA, copolymer and the widely used anticancer drug cis-diamminedichloroplatinum(II), cisplatin [91], and subsequent host–guest complexation by α-CD has been developed by Zhu et al. (Figure 12) [92