On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• breast cancer, colon & rectum cancer [1]. Notably, more than 12 million cancer cases and 7 million cancer deaths are estimated to have occurred both in males and females in 2008 worldwide [2]. These numbers have mounted up to 15 million cases and 8.8 million deaths in 2015. These statistics clearly

• most common anticancer agents used against a wide variety of tumors. It is sold under the brand name Taxol by Bristol-Myers Squibb Company and is FDA approved for the treatment of breast cancer, ovarian cancer, non-small cell lung cancer and AIDS-related Kaposi's sarcoma. The main disadvantages in the

• of other types of cancers (breast cancer, bladder cancer, Kaposi's sarcoma) in combination with other anti-cancer agents. Camptothecin (CPT): Camptothecin is a cytotoxic alkaloid collected from extraction of the bark and stem of the Chinese tree ‘Camptotheca acuminata’. It was first isolated and

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• hydrogenation afforded the optically pure carbocyclic tubercidine analogue (−)-53. This compound has shown potent activity against breast cancer cell lines and human foreskin fibroblasts [53]. Conclusion With increasing reports of emerging and reemerging infectious diseases globally, there is a need to develop

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• , 9Pro-EA] and triporelin [6D-Trp], which are used as pharmaceutical peptides to treat inter alia hormone dependent prostate and/or breast cancer [7]. Since the mid-1980s cytotoxic GnRH-I derivatives were developed and investigated to treat tumor cells [4][5][8][9]. Anthracyclines such as doxorubicin

• uptake and the antitumor activity [29]. Moreover, these GnRH-III bioconjugates displayed an enhanced stability in the presence of gastrointestinal enzymes. The most potent and efficient bioconjugate which has been evaluated in in vitro cytostatic effect measurements on human breast cancer cells (MCF7

• ][49]. Due to this, the usage of internal standards during the evaluation of new potential candidates might be necessary to ensure comparability with previous results. The cytostatic effect of the novel GnRH-III bioconjugates was determined on HT-29 human colon cancer and MCF-7 human breast cancer cell

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• a slight enhancement in toxicity over α-amanitin was observed. The transmembrane receptor αVβ3 integrin is widely expressed on the blood vessels of several human cancers (for example, breast cancer, glioblastoma, pancreatic tumor, prostate carcinoma) but not on the vasculature of healthy tissues [9

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• it through the reactor for a better performance. Case study 2: Multistep flow synthesis for tamoxifen (telescope synthesis) Steven Ley and co-workers have reported a continuous multistep synthesis protocol for tamoxifen, a drug used for treating breast cancer [11]. The synthesis protocol is shown in

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• different cancer cell lines viz., MDA-MB-231, breast cancer (ATCC® HTB-26™); SKOV3, ovarian cancer (ATCC® HTB-77™); MCF7, breast cancer (ATCC® HTB-22™); DU 145, prostate cancer (ATCC® HTB-81™); HepG2, liver hepatocellular carcinoma (ATCC® HB-8065™) were obtained from the ATCC (Bethesda, MD, USA) and

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• estrogen receptors (ER) has been discovered, thereby suggesting it as a promising drug lead for the treatment of breast cancer [18]. Our continuing interest in this area led us to design an alternative approach to oligostilbenoids. As shown in Scheme 1, our idea stemmed from recognition of the symmetry

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• metastatic breast cancer treatment, demonstrating the therapeutic potential of myxobacterial secondary metabolites [29][30][31]. This drug has also been assessed as chemotherapeutic agent in pancreatic lymphoma showing promising results and tolerable toxicity [32]. Over time, different strategies have been

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• triarylmethane intermediate towards an anti-breast-cancer drug candidate. Keywords: copper; modular synthesis; triarylmethanes; Introduction The triarylmethanes form an exclusive group of organic molecules wherein three aryl groups are attached to the central sp3-hybridized carbon atom bearing a hydrogen atom

• turbomycin (3) is an antibacterial medicinal drug (Figure 1). Genuine triarylmethane 4, having three different aryl groups on the central CH, is a proven anti-breast-cancer agent [20]. In addition to 4, several other triarylmethanes exhibit interesting biological activity, including oestrogen receptor

• designed a synthesis of the precursor 22 (Scheme 5) for the anti-breast-cancer agent 4 (Figure 1). Any method for the synthesis of 4 needs to take into account that it has two phenyl rings with different alkoxy groups at the respective C(4) position. We reasoned that one of the aryl groups could be a part

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• in the diagnosis of breast cancer with this imaging technique [33][34]. Considering the synthetic and biological importance of inositol analogues, the design of new inositol derivatives to study their biological properties and to understand their binding mechanisms with molecular targets, for

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• , inhibition of chronic venous insufficiency and hemorrhoids, and prevention of post-operative thromboembolism [17]. Hesperetin can inhibit chemically induced mammary [18], urinary bladder [19], colon carcinogenesis in laboratory animals [20][21][22], and proliferation of breast cancer cells (MCF-7) [23][24

• ]. Naringenin has the ability to hinder a tumor growth on various human cancer cell lines [25], and acts as an inhibitor that blocks basal and insulin-stimulated glucose uptake in breast cancer cells [26]. Additionally, naringenin reduces the incidence of hormone-responsive cancer [27]. In spite of having

• cancer cell lines (CaCo-2, HeLa and MCF-7) has been determined by MTT assay which measures the metabolic activity and thus viability of cells based on their ability to reduce the tetrazolium substrate to formazan. For the breast cancer cell line (MCF-7), naringenin and their complexes exhibited cytotoxic

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• showed mild toxicity against the breast cancer cell line MCF-7 and to FS4-LTM conditional immortalization human fibroblasts (IC50 = 78 and 32 µM, respectively). The cytotoxicities of the known compounds (4–17) are also listed in Table 5. None of the isolated compounds showed any antimicrobial activity

• proliferation assays. Targeting cell lines are L929 mouse fibroblasts, KB-31 epidermoid carcinoma, and MCF-7 breast cancer cell lines which were incubated for 5 days with the test substances. The acute toxicity was determined using the FS4-LTM conditional immortalization human fibroblasts cell line which was

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• their developmental therapeutics program. Interestingly, at the tested concentration of 10 μM, panicein A2 (5) showed very little activity against most cell lines. The best performance of panicein A2 (5) was against T-47D, a breast cancer cell line, in which it showed a 43% reduction of growth when

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• cells, causing an extensive reduction of the MCF-7 breast cancer cells in the G2/M phase [85]. Two skeletons, including 9H-pyrido[4,3,2-mn]thiazolo[4,5-b]acridin-9-one and 8H-pyrido[4,3,2-mn]thiazolo[4,5-b]acridine (Figure 15), are found in kuanoniamine structures (60, 86–88). The first one associated

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• , selected compounds were assessed for in vitro antiplasmodial (Plasmodium falciparum; drug resistant K1 strain) activity [15], cell-based anticancer activity (cell lines: NCI-H187 small cell lung cancer, KB oral cavity cancer, and MCF-7 breast cancer) [16], and in vitro antitubercular activity

• , respectively), but not against the more refractory MCF-7 breast cancer cell line [16]. Additionally, 17 exhibited some antitubercular activity (MIC 12.5 µg/mL, 38.6 µM), providing a basis for further structurally novel lead development of anti-TB compounds. The need for such compounds is a pressing one with

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• capable of binding to the native MUC1 antigen structures present on MCF-7 human breast cancer cells. Moreover, selective deoxyfluorination at the antigenic carbohydrate determinant might be used to improve the metabolic stability of the saccharide epitope, as was showcased by the enhanced resistance of

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• –18; LC–MS trace of crude 18. Supporting Information File 8: CIF file of 8, CCDC 1018518. Acknowledgements We thank the National Breast Cancer Foundation for a Novel Concept Grant (NC-10-69) and the Australian Research Council for funding (DP120104035). M. Yu was supported by a University of Sydney

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• )diphenol. The in vitro cytotoxic activities of compounds 1–4 against HL-60 (human leukemia), HeLa (human cervical carcinoma), and MCF-7 (human breast cancer) cells were evaluated using an MTT assay. As shown in Table 4, compounds 1–3 exerted moderate cytotoxic effects against HL-60 cells with IC50 values

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• myeloid leukemia, SH-SY5Y neuroblastoma, SGC-7901 gastric adenocarcinoma, HepG2, SMMC-7721 hepatocellular carcinoma, A549 lung cancer, MCF-7, MDA-MB-231 breast cancer, HCT116, SW480 colon cancer, HT29 colorectal cancer. However, no significant activity was detected (IC50 > 50 μM). It also displayed no

• desposit@ccdc.cam.ac.uk. Biological assays Cytotoxic activity against 11 human cancer cell lines, K562 myeloid leukemia, SH-SY5Y beuroblastoma, SGC-7901 gastric adenocarcinoma, HepG2, SMMC-7721 hepatocellular carcinoma, A549 lung cancer, MCF-7, MDA-MB-231 breast cancer, HCT116, SW480 colon cancer, HT29

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• such as cancer [133][134] and obesity [99], automated SPPS also offers a versatile repertoire. As an example, a method to produce radiolabeled Y1-receptor preferring agonists of NPY has been described, which could selectively target breast cancer cells and allowed specific tumor diagnosis. Here, the Nα

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• cause problems of the reproductive tract (e.g., impaired fertility) in animals [7]. Physiological studies revealed binding of ZEN to recombinant human estrogen receptors [8] and have furthermore shown a ZEN-induced stimulation of the growth of human breast cancer cells [9]. Additionally, masked

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• (4) exhibited mild antiproliferation activity against L929 mouse fibroblast, KB-31 epidermoid carcinoma, and MCF-7 breast cancer cell lines, while siphondictyal E3 (3) and cyclosiphonodictyol A (5) showed moderate activity against Gram-positive bacteria. Keywords: Aka coralliphagum; bioassay

• ) show cytotoxic activity against the L929 mouse fibroblasts, KB-31 epidermoid carcinoma, and the breast cancer cell line MCF7, although none of them showed activity in the antimicrobial assays against Gram-negative bacteria and the fungus Candida albicans. Many of the isolated compounds from Aka

• , targeting cell lines L929 mouse fibroblasts, KB-31 epidermoid carcinoma, MCF-7 breast cancer, and FS4-LTM conditional immortalization human fibroblasts, respectively. The FS4-LTM cell line was incubated for 24 hours with the tested substances. The other cell lines were incubated for 5 days with the tested

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• than that of paclitaxel. The breast cancer cell lines MAXF-401 (IC70 0.2 nM) and MCF-7 (0.5 nM), the colon cancer cell lines HT-29 (0.3 nM) and RKO (0.5 nM), the lung cancer cell line H460 (0.7 nM), the liver cancer cell line LIXF-575 (0.6 nM), and the renal cancer cell line RXF-393 (0.4 nM) all proved

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265