Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• work we described the synthesis and antiviral activity of some 4-oxoquinoline acyclonucleosides 3a and 3b [15] and studies on their anticancer activity are also underway. It is also worth mentioning that derivative 4 presented an excellent inhibitory profile for the enzyme hystone deacetylase (HDAC

• ), and anticancer activity for three cancer cell lines (Figure 1) [16]. Although it is not a general rule for achieving a bioactive profile, any groups attached to C-3 of the 4-oxoquinoline moiety, especially those containing a hydrogen bond donor group, such as a carboxyl, an acyl hydrazide or a

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• promising anticancer activity [34], thereby showing the importance of this merged heterocyclic skeleton (Figure 1). The formation of the chromene and imidazole rings in a single-step procedure was independently discovered by us [35][36] and Proença et al. [37][38], who identified 2-iminochromene 3 to be the

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• ] and the didehydrohydroxamate TSA (2) [24], display useful anticancer properties through inhibition of histone deacetylase enzymes (HDAc) and are used as FDA-approved drugs. Similarly, the cyclic peptide Chap-31 (3) [25] with a terminal hydroxamic acid residue has shown promising anticancer activity

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• vinyl ethers as key step of reaction sequences developed. Keywords: 3-amino glycals; diastereoselective additions to aldehydes; pluramycins; ring-closing metathesis; vinyl ethers; Introduction Several classes of medicinally useful molecules with antibiotic and anticancer activity contain in their

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• the blood stream, but also be effectively dis-assembled in the acidic tumor environment, and thus improve the anticancer activity of oxaliplatin in vivo. In 2015, we introduced a new class of macrocyclic arenes, 4,4’-biphen[n]arenes (n = 3,4) with 4,4’-biphenol or 4,4’-biphenol ether monomers linked

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• show that both a natural antimicrobial peptide (AMP) derived from wasp venom (decoralin, Dec-NH2), and its synthetic variants generated via peptide design, display potent activity against cancer cells. We tested the derivatives at increasing doses and observed anticancer activity at concentrations as

• membranes increased significantly when treated with lead peptides compared to controls. Biophysical features such as helicity, hydrophobicity, and net positive charge were identified to play an important role in the anticancer activity of the peptides. Indeed, abrupt changes in peptide hydrophobicity and

• ][7][8], and fungi [1][9][10], they can kill cancer cells [11]. So far, >2,500 AMPs have been described in the literature and only ≈10% of those are known to exhibit anticancer activity, according to the Antimicrobial Peptide Database (http://aps.unmc.edu/AP/main.php). In total, there are around 600

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• ]. In spite of the fact that parent indole is too weak an acid to undergo Mitsunobu conversions, a model maleimide–indole hybrid was investigated by Ohkubo and colleagues to pave the way for the synthesis of indolo[2,3-a]pyrrolo[3,4-c]carbazole compounds with anticancer activity [90][91]. N-Glycosides

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• oxidation of black tea and have been found to have numerous biological activities such as antipathogenic and anticancer activity, and they prevent heart disease, hypertension, and diabetes (Figure 1) [39][43]. Because of the pharmacological relevance of benzotropone analogues, the development of new and

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• –hydroxybenzotriazole (Scheme 38). The compounds were found to possess good anticancer activity against human colon, leukemia, melanoma cancer cell lines. In another report, Kamal et al. [95] synthesized similar pyrazolo[1,5-a]pyrimidinyl amide derivatives (piperazinyl derivatives, 136) by condensing piperazin-1-yl

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• the synthesis of kinamycin 9 derivatives, which exhibited a strong cytotoxic and anticancer activity (Scheme 4) [15]. Propionic acid derivatives are also useful substrates in syntheses of 1-indanones and isocoumarins [16]. These latter are essential reagents for the synthesis of bioactive compounds

• -aryl-2-phosphoryl-1-indanones 147 which exhibited anticancer activity against HeLa and K562 cell lines at the µM level [73]. Both groups of products have been obtained from the corresponding phosphorylated chalcones (Z)-145 or nonphosphorylated chalcones (E)-146, in selective Horner–Wittig or

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

• compounds for their anticancer activity [18]. The anticancer activity of compounds 3a–e was tested against five cell lines along with doxorubicin as positive control and all of them showed moderate to good anticancer effects. The results are collected in Table 3. The compounds whose IC50 values are observed

• to be lower and closer to the reference drug are considered as having good anticancer potential. Specifically compounds 3c, 3b and 3e were found to show promising anticancer activity according to their IC50 values, whereas 3d and 3a exhibited only moderate activity. Among all tested derivatives

• , compound 3c was found to exhibit best anticancer activity against MCF7, DU145 and MDA-MB-231 cell lines with IC50 values of 10.55, 13.0 and 12.0 µM, respectively. It was found that the anticancer activity against some cell lines was much better compared to our previous reports on phenolic lipids [19

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• greater anticancer activity than free gemcitabine against different experimental tumor models [7][8][9][10][11] overcoming the main drawbacks of the parent drug such as its short biological half-life and its low intracellular diffusion [12][13]. Following these initial results, the squalenoylation method

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• macrocyclic 26-membered lactam precursor. Although compound 24 lacks any significant antimicrobial and anticancer activity, it was shown to act as a Na+/K+ ATPase inhibitor. Subsequent studies by the same group lead to the isolation of phenylpyridines (e.g., coprismycin A (25)), dipyridines (e.g., collismycin

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• 16–20 and 2-amino-6-substituted purine 3’-deoxy-3’-fluororiboses 21–23 (Figure 2). In addition, their anticancer activity was evaluated. Results and Discussion Current strategies to the synthesis of 3’-fluorine and 6-substituted purine require harsh conditions and laborious protecting group

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• product 330 (79%). Further, the building block 330 was used in the stereoselective total synthesis of lepadin B (Scheme 72). Bicyco[3.2.1]octene derivatives Norhalichondrin B is a marine polyether belonging to the halichondrin family and its macrolactone analog has displayed anticancer activity. Phillips

Pd(OAc)₂-catalyzed dehydrogenative C–H activation: An expedient synthesis of uracil-annulated β-carbolinones

• Biplab Mondal,
• Somjit Hazra,
• Tarun K. Panda and
• Brindaban Roy

Beilstein J. Org. Chem. 2015, 11, 1360–1366, doi:10.3762/bjoc.11.146

• Alstonia venenata, and substituted 1-oxo-13-carbolines were also shown to have serotonin-receptor-binding activity (5-HT receptor) [14]. Moreover the natural and synthetic β-carbolines are also known to show anticancer activity against colon and lung cancers, and some β-carbolinones act as biological

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

• and benzo[b]indolo[1,2-h]naphthyridine heterocycles in one-pot, multi-step cascade sequences [3]. These ring systems are not only of chemical interest but biological testing revealed promising in vitro antiplasmodial activity and anticancer activity in certain cases [3]. While the analogous base

• , 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

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• ]: Some of these compounds show a good anticancer activity against the anaplastic (8305C) and the follicular (FTC-133) human thyroid cancer cell lines, and especially on the U87MG human primary glioblastoma cell line (Figure 2). Accordingly, considering that the incorporation of the triazole moiety can

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• -glucuronidase activity is possible [86]. Fisetin can be found in many fruits such as strawberries and apples (Malus spec. MILL., Rosaceae) as well as in vegetables such as onions (Allium cepa L., Amaryllidaceae, subfamily Allioideae former family Alliaceae). It shows anticancer activity in various cancer models

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• potent anticancer activity by inhibition of topoisomerase II. Its major drawback is its extremely low aqueous solubility of 2.5 µg/mL leading to a low bioavailability and it is thus a considerable formulation challenge [4]. Furthermore, at physiological conditions its active lactone form is hydrolysed to

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• benefits exhibited by RSV (including, e.g., anti-inflammatory effects, cardiovascular protection, and anticancer activity [3]) has increased considerably. Its low aqueous solubility, however, is one of the factors that limits its utility [4] and various methods have been employed to address this

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• -inhibiting and antialgal properties [49], show anticancer activity [50][51], and are inhibitors of bacterial enzyme synthetase MurD with E. coli [52]. Additional treatment of thiazolidin-4-one 8 with a fivefold excess of hydrazine hydrate resulted in the formation of a 1H-pyrazole: A total of two hydrazine

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• interest from research groups in biology, chemistry and medicine [1][2][3][4]. As the first identified hedgehog signaling inhibitor, cyclopamine exerts its anticancer activity through a novel mechanism of action, which manifests itself in its remarkable activity against several types of human cancer

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• vincristine-resistant KB cancer cells [23][24]. Minfiensine alkaloid [25][26][27][28][29][30][31] containing a novel 1,2,3,4-tetrahydrocarbazole ring skeleton shows anticancer activity [32]. König and co-workers identified some propellane derivatives as cannabinoid CB1 receptor antagonists [33], which are

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• with aldehydes furnished tetrahydro-β-carboline 3 and indolo[1,2-a]quinoxaline 8, respectively. The β-carboline skeleton is widely distributed in marine organisms [54][55][56]. Eudistomine and manzamine isolated from marine invertebrates exhibited promising anticancer activity [57][58]. Tedalafil, a