Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• ][22][23][24][25][26]. Some oxazoles play a significant role in biological properties such as TRPV1 antagonistical activity, antifungal, analgesic, anti-inflammatory, antiproliferative, antileukemia, anticancer [27][28][29][30][31][32] and enzyme inhibitory activities [33][34][35][36][37][38][39][40

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• with their complex structure, a number of total syntheses have been reported. This review will compare the synthetic strategies reported through the end of 2019. Keywords: antiproliferative; polyketide natural products; tetrahydropyrans; total synthesis; Introduction The spliceostatins/thailanstatins

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

• fully reduced form of BER, namely tetrahydroberberine (THBER), and its derivatives have proven to present different biological activities. Therefore, the obtained arylhydrazono-functionalized DHBERs were reduced to the corresponding arylhydrazono-THBERs. The antiproliferative activity of both

• arylhydrazono-DHBERs and -THBERs has been evaluated on NCI-H1975 lung cancer cells. Keywords: antiproliferative agent; dihydroberberine; hydrazones; reduction; tetrahydroberberine; Introduction The rhizome of Coptis chinensis Franch. is a common remedy in traditional oriental medicine for the treatment of

• ; in particular, we focused our attention on their antiproliferative capacity, due to our previous research experiences on the anticancer properties of both natural and synthetic molecules [39][40][41][42]. A common strategy to increase the biological activity of a class of products can be the

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

• potential antioxidants and showed antiproliferative activity [27][28]. Consequently, they have attracted much attention, and methods for their syntheses have been actively pursued. A powerful method for the synthesis of 3-selanylimidazo[1,2-a]pyridines involves the C–H selenation using imidazopyridine and a

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• modifications at the C3-OH group of 18β-glycyrrhetinic acid are identified to be relatively common and effective. The modification of the C3-OH group, altering the molecular polarity of 18β-glycyrrhetinic acid, may be an advantage in achieving better cytotoxicity or antiproliferative activity [8][9][10]. For

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

• for antimitotic potency in cellulo, since the degree of resazurin turnover scales to the number of cells still viable after compound treatment, although the mechanism behind antiproliferative activity must later be determined using more specific assays. We used the HeLa human cervical cancer cell line

• ) delivered results equivalent to dark conditions (exclusively Z-configuration), to which 450 nm (lit conditions, ca. 70% E-configuration) gave the greatest difference in antiproliferative potencies. We began our studies with HITub-1. This is a HTI analogue of indanocine in which the indanocine amino function

• class of photoswitchably antiproliferative agents, with the most potent light-controlled antimitotic bioactivity reported for photoswitches designed for tubulin: 10-fold enhancement compared to the predecessor HTI generation HOTubs [18] and styrylbenzothiazole-based SBTubs [17], and 5-fold superior to

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• applications as antibiotics [1], antiproliferative agents [2], anti-inflammatories [3] and antithrombotics [4]. They are also found in many bioactive natural products [5][6][7][8], some of which display anti-HIV-1 [9] and antimitotic activities [10], among others. Thiazolines also find use in organic synthesis

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• ]. In parallel, bioorganometallic chemistry provides new tools to influence biological interactions [16][17][18][19][20][21][22][23][24]. Cobalt possesses a diverse array of properties that can be manipulated to yield promising drug candidates [25]. The antiproliferative properties [26], as well as

• hexacarbonyls with 2'-deoxyuridines revealed pronounced in vitro activity against MCF-7 and MDA-MB-231 human breast cancer cells [32][33]. A recent investigation of hexacarbonyl dicobalt adducts of nucleosides containing derivatives of propargyl alcohol demonstrated their antiproliferative activities for the

• HeLa and K562 cell lines [31]. The formation of a reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress [31

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

• intracellular space in a high proportion [59]. Besides the copper complexes, the gold complexes of these dendrimers display higher antiproliferative activities, in particular against both KB and HL-60 tumor cell lines (oral epidermoid carcinoma and human leukaemia, respectively), showing IC50s (the quantity of

• high antiproliferative activities against different tumor cell lines. A fluorescent water-soluble dendrimer, applicable for two-photon photodynamic therapy and imaging. Schematization of the different types of TPA fluorescent phosphorus dendrimers and dendritic structures that have been already

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• Withanolides are steroidal lactones widespread in Nightshade plants with often potent antiproliferative activities. Additionally, the structural diversity of this compound class holds much potential for the discovery of novel biological activity. Here, we report two newly characterised withanolides, named

• irinans, from Physalis peruviana with highly unusual truncated backbones that resemble mammalian androstane sex hormones. Based on biomimetic chemical reactions, we propose a model that links these compounds to withanolide biosynthesis. Irinans have potent antiproliferative activities, that are however

• effects [1][2]. A large range of pharmacological properties has been assigned to withanolides, with antiproliferative activities being the most potent ones [1]. Withanolides have been also discovered in numerous genera other than Withania, for example Datura, Dunalis, Iochroma, Jaborosa, Lycium and

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

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• biological actions: antiproliferative [6][7][8][9], antimicrobial [10][11], anxiolytic [12], analgesic [13], hypnotic [13], antiviral [13], anti-HIV [13] activities, etc. Soural et al. [14] explored different data and showed the relevance of compounds composed of two or more heterocyclic rings for drug

• Plasmodium falciparum 3D7 strain [17]; antagonists of p53-Mdm2 interaction [18]; antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr(colon) [19]; cyclophilin A inhibitory activity for the treatment of hepatitis C

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

• components, keeping formaldehyde as oxo component to obtain a single stereoisomer. The library was also integrated by the Ugi-4CR products derived from the 6β-ecdystereoidal amine (also used as precursor of isocyanide 28), while all compounds were evaluated as antiproliferative agents against T-leukemia cell

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• derivatives show a large variety of biological activities [21][22][23], such as COX-2 inhibition [24], glucokinase activation [25], sodium channel blocking [26], antimycobacterial [27], antiproliferative [28] or carbonic anhydrase inhibition [29], as well as antifungal and antibacterial properties [30

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• , the dihydro-1H-furo[2,3-c]pyrazole system, consisting of an aromatic pyrazole ring fused with a five-membered 2,3-dihydrofuran ring, was formed [8]. Derivatives of the latter system are known for their antimicrobial [9] and antiproliferative activities [10]. Nevertheless, methods to access 2H-furo[2,3

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• shown in Table 1. Furthermore, the PC-3 cells were indeed detected to be the most sensitive cell line compared to HT-29 and Colo320, since PC-3 probably expresses a higher NPY Y1 receptor level and internalizes, consequently, more peptide–toxin conjugate. The antiproliferative activities of the

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• liberation of the arylhydrazines from their hydrochloride salts in EtOH in the presence of NaOAc. The reaction rates were found to depend on the electronic character of the substituent present in the phenylhydrazine applied. The antiproliferative activities of the structurally related steroidal pyrazol-5

• the reference compound, cisplatin. Keywords: antiproliferative activity; Knorr reaction; microwave; pyrazol-5-ones; steroids; Introduction 17-exo-Heterocyclic androstanes with five or six-membered heterocyclic rings connected directly to C-17 of the sterane core represent a remarkable subclass of

• core, using both conventional heating and MW irradiation. The reaction conditions were optimized in order to improve the yields of the desired products and the influences of substituents of the hydrazine reagents investigated. The in vitro antiproliferative activities of the synthesized compounds were

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

• synthetic derivatives have been reported to exert an antiproliferative effect in different types of tumors related (e.g., breast, endometrial cancer [5]) and unrelated (e.g., melanoma, colon carcinoma [6][7]) to reproductive organs. Considering these aspects, the GnRH could serve as a targeting unit with

• of GnRH, could display strong antiproliferative effects in the breast, prostate, colon carcinoma cell lines, whereas induce 500–1000 times less LH-release than GnRH-I derivatives [14]. In our previous studies, the side chain of Lys8 was used for attachment of daunorubicin (Dau) via a more stable

• antiproliferative/cytotoxic activities, the cell adhesion and migration modulator effects of conjugates and their ability to induce apoptosis or cell cycle arrest in A2058 melanoma cell line. Results and Discussion Synthesis of Dau–GnRH-III conjugates The modified GnRH-III derivatives were prepared by solid phase

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• green alga Caulerpa taxifolia, exhibits antiproliferative activities as well as wound healing abilities with the latter resulting from rapid transformation to the highly reactive 1,4-dialdehyde, oxytoxin 2 (4) [4][5][6]. Oxytoxin 2 (4) is itself a natural product, produced by the mollusc Oxynoe olivacea

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

• . Small peptides that recognize target receptors on tumor cells might be suitable targeting moieties for this purpose. Hormone peptides, in particular, GnRH and somatostatin derivatives that possess antiproliferative effect on their own, are among the best candidates as homing peptides [10]. A.V. Schally

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

• the past few years. Keywords: alkylators; antibiotic; anticancer; antineoplastic; antiproliferative; DNA recognition; groove binders; hairpin polyamides; Hoechst 33258; intercalators; Review 1. Introduction DNA is one of the central components of cellular machinery and storage unit of genetic

• . Szerszenowicz et al. developed a new set of potential minor groove binders derived from netropsin and bis-netropsin analogs by replacing N-methylpyrrole rings with other heterocyclic rings and their antiproliferative activity was tested on MCF-7 breast cancer cells [60]. Suckling et al. recently designed and

• evaluated their antiproliferative activity as well as their DNA binding affinity [98]. It has been confirmed that the most active conjugates are unsymmetrical triaryl benzamides 35 and 36 comprising of a bulky and alkylating chlorobenzylic substituent, respectively, and a polar amino side chain. Conjugate

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• estrogen receptors (ERα and ERβ) [28]. Certain derivatives of 2- or 4-aminoestrone or their 3-methyl ether possess diverse biological activities, including enzyme inhibitory or antiproliferative properties [1][2][3][29][30]. The 17β-HSD1 enzyme is responsible for the reduction of estrone into 17β-estradiol

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

• . Another natural isoform of GnRH is GnRH-III (pGlu-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2), which has been isolated from sea lamprey. GnRH-III binds to GnRH-R overexpressed on the cancer cell surface, resulting in an antiproliferative effect but seems to be less potent than the rest GnRH analogs regarding

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

• antiproliferative activity. Furthermore, the absence of the free ε-amino group additionally reduced the endocrine effect [23][24]. Thus, the 8Lys can be utilized as conjugation site for cytotoxic agents like anthracyclines. In the past decade, a variety of different linkage systems has been carried out including

• receptor binding affinity and an enhanced antiproliferative activity without substantial effect on the endocrine activity [31][32][33], we developed six novel GnRH-III–Dau conjugates in which the 6Asp was replaced by D-Aaa. Here we report on the synthesis of GnRH-III bioconjugates containing D-Asp, D-Glu

• of the antiproliferative activity between the 4Ser and the corresponding 4Lys(Bu) derivatives could be observed which is not in line with our previous data [29]. This might be a result of the prolonged incubation time which was modified from 6 hours up to 24 hours because of the decreased antitumor

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

• antiproliferative activity of the conjugates was evaluated in three cell lines possessing different levels of αVβ3 integrin expression: human glioblastoma U87 (αVβ3+), human lung carcinoma A549 (αVβ3−) and breast adenocarcinoma MDA-MB-468 (αVβ3−). In the U87, in the MDA-MB-468, and partly in the A549 cancer cell

• , cyclo[DKP-RGD]-Val-Ala-PTX 5 and cyclo[DKP-isoDGR]-Val-Ala-PTX 6). Their tumor targeting ability was assessed in vitro in antiproliferative assays comparing an αVβ3 positive with an αVβ3 negative cell line [29][30]. The cyclo[DKP-isoDGR]-Val-Ala-PTX conjugate 6 displayed a remarkable targeting index (TI

• αVβ3 expressing tumor cells. Cell viability assays The antiproliferative activity of the conjugates was evaluated in three cell lines expressing different levels of αVβ3 integrin. U87 cells (human glioblastoma) were selected as αVβ3 positive, while A549 cells (human lung carcinoma) and MDA-MB-468