Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• experimentally observed. The base-catalyzed cycloaddition of 3,3-diaminoacrylonitriles 1 to azides 2, thus proceeds in a Cornforth-type fashion, which involves a triazole–triazole isomerization through ring opening, rotation of the amidine substituent around the single bond, and cyclization. Cytotoxic activity

• The cytotoxic activity of seven synthesized compounds 3b,d,e,g,h,l,m was studied. According to the results of the MTT test, IC50 values were calculated for these compounds (Table 2). The results obtained indicated that compounds 3b,e,g,h did not have a pronounced effect on the viability of cultured

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• inducing cytotoxicity. In addition, another study demonstrated that a lanostanoid glycoside derivative with a glucosyl ester at the C-21 carboxylic acid group was active in a cytotoxic activity assay, whereas the galactosyl ester counterpart was inactive [36]. Similarly, the carboxylic acid group at C-21

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• , fragmentation of the mitochondrial tubular network, chromosome misalignment, and cell cycle arrest in mitosis in LNCaP prostate cancer cells [38]. The bastadin structure class is well-documented within the literature for their cytotoxic activity [37][39][40][41], with both bastadins 4 and 8 exhibiting in vitro

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• drug for its treatment, however, its clinical use has been limited due to its side effects. Here, we designed two new nitroaryl-1,2,3-triazole triterpene derivatives as novel anti-RSV drugs. Their anti-RSV and cytotoxic activity were evaluated in vitro, RSV protein F gene effects by RT-PCR and

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• previous report demonstrated the cytotoxic activity of azodyrecins [21]; however, the relationships between the structure and cytotoxicity were not determined. With new azodyrecin analogs with saturated alkyl chains in hand, we attempted to gain insights into the effects of the double bond on cytotoxicity

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• , respectively. Compound 5 also exhibited a significant stimulating effect on NGF secretion (122.77 ± 8.10%). Compound 9 showed potent cytotoxic activity against SK-OV-3 (IC50 = 3.76 μM) and SK-MEL-2 (IC50 = 1.48 μM) cell lines, while 7 displayed a strong cytotoxic activity against the SK-MEL-2 (IC50 = 9.81 μM

• ), and colon adenocarcinoma (HCT15)] were also investigated using a sulforhodamine B (SRB) bioassay (Table 6). Compound 9 showed selective cytotoxic activities against SK-OV-3 and SK-MEL-2 cell lines, with IC50 values of 3.76 and 1.48 μM, respectively. Compound 7 also displayed a cytotoxic activity

• ) as ᴅ-glucopyranoside. GC–MS analysis was perfomed under the following conditions: capillary column, HP-5MS UI (30 m × 0.25 mm × 0.25 μm, Agilent); column temperature, 230 °C; injection temperature, 250 °C; flow rate, 1.0 mL/min; carrier gas, N2 [22]. Cytotoxic activity, NO production, NGF secretion

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• ± 0.04 µM (100 ng/mL, 200 nM), respectively. Two compounds (3b and 10d) have also been tested for anti-SARS-CoV-2, antibacterial, and cytotoxic activity. Keywords: antimalarial activity; anti-SARS-CoV-2 activity; chloroquine; 2-nitroperchlorobutadiene; nucleophilic vinylic substitution; 1H-pyrazoles

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• . Compound 2 possesses a rare bicyclic sesquiterpene skeleton. The antimicrobial and cytotoxic activities of the isolated compounds were evaluated. Keywords: antimicrobial activity; cytotoxic activity; γ-lactone; soil-derived fungus; sesquiterpene; Trichoderma citrinoviride; Introduction The fungus

• amount were evaluated for their antibacterial activity against S. aureus ATCC25923 and methicillin-resistant S. aureus SK1, antifungal activity against C. neoformans ATCC90113 as well as cytotoxic activity against KB, MCF-7, and noncancerous Vero (African green monkey kidney fibroblast) cells. None of

• support. Finally, National Center for Genetic Engineering and Biotechnology (BIOTEC) is acknowledged for evaluation of cytotoxic activity. Funding This work was supported by the NSTDA Chair Professor grant (the Fourth Grant) of the Crown Property Bureau.

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• , demethylgorgosterol [9][10]. Thus, the structure of compound 4 was assigned as shown in Figure 1. Biological activity The cytotoxic activities of compounds 1–7 were evaluated against three cancer cell lines (HL-60, K562, and Hela), but only compound 1 exhibited weak cytotoxic activity against K562 cells with an IC50

• methyl group at C-4. The absolute configuration of 1–3 was determined by X-ray diffraction analyses. Compounds 1–7 were subjected to a cytotoxic activity evaluation against HL-60, K562, and Hela cells, only compound 1 exhibited weak cytotoxic activity against K562 cells with an IC50 value of 19.03 μM. In

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

• ). The EGFR inhibitor drugs bearing the 4-anilinoquinazoline moiety did not show potent cytotoxic activity against T98G cells (21.3 µM for erlotinib, and 37.8 µM for gefitinib). However, the tubulin polymerization inhibitor (verubulin), which contains 4-anilinoquinazoline in its chemical structure, 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

• [4]. These compounds demonstrated cytotoxicity against various human cancer cells. Additionally, the research group led by Pereda-Miranda later isolated more members of brevipolide (1–15) from the same plant during 2013–2017 and further confirmed the cytotoxic activity of these natural products [1

(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

• , 2c, 2d, and 2g with the BCR-Abl-1 structure (PDB code: 3PYY), showing steric interactions (red dotted lines) and hydrogen bonds (blue dotted lines). Synthetic route of the triazole derivatives 1a,b, and 2a–j. Cytotoxic activity, confidence interval, and selectivity index of imatinib and derivatives

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• cytotoxic activity of amino- and polyaminophthalazinone derivatives. Results and Discussion Chemistry Synthesis of aminophthalazinones The synthetic route toward the aminophthalazinones 5 and 6 is shown in Scheme 1 (route B). A current literature review [19][34] and our experience [35] proved, that the

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• ) exhibited mild growth inhibitory effects against A549 and BT549 cell lines with IC50 values of 27.1 and 22.7 μM, respectively (Table 2). Betulinic acid (10) is a well-known anticancer agent inhibiting eukaryotic topoisomerase I [36] and its derivatives have been reported to display cytotoxic activity [13

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• -lactone derivatives spiro-fused to an oxindole (A), one of which exhibited a potent cytotoxic activity [9]. Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a

• results suggest that cytotoxic activity of this type of spirolactams against P388 cells is simply related to the methylene lactone structure [28]. Conclusion In conclusion, we have achieved a new bifurcated syntheses of N-alkyl and N-phenyl-substituted spirolactams bearing a methylene-lactone or methylene

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• , thereby affording the triene intermediate in a substantial yield. Additional transformations using conventional methods efficiently provided (−)-amphidinolide E (3). Amphidinolide K, another important bioactive macrolide endowed with specific cytotoxic activity against L1210 and KB cancer cells, was also

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• myxobacterium Archangium gephyra (Figure 1) [5][6]. These cyclic peptides have interesting biological activities such as cytotoxic activity presumably via proteasome inhibition and immunomodulatory effects, and they also show good antibiotic effects against P. aeruginosa [7][8][9]. The structure–activity

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

• of thiazolidinedione were used to study the cytotoxic activity in comparison with camptothecin and etoposide on Jurkat, K562, HEK293, HELA, A549 and U937 cell lines. Compounds 20 and 17 showed the highest activity (IC50 = 0.29 and 0.36 nM, respectively) for leukemic monocytic lymphoma cells (U937

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• successfully used in the synthesis of tubulysin analogues called tubugis (53–55) [27]. These molecules are N-substituted peptides, which possess a very high cytotoxic activity (on the picomolar range). They were prepared using three different IMCRs (Scheme 11): the Mep-Ileu-OH dipeptide fragment 47 was

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• -mercaptobenzoxazoles are not only fundamental building blocks in organic synthesis, but also possess various biological activities (Figure 1) [1][2]. A complex of a transition metal (such as Ru, Pt, Bi, etc.) with either a 2-mercaptobenzoxazole or a 2-mercaptobenzothiazole often provides cytotoxic activity against

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

• strongly hampered in its cytotoxic activity, and the peptide moiety ensures the target-specific toxin delivery toward the diseased cells, while omitting (most) healthy cells. To assess the impact of the chemical modifications due to the linker-assisted peptide–toxin conjugation and toxin liberation on the

• -SH was – in case of HT-29 and PC-3 – by factors ≈5 to 8 higher compared to the entire peptide–toxin conjugate 8. The only slight increase of cytotoxic activity of compound 9 compared to the complete conjugate 8 in Colo320 cells is most likely caused by a generally weak responsiveness of Colo320 cells

• -qPCR (Figure 2C). Both the cytotoxic activity and the hY1R expression level rank in the order SK-N-MC > MDA-MB-468 > MDA-MB-231 > 184B5, what proofs the hY1R-specific and -selective nature of the mode of antitumor action of the designed PDC 8. Importantly, the activity of 8 against the selected normal

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• on the LuxR type receptors for AHLs in bacteria [23][24]. Other potential functions are antimicrobial or cytotoxic activity of the tested derivatives. Roseovarius sp. D12_1.68 showed antimicrobial activity against a Rhodobacteraceae sp. TL and antialgal activity against Skeletonema costatum while

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

• seen that the presence of acylated Lys could increase almost 10-fold the antitumor activity (p < 0.001) of parent conjugate (GnRH-III(Dau=Aoa)). In case of the acylated 4Lys-containing conjugates, [4Lys(Bu)]-GnRH-III(Dau=Aoa) had a slightly but not significantly higher cytotoxic activity than that of

• native GnRH-III sequence. Despite the increased activity of conjugates substituted with acylated 4Lys, they displayed their dose-dependent cytotoxic activity at higher concentrations comparing to the free Dau. This difference could be explained by the internalization ability of the compounds. The action

• (H-Lys(Dau=)-OH)) formed via lysosomal degradation of this type of conjugates had a lower binding affinity to DNA, than the free drug [35]. The two-fold higher intracellular fluorescence intensity of Dau was accompanied by almost two-fold higher cytotoxic activity compared to the conjugates. By

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• [121] reported the synthesis of various oxygen analogues of naturally occurring compound discorhabdin A starting from substrate 110 in few chemical steps. Discorhabdin A is an alkaloid that shows various biological activities including strong cytotoxic activity [122]. During the first step, starting