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

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

• photophysical and photochemical characterizations of this Ru(II)–calixarene conjugate as well as the study of its photoreactivity in the presence of guanosine monophosphate have been achieved. The results show that the ruthenium complex should be able to perform efficiently its photoinduced cytotoxic activity

• cytotoxic activity, once incorporated into targeted cancer cells thanks to the multivalent platform. In cellulo studies are currently under investigation and will be reported in the near future. Experimental General: All the solvents and reagents for the syntheses were at least reagent grade quality and

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929

• (KB3.1), colon carcinoma cells (HCT-116), and glioblastoma (U87MG). It exhibited cytotoxic activity with IC50 values of 3.1 and 1.5 µM against L929 and KB3.1 cell cultures, respectively, while it was not active against the other cell lines according to the limits of the National Cancer Institute (active

• activities on a Berthold Technologies Centro XS3 Microplate Luminometer as indicators of viral genome replication and cell viability, respectively, as previously described [18]. Cytotoxic activity The cytotoxicity was evaluated by measuring the effect produced on cell morphology including the nuclei and cell

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• composites loaded with quercetin may show improved cytotoxic activity towards some human breast cancer cell lines [32], likely due to a synergistic action between the polyphenol nutraceutic guest molecule and triazole derivatives coming from the progressive disgregation of the co-polymer carrier. From the

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

• ][40]. The benzoyl nitrogen mustard (BAM) to the formyl end of the distamycin acts as an alkylating moiety whereas the distamycin framework acts as a DNA binding domain. Therefore, due to the installation of the alkylating moiety, TAM has higher cytotoxic activity in comparison to distamycin, and shows

• structure–activity relationship. It has been observed that the number and position of pyrrole rings are crucial for antileukemic activity. The presence of pyrrole rings close to the alkylating BAM moiety is responsible for better cytotoxic activity both in vitro and in vivo, whereas a pyrazole ring in close

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

• rationally installed taking into consideration the final derivative of the cytotoxic agent to retain the original cytotoxic activity. The sections below summarize the basic design principles of peptide–drug conjugates to selectively target the malignant cells. Selecting the proper tumor-targeting peptide to

• -amino group of the D-Lys side chain of the peptide D-Lys6-LHRH. Notably, both conjugates fully preserved the cytotoxic activity of the parent drugs, DOX or 2-pyrrolino-DOX, respectively, in vitro and also retained the high binding affinity of their peptide carrier to receptors for LHRH on rat pituitary

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

• % (3) and 53% (6)), demonstrating that all measured compounds displayed an in vitro cytotoxic activity. Nevertheless, the replacement of 6Asp by D-Asp, D-Glu or D-Trp led to a decreased cytostatic effect on the estimated cancer cell lines. Considering the determined IC50 values, no relevant differences

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

• active zwitterionic species via an o-QM intermediate. Dimmock et al. subsequently examined the cytotoxic activity of phenolic azobenzene Mannich bases [92]. Correlations were found between structures and activities against murine P388DI and L1210 cells, human T-lymphocyte cell lines and, in some cases

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

• ). Interestingly, high yields of the corresponding pyrazolo[3,4-b]pyridines 34 were obtained when reactions were carried under solvent-free microwave irradiation. The synthesized pyrazolo[3,4-b]pyridines have shown potential cytotoxic activity against cervical HeLa and prostate DU 205 cancer cell lines. A similar

• screened for their cytotoxic activity against human colon carcinoma (Colo-205) cell lines (Scheme 35). Buriol et al. [92] described the reaction of 5-aminopyrazole 16 with 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones 129 to yield pyrazolo[1,5-a]pyrimidine derivatives 130 in acetic acid and ethanol using

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• -5,6-dihydro-2H-pyran-2-one (9) and 6-nonyl-2H-pyran-2-one (17). Volatiles from Daldinia clavata MUCL 47436. 13C NMR data (chemical shifts in ppm) for 11a–d (125 MHz, C6D6). In vitro antibacterial, antifungal and cytotoxic activity of compounds 9, 14 and 17 in comparison with positive controls

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• oxoisoaporphine alkaloids and the isomers 18 and 19 showed significant cytotoxic activity. IC50 values of alkaloid 3 and of compounds 18 and 19 are ranging from 3–6 µM. Very strong cytotoxicity was determined for 6-O-demethylmenisporphine (4) with an IC50 value of 0.06 µM and for dauriporphinoline (5) with 0.23

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

• cytotoxic activity toward lymphoma cells, resulting active at a very low micromolar range [101]. With the aim to activate the human immune system against self-tumor cells, Schlecht and co-workers designed the synthesis of AuNPs functionalized with Mucin1(MUC1)-glycopeptide antigens [102]. Mucins are a

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

• keto-oximes 179 and 2-amino derivatives 180 are β2-adrenergic agonists tested for bronchodilating activity. The pterosin family are sesquiterpenoids naturally occurring in bracken fern (Pteridium aquilinum), some of them exhibit antibacterial and cytotoxic activity. A practical synthesis of pterosin A

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

• calorimetry (DSC). The prepared compounds were also screened for their cytotoxic activity against five cell lines. It was observed that the lipoconjugates of caffeic acid, sinapic acid, ferulic acid, and coumaric acid displayed anticancer and anti-oxidant properties. The anticancer properties of these

• due to different media used for the assays; the DPPH assay is conducted in a polar medium but the linoleic acid oxidation study is conducted in a non-polar environment. Cytotoxic activity As there were studies reported on the cytotoxicity of phenolic lipids, we have further screened the prepared