Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• and breast carcinoma MCF7. In parallel, human skin fibroblasts were used as reference for non-tumor cells and roscovitine (ROSCO), doxorubicin (DOXO) and Taxol as positive controls. For details see: ref. [2] and Supporting Information File 1, Table S1. Compounds 4a–f, 4h, 4i, 4k, 4l, 4o and 4q that

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• ), and interleukin-6 (IL-6) [56][57][58]. The combination of crocins with doxorubicin and curcumin also showed a good anti-inflammation effect [56][59]. Antidepression Alsanie et al. found that the therapeutic effect of C. sativus extract on mild and moderate depressive disorder is comparable to

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• water-soluble hexacarboxylated tribenzotriquinacene derivative (TBTQ-CB6) was synthesized and used as a supramolecular drug carrier to load the model anticancer drugs dimethyl viologen (MV) and doxorubicin (DOX) via host–guest interactions. The drugs could be effectively released by spermine (SM), a

• cancer treatment [1][2]. Many types of chemotherapeutic drugs have been commonly used in clinical practice, including doxorubicin (DOX) [3], chlorambucil [4], oxaliplatin [5], etc. However, the use of most chemotherapeutic agents is often challenged by their poor water solubility and non-selective

• association constant was determined to be Ka = (7.67 ± 0.34) × 104 M−1 by nonlinear curve fitting [33] (Figure 1d). Host–guest complexation of TBTQ-CB6 with doxorubicin (DOX). The host–guest complexation between TBTQ-CB6 and DOX was studied by methods similar to those used for TBTQ-CB6 and MV. The 1H NMR

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

• ]. Ellipticine, the standard drug, displayed an IC50 value of 4.06 μM. The activities against KB and MCF-7 cell lines were evaluated using the resazurin microplate assay [18]. Doxorubicin was used as a standard drug for KB and MCF-7 cell lines and displayed IC50 values of 1.21 and 15.84 μM, respectively

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• ], amyloid-β protein production inhibitory [52], urease inhibitory [53], farnesyl transferase inhibitory (kurasoin A and B) [54][55], antitumor and antibacterial (doxorubicin, olivomycin A, chromomycin A3, carminomycin I, epothilones) [56][57][58] activities. Experimental General information 1Н and 13С NMR

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

• 15b were also active against HCT-116 cells. However, none of the tested compounds was able to inhibit MCF-7 cell proliferation (Figure S1 in Supporting Information File 1). Next, we determined the IC50 of the active compounds against both HCT-116 and T98G cells; we employed doxorubicin as positive

• control. We also investigated the potency of erlotinib hydrochloride, gefitinib, and verubulin against T98G cells, which were the most sensitive to the novel 4-anilinoquinazolines (Figure S2 in Supporting Information File 1). Compared to the reference drug, doxorubicin, derivative 10b showed promising

• inhibition upon exposure to 4-anilinoquinazolines and compounds with the same scaffolds (erlotinib, gefitinib, and verubulin), and to positive control doxorubicin (MTT assay after treatment for 72 h). Supporting Information Supporting Information File 282: Experimental procedures, characterization data

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• doxorubicin hydrochloride was 0.13 μM. Antimicrobial assay Antimicrobial assays were carried out against five bacteria, K. rhizophila ATCC 9341, S. aureus FDA209P JC-1, E. coli NIHJ JC-2, R. solanacearum SUPP1541, and R. radiobacter NBRC 14554, and a yeast C. albicans NBRC 0197 in the same manner as reported

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• [52] was used with commercial nonselective antitumor agent doxorubicin (DOX) as control [53]. The results of antiproliferative in vitro analysis of all tested compounds are shown in Table 4. Among all tested compounds, ketone 3 showed the lowest IC50 value (1.06 μM) towards MDA-MB-231 cells, with

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• 2 weeks. However, this could result in a sustained release over longer time periods which would require further investigation. Doxorubicin release from heparin-containing cryogel microcarriers was investigated by Newland et al. [100]. Highly sulphated heparin was used to exploit electrostatic

• interactions between anionic sulphate groups and the primary amine group present in doxorubicin which confers a positive charge under physiological conditions. This interaction was confirmed by in silico modelling. While the carriers did not show any cytotoxicity, cell viability was reduced in the presence of

• the doxorubicin-loaded cryogels, suggesting delivery of the drug was successful. These cryogels were also injected into mice, adjacent to an orthotopic breast cancer tumour, impeding tumour growth and metastasis. Several groups have reported on the use of composite cryogels for drug delivery, whereby

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• be taken into account that the drug can interfere with the block copolymer aggregation. Alternatively, the use of reactive polymers for the polymerization creates a functional anchor to enable post-functionalization of the PISA nanoparticles with drugs such as doxorubicin [35][36]. In a different

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• fully decorated triazoles 53 (Scheme 18a). A research group reported a novel polymer 56 functionalized by doxorubicin (DOX). To produce this prodrug, cyclooctyne-derivatized doxorubicin 55 was grafted on an azide-functionalized polymer 54. In the final step of the construction of this prodrug, the

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• with a standard drug, doxorubicin, were screened for their cytotoxicity against various cancer lines (Figure 5, Table 3 and Figure S2, in Supporting Information File 1) such as MCF-7 (breast cancer), HeLa (cervical cancer), HEK293 (human embryonic kidney cells), A431 (skin cancer), A549 (lung cancer

• ), and macrophage or immune cell line (RAW 264.7). The cancer cells were treated with increasing concentrations of the carboline derivatives 3ac, 3bc, 3ca, 3ga and doxorubicin (0.1 μM, 0.25 μM, 0.5 μM, 1 μM, 2.5 μM, 5 μM, 10 μM, 25 μM, 50 μM, 100 μM) and incubated for 48 h. Half-maximal inhibitory

• studies show that the γ-carbolines are highly toxic to cancer cells at micromolar concentrations similar to doxorubicin, whereas they are non-cytotoxic (Figure 6) to human macrophages or immune cells. At last, to evaluate cell uptake of the novel γ-carboline for fluorescence imaging, live-cell imaging

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• their LNP formulation to functionalize LNPs with an aptamer specific for the human epidermal growth factor 2 (HER2) receptor. Therein, functionalized LNPs increased siRNA delivery and subsequent sensitivity of the doxorubicin-resistant HER2-positive breast cancer cell lines by ≈2-fold over LNPs with no

• –transferrin increased brain delivery by 2.8-fold compared to liposomes without transferrin in a BBB model and in vivo [15] and further when loaded with the chemotherapeutic agent doxorubicin. They observed increased delivery of this compound and subsequently a significant tumor regression in mouse xenografts

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• approach delivered the desired product in 62% yield after 6 h which reveals the efficiency of microwaves in increasing the yield and reducing the reaction time. The studies for the anticancer activity of the synthesized molecules revealed them to be more potent than the standard doxorubicin against AGS

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• nanoparticles, depending on the degree of substitution. For example, reaction of vicinal diols of dextran with hydrophobic PBA generates boronate esters, which form nanoparticles in water and are capable to host the anticancer drug doxorubicin [27]. In this report, the advantages of the milling process, such as

• in aqueous media, without further functionalization, but can trap apolar molecules in the interior, as was shown in [27] for nanoparticles formed from dextran boronated in bulk. These nanoparticles formed by hydrophobic interactions were capable of solubilizing doxorubicin and liberated the drug

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• cells were seeded in each well of a 96-well culture plate at a density of 2500 cells/well. Meanwhile, the compounds 1–4 and doxorubicin hydrochloride as a positive control were serially diluted 1:3.16 (half-log dilution) by the same medium in a different microtiter plate. After incubating the cell

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• amphotericin B, were 0.31 (against K. rhizophila) and 0.13 (against G. cingulata) μg/mL, respectively. Cytotoxicity assay The cytotoxicity assay was carried out in the same manner as reported previously [49]. The IC50 of the reference drug doxorubicin was 0.13 μM. Structures of pseudosporamide (1) and

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

• , the 4-methoxyphenyl group appeared to enhance the anticancer activity of the bis(2-arylimidazo[1,2-a]pyridin-3-yl) diselenides and selenides. Furthermore, only the compound 2f showed a higher anticancer activity than doxorubicin (DOX), a well-known anthracycline-based anticancer drug. As shown in

• represented as mean ± S.D. values of four samples. *p < 0.05; **p < 0.01 compared to the control. DOX: doxorubicin. The cytotoxic effect of the bis[2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-yl] diselenide 2f on cancer cell lines. Human glioblastoma U251 cells (a) and human malignant meningioma HKBMM cells (b

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• cytotoxic anthraquinone moiety and obtained positive, yet limited, cytotoxic activities [63][64]. Furthermore, a steroidal anti-estrogen–doxorubicin conjugate was synthesized by Hanson, showing a 70-fold increase of activity compared to doxorubicin in inhibiting cell proliferation and promoting cell death

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• containing ʟ-glutamine (product no. 186-02155) supplemented with 10% fetal bovine serum and 0.1 mg/mL gentamicin sulfate. Compounds 1, 2, and doxorubicin as a reference were serially diluted by a factor of 3.16 (half-logarithmic dilution) in a 96-well round-bottom microtiter plate. To each well were seeded

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• on pH-responsive supramolecular self-assemblies by utilizing β-CD-benzimidazole2 (β-CD-BM2) as AB2-type amphiphilic HGCMs for the delivery and controlled release of doxorubicin (DOX). β-CD-BM2 was first synthesized by click reaction (Scheme 1a). β-CD-BM2 formed fan-shaped self-assemblies (FSSAs) at

• -assemblies was driven by the pH-induced dissociation of host–guest interactions between BM and β-CD. Controlled release behaviors of drug-loaded supramolecular self-assemblies β-CD-BM2-based SSAs were used as nanocarriers for drug delivery. Doxorubicin (DOX) was first loaded into FSSAs with a drug-loaded

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

• doxorubicin as cytotoxic drugs to native NPY by using various linker chemistries. However, due to missing hY1R-selectivity and relatively weak antitumor efficacy these conjugates were found unsuitable as PDCs [38]. More recently, further approaches of hY1R-addressing PDCs for therapeutic applications have

• linker cleavage the intracellular activities of 8, i.e., the activities of the linker cleavage product 9, are within an acceptable range, and are comparable or higher than that of some commercially used anticancer compounds (e.g., cisplatin and doxorubicin). Further in vitro cell proliferation and

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

• doxorubicin (formerly known as AEZS-108 or AN-152), in which the superagonist [D-6Lys]-GnRH-I allows the tumor targeting of the traditional chemotherapeutical drug doxorubicin covalently linked via an ester bond [3][10]. However, while in the phase II trial, zoptarelin doxorubicin showed promising antitumor

• activity combined with the lower rate of adverse effects in recurrent endometrial cancers [11], in the phase III study, there was no meaningful difference between the patients treated with zoptarelin doxorubicin or doxorubicin with respect to efficacy of agents and incidence of adverse effects (e.g

• ., cardiac disorders typical for anthracyclines) [12]. The adverse effects were supposed to be related to (i) doxorubicin released early from the conjugate because of the instability of the ester linkage and (ii) [D-6Lys]-GnRH-I induced endocrine side effects [8]. Therefore, recent strategies for the