Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• , and furthermore in vivo antitumoral and antimetastatic efficacy in early and late-stage colon cancer models and biodistribution after single dose oral administration. This study was carried out to further elucidate oral camptothecin (CPT)-loaded amphiphilic cyclodextrin nanoparticles for the local

• cancer; camptothecin; 3D spheroid; cyclodextrin; oral nanoparticle; release kinetics; Introduction Cancer is still one of the most common, highly variable and fatal diseases worldwide. Therefore, studies are continuing to develop effective/innovative and more flexible treatments for various types of

• is possible, chemotherapeutic treatment is still one of the most researched approaches in terms of tumor recurrence and the progression of the disease. In CRC chemotherapy, the most common approach is mainly an intravenous administration of anticancer drugs such as camptothecin (CPT) analogs

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• alcohol 56, which was dehydroxylated to the diastereomeric cations VIII and IX. Friedel–Crafts reaction gave diastereomeric lactones 57 and 58. The major diastereomer 58 could be converted to the complex polyphenol (−)-hopeanol (59) in seven further steps. (+)-Camptothecin In the formal synthesis of the

• pentacyclic, antiproliferative quinoline alkaloid camptothecin (65), Peters et al. used an α-ketoester moiety in an auxiliary controlled approach towards the only stereogenic center present in the natural product (Scheme 10) [25]. First, the ketoacid 60 was esterified with 8-phenylmenthol (61) to yield the α

• -ketoester 62, followed by nucleophilic addition of isopropenylmagnesium bromide to give α-hydroxyester 63 in excellent yield and diastereoselectivity. Eight additional steps gave the bicyclic compound 64 which was already known from previous camptothecin syntheses. Isoretronecanol The α-ketoester moiety can

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

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• : novel MCR as key step in total synthesis of (+)-20S-camptothecin Another typical example for the simplification of a complex chemical synthesis [2][3] is the total synthesis of the extremely potent antitumor agent (+)-20S-camptothecin (3), which has been a highly effective agent for decades now. This

• for fair cost assessment of complex chemical syntheses. Fragment linking reactions, and an ecteinascidin-743 total syntheses including an Ugi reaction, as well as a 20S-camptothecin total synthesis based on a 4CR specifically generated for this purpose, were discussed. This demonstrates the high

• -camptothecin (3) total synthesis. Overall yields yoa and synthesis efficiency Effsyn.

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• in one operational step. The tricyclic indolizinone scaffold is abundantly present in natural products, as, e.g., in the pharmacologically relevant mappicine [23][24], camptothecin [25][26], 10-hydroxycamptothecin and topotecan [27][28] (Figure 1). In 2012, Park and co-workers reported a RhIII

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• published by Cook [76]. The authors also further establish the immediate value of the procedure to LSF by exploring SAR of camptothecin, a molecule identified as an anticancer drug candidate. The authors selectively manipulated the C-7 position, which has been shown to improve efficacy when alkylated

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

• anticancer drugs utilized to treat malignancies at the moment. Among this large pool of cytotoxic drugs, an array of them has been utilized as toxic warheads in PDCs and five representative examples are gemcitabine, doxorubicin, daunorubicin, paclitaxel and camptothecin (Figure 4). The main drawback of these

• [82], whereas gemcitabine [83], camptothecin [84] and paclitaxel [85] function through different mechanisms. The selected drug must comply with certain design principles in order to serve as an appealing candidate for PDCs. The selected drug must be amenable to the linker chemistry. It must bear an

• of other types of cancers (breast cancer, bladder cancer, Kaposi's sarcoma) in combination with other anti-cancer agents. Camptothecin (CPT): Camptothecin is a cytotoxic alkaloid collected from extraction of the bark and stem of the Chinese tree ‘Camptotheca acuminata’. It was first isolated and

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• ]. Utilizing these reagents, we have successfully synthesized a wide variety of bioactive organofluorine compounds [24][25][26][27][28][29][30] including fluorinated thalidomide (antitumor) [24], fluorinated donepezil (cholinesterase inhibitor) [25], and fluorinated camptothecin (anticancer) [26]. During our

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• to involve 9 in reactions with HPA. Notably, due to its non-planar tetracyclic character, the hexahydropyrrolo[1,2-b]isoquinolone fused with benzene scaffold (present in 10) clearly appears related to (though topologically distinct from) the natural and synthetic camptothecin-like topoisomerase

• , in competition with direct albeit slow conversion 13e → anti-10e (Scheme 5). We mentioned that tetracyclic compounds 10 carry resemblance to natural as well as synthetic camptothecin-like topoisomerase inhibitors (vide supra). Compounds 10 are endowed with HPA-derived carboxylic acid functionality

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• 10.3762/bjoc.11.22 Abstract Background: The aim of this study was to design and evaluate hybrid cyclodextrin (CD) nanocapsules intended for the oral delivery of the anticancer agent camptothecin (CPT) in order to maintain drug stability in the body and to improve its eventual bioavailability. For this

• as CPT which may contribute to patient quality of life and drug efficacy in cancer therapy. Keywords: amphiphilic cyclodextrin; camptothecin; core-shell; nanocapsule; oral chemotherapy; Introduction Cancer is one of the major fatal diseases in the world and causes abnormal growth of cells spreading

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

• , ICMPE, CNRS and University Paris Est, 2 rue Henri Dunant, 94320 Thiais, France 10.3762/bjoc.11.14 Abstract Novel (S)-camptothecin–dextran polymers were obtained by “click” grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were

• prepared with a degree of substitution of (S)-camptothecin between 3.1 and 10.2%. The binding properties with β-cyclodextrin and β-cyclodextrin polymers were measured by isothermal titration calorimetry and fluorescence spectroscopy, showing no binding with β-cyclodextrin but high binding with β

• -cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin–dextran polymers and the β-cyclodextrin polymers. Keywords: (S)-camptothecin; cyclodextrins; fluorescence; nanoparticles; ITC; Introduction Cancer remains to be the major cause of mortality in

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• ][27], only two survivin transcriptional inhibitors (e. g. YM155, terameprocol) are in development or in clinical trials [28][29]. Recently, FL188, a camptothecin analog, has been described to inhibit survivin promoter activity and inhibits the expression of cancer-associated survival genes (Mcl-1

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• . synthesized maleimide derivatives of doxorubicin and camptothecin. After intravenous administration these designed anticancer drugs bind rapidly to circulating albumin [17][18][19]. Endogenous albumin could be seen as a drug carrier, as it accumulates in solid tumors according to the pathophysiology of tumor

Topochemical control of the photodimerization of aromatic compounds by γ-cyclodextrin thioethers in aqueous solution

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1858–1866, doi:10.3762/bjoc.9.217

• , which are able to solubilize hydrophobic, nearly insoluble guest molecules, such as camptothecin [20], 1,4-dihydroxyanthraquinone [21], betulin [22], benzene and cyclohexane derivatives [23], and even C60 [24] in water. Furthermore, their respective γ-CD thioethers form highly water-soluble 1:2

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• incorporation of camptothecin in cyclodextrin nanosponges. The anti-tumour activity of camptothecin has been extensively investigated in both hematological and solid malignancies; however, its use is still limited due to its poor solubility and high chemical instability since the lactone ring of the molecule is

• very susceptible to hydrolysis under physiological conditions. The encapsulation of camptothecin in nanosponges was used to prolong the shelf life and release of the drug [41]. The nanosponges solubilised large amounts of the drug and protected the lactone ring from opening due to its high inclusion

• abilities, thereby increasing stability. Three types of nanosponges, i.e., β-CD-1/2 nanosponges, β-CD-1/4 nanosponges and β-CD-1/8 nanosponges, characterised by an increasing cross-linker/β-CD molar ratio, have been used as delivery systems for camptothecin. All proved to solubilise camptothecin, thereby

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• membrane-permeable phalloidin derivatives appeared shrunken and developed blebs, as described for cells undergoing apoptosis. Treatment with annexin followed by flow cytometric analysis showed a fluorescence distribution typical for apoptosis and similar to that induced by camptothecin. Cells treated with

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• methods for the preparation of quinoline-4-carbaldehyde [12][13][14][15][16][17][18][19][20][21][22][23][24], only a few methods [6][9] are available for the preparation of 3-methylquinoline-4-carbaldehyde derivatives. In connection with the synthesis of camptothecin, we needed a general, high-yielding

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• ), electronic transmission images (TEM), UV–vis and X-ray analysis, setting a pore diameter of 1.9 ± 0.1 nm, a volume of 0.248 cm−3∙g−1 and a surface area of 621.19 m2∙g−1. The nanoparticles, which contain 2.4% by weight of azobenzene, are treated with camptothecin (CPT), a drug used in the treatment of cancer

• released molecules can be controlled depending of the light intensity and irradiation time. On the other hand, the camptothecin, in the absence of light, stays inside the nanoparticles and the cells remain intact. Control experiments with cells lacking the nanoparticles revealed that irradiation at 413 nm

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• cyanopyridones 39b instead. In keeping with a principle introduced during our work on camptothecin [81][82][83], the five-membered ring of 36 was imagined to result upon acid treatment of 40 (Scheme 8) [84], which in turn could be assembled by using the chemistry of Scheme 8 on substrate 41, provided that the

• properties of topopyrones are sufficiently interesting that a number of groups embarked on a total synthesis [94][95][96]. Our own involvement in this area was motivated by an interest in topoisomerase-I inhibitors, which are important antineoplastic resources [97], the archetype of which is camptothecin [81

• reflected a desire to illustrate applications of the new methodology to the synthesis of interesting natural products. The linearly fused topopyrones B and D are especially potent, and indeed, the activity of 53 against topo-I appears to be comparable to that of camptothecin [90][91][100][101]. Accordingly

Efficient synthesis of 5-substituted 2-aryl- 6-cyanoindolizines via nucleophilic substitution reactions

• Eugene V. Babaev,
• Natalya I. Vasilevich and
• Anna S. Ivushkina

Beilstein J. Org. Chem. 2005, 1, No. 9, doi:10.1186/1860-5397-1-9

• natural alkaloids contain in their structure a saturated (swainsonine) or aromatic (camptothecin) indolizine moiety. While the chemistry of indolizines has been widely investigated[1] the chemistry of 5-substituted indolizines remains very poor because there are only a few reliable ways for their