Total synthesis of inubosin B

Hamissa, Mohamed Farouk; Niederhafner, Petr; Šafařík, Martin; Telus, Marta; Kolářová, Lenka; Koutná, Leah; Šestáková, Hana; Souček, Radko; Šebestı́k, Jaroslav

doi:10.1016/j.tetlet.2020.152641

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…Inubusine B ( 7 ), the naturally occurring acridine alkaloid, has been isolated from extracts of a culture of Streptomyces sp. IFM 11440 [ 12 , 13 ]. Inubusine B ( 7 ) was recently synthetized and displayed higher levels of induce neurogenesis activity [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Novel 3,9-Disubstituted Acridines with Strong Inhibition Activity against Topoisomerase I: Synthesis, Biological Evaluation and Molecular Docking Study

et al. 2023

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A series of novel 3,9-disubstituted acridines were synthesized and their biological potential was investigated. The synthetic plan consists of eight reaction steps, which produce the final products, derivatives 17a–17j, in a moderate yield. The principles of cheminformatics and computational chemistry were applied in order to study the relationship between the physicochemical properties of the 3,9-disubstituted acridines and their biological activity at a cellular and molecular level. The selected 3,9-disubstituted acridine derivatives were studied in the presence of DNA using spectroscopic (UV-Vis, circular dichroism, and thermal denaturation) and electrophoretic (nuclease activity, relaxation and unwinding assays for topoisomerase I and decatenation assay for topoisomerase IIα) methods. Binding constants (2.81–9.03 × 104 M−1) were calculated for the derivatives from the results of the absorption titration spectra. The derivatives were found to have caused the inhibition of both topoisomerase I and topoisomerase IIα. Molecular docking simulations suggested a different way in which the acridines 17a–17j can interact with topoisomerase I versus topoisomerase IIα. A strong correlation between the lipophilicity of the derivatives and their ability to stabilize the intercalation complex was identified for all of the studied agents. Acridines 17a–17j were also subjected to in vitro screening conducted by the Developmental Therapeutic Program of the National Cancer Institute (NCI) against a panel of 60 cancer cell lines. The strongest biological activity was displayed by aniline acridine 17a (MCF7–GI50 18.6 nM) and N,N-dimethylaniline acridine 17b (SR–GI50 38.0 nM). The relationship between the cytostatic activity of the most active substances (derivatives 17a, 17b, and 17e–17h) and their values of KB, LogP, ΔS°, and δ was also investigated. Due to the fact that a significant correlation was only found in the case of charge density, δ, it is possible to assume that the cytostatic effect might be dependent upon the structural specificity of the acridine derivatives.

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Section: Introductionmentioning

confidence: 99%

“…IFM 11440 [ 12 , 13 ]. Inubusine B ( 7 ) was recently synthetized and displayed higher levels of induce neurogenesis activity [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Novel 3,9-Disubstituted Acridines with Strong Inhibition Activity against Topoisomerase I: Synthesis, Biological Evaluation and Molecular Docking Study

et al. 2023

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“…Recently, the total synthesis of inubosine B 6 , an acridine alkaloid that initiates neuroregeneration, has been reported ( Figure 1 ) [ 10 ]. Antimicrobial properties are another important category of biological activity displayed by acridine derivatives [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes

et al. 2021

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A novel series of proflavine ureas, derivatives 11a–11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI50 values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b–0.44 μM, phenyl 11c–0.23 μM, phenylethyl 11f–0.35 μM and hexyl 11j–0.36 μM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.

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Neutral and charged forms of inubosin B in aqueous solutions at different pH and on the surface of Ag nanoparticles

Hamissa

Niederhafner

Šestáková

et al. 2022

Journal of Molecular Structure

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Total synthesis of inubosin B

Cited by 3 publications

References 30 publications

Novel 3,9-Disubstituted Acridines with Strong Inhibition Activity against Topoisomerase I: Synthesis, Biological Evaluation and Molecular Docking Study

Novel 3,9-Disubstituted Acridines with Strong Inhibition Activity against Topoisomerase I: Synthesis, Biological Evaluation and Molecular Docking Study

Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes

Neutral and charged forms of inubosin B in aqueous solutions at different pH and on the surface of Ag nanoparticles

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