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Article

Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection

1
Department of Chemistry, NAmur MEdicine and Drug Innovation Center (NAMEDIC-NARILIS), University of Namur, 61 rue de Bruxelles, B-5000 Namur, Belgium
2
URBC—NARILIS, University of Namur, 61 rue de Bruxelles, B-5000 Namur, Belgium
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1491; https://doi.org/10.3390/ijms20061491
Received: 27 February 2019 / Revised: 20 March 2019 / Accepted: 21 March 2019 / Published: 25 March 2019
Harmine is a natural β-carboline compound showing several biological activities, including antiproliferative properties, but this soluble natural molecule lacks selectivity. Harmine derivatives were reported to overcome this problem, but they are usually poorly soluble. Here, we designed and synthesized a new 2, 7, 9-trisubstituted molecule (1-methyl-7-(3-methylbutoxy)-9-propyl-2-[(pyridin-2-yl)methyl]-9H-pyrido[3,4-b]indol-2-ium bromide) with a solubility of 1.87 ± 0.07 mg/mL in a simulated injection vehicle. This compound is stable for at least 72 h in acidic and physiological conditions (pH 1.1 and 7.4) as well as in a simulated injection vehicle (physiological liquid + 0.1% Tween80®). Solubility in those media is 1.06 ± 0.08 mg/mL and 1.62 ± 0.13 mg/mL at pH 7.4 and 1. The synthesized molecule displays a significant activity on five different cancer cell lines (IC50 range from 0.2 to 2 µM on A549, MDA-MB-231, PANC-1, T98G and Hs683 cell lines). This compound is also more active on cancer cells (MDA-MB-231) than on normal cells (MCF-10a) at IC50 concentrations. Due to its high activity at low concentration, such solubility values should be sufficient for further in vivo antitumoral activity evaluation via intravenous injection. View Full-Text
Keywords: antiproliferative activity; harmine derivative; IV injection; mechanosynthesis antiproliferative activity; harmine derivative; IV injection; mechanosynthesis
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MDPI and ACS Style

Marx, S.; Bodart, L.; Tumanov, N.; Wouters, J. Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection. Int. J. Mol. Sci. 2019, 20, 1491. https://doi.org/10.3390/ijms20061491

AMA Style

Marx S, Bodart L, Tumanov N, Wouters J. Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection. International Journal of Molecular Sciences. 2019; 20(6):1491. https://doi.org/10.3390/ijms20061491

Chicago/Turabian Style

Marx, Sébastien, Laurie Bodart, Nikolay Tumanov, and Johan Wouters. 2019. "Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection" International Journal of Molecular Sciences 20, no. 6: 1491. https://doi.org/10.3390/ijms20061491

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