3D-QSAR, design, synthesis and characterization of trisubstituted harmine derivatives with in vitro antiproliferative properties

European Journal of Medicinal Chemistry
Céline MeinguetJohan Wouters

Abstract

Apolar trisubstituted derivatives of harmine show high antiproliferative activity on diverse cancer cell lines. However, these molecules present a poor solubility making these compounds poorly bioavailable. Here, new compounds were synthesized in order to improve solubility while retaining antiproliferative activity. First, polar substituents have shown a higher solubility but a loss of antiproliferative activity. Second, a Comparative Molecular Field Analysis (CoMFA) model was developed, guiding the design and synthesis of eight new compounds. Characterization has underlined the in vitro antiproliferative character of these compounds on five cancerous cell lines, combining with a high solubility at physiological pH, making these molecules druggable. Moreover, targeting glioma treatment, human intestinal absorption and blood brain penetration have been calculated, showing high absorption and penetration properties.

References

Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·S R Kimball
Oct 29, 2000·Journal of Medicinal Chemistry·W J EganJ J Baldwin
Mar 29, 2001·Journal of Pharmacological and Toxicological Methods·C A Lipinski
Dec 25, 2010·Bioorganic & Medicinal Chemistry·J ReniersJ Wouters
Jul 6, 2011·Journal of Medicinal Chemistry·Eduard DolusićRaphaël Frédérick
Dec 8, 2011·Hepatobiliary & Pancreatic Diseases International : HBPD INT·Ming-Rong CaoJian-Wei Jiang
Jul 10, 2012·Journal of Medicinal Chemistry·Raphaël FrédérickJohan Wouters
Jul 26, 2012·ISRN Pharmaceutics·Ketan T SavjaniJignasa K Savjani
Jan 8, 2013·European Journal of Medicinal Chemistry·Rihui CaoLiqin Qiu

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Citations

Mar 31, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Insaf FilaliJalloul Bouajila
Jun 17, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Céline MeinguetJohan Wouters
Dec 20, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ji Hye HanWook Kim
Jan 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elise PiersonJohan Wouters
Apr 3, 2019·International Journal of Molecular Sciences·Sébastien MarxJohan Wouters
Nov 19, 2020·Archives of Pharmacal Research·Liang ZhangShenglan Yu
Apr 4, 2021·International Journal of Molecular Sciences·Kyeongmin KimBuHyun Youn

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