Synthesis and Cytotoxic Activity of New Vindoline Derivatives Coupled to Natural and Synthetic Pharmacophores

András Keglevich; Leonetta Dányi; Alexandra Rieder; Dorottya Horváth; Áron Szigetvári; Miklós Dékány; Csaba Szántay Jr; Ahmed Dhahir Latif; Attila Hunyadi; István Zupkó; Péter Keglevich; László Hazai

doi:10.3390/molecules25041010

Synthesis and Cytotoxic Activity of New Vindoline Derivatives Coupled to Natural and Synthetic Pharmacophores

Molecules. 2020 Feb 24;25(4):1010. doi: 10.3390/molecules25041010.

Authors

Affiliations

¹ Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Gellért tér 4., Hungary.
² Spectroscopic Research Department, Gedeon Richter Plc., H-1475 Budapest 10, P. O. Box 27, Hungary.
³ Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary.
⁴ Department of Pharmacodynamics and Biopharmacy, Interdisciplinary Excellence Centre, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary.
⁵ Interdisciplinary Centre for Natural Products, University of Szeged, H-6720 Szeged, Eötvös u. 6., Hungary.

Abstract

New Vinca alkaloid derivatives were synthesized to improve the biological activity of the natural alkaloid vindoline. To this end, experiments were performed to link vindoline with various structural units, such as amino acids, a 1,2,3-triazole derivative, morpholine, piperazine and N-methylpiperazine. The structure of the new compounds was characterized by NMR spectroscopy and mass spectrometry (MS). Several compounds exhibited in vitro antiproliferative activity against human gynecological cancer cell lines with IC₅₀ values in the low micromolar concentration range.

Keywords: IC50 values; Vinca alkaloids; anticancer drugs; organic synthesis; pharmacophores; vindoline.

MeSH terms

Amino Acids / chemistry*
Antineoplastic Agents, Phytogenic / chemical synthesis*
Antineoplastic Agents, Phytogenic / pharmacology
Cell Line, Tumor
Cell Survival / drug effects
Chemistry Techniques, Synthetic
Cytotoxins / chemical synthesis*
Cytotoxins / pharmacology
Dose-Response Relationship, Drug
HeLa Cells
Humans
Inhibitory Concentration 50
MCF-7 Cells
Molecular Structure
Morpholines / chemistry*
Piperazines / chemistry*
Structure-Activity Relationship
Triazoles / chemistry*
Vinblastine / analogs & derivatives*
Vinblastine / chemistry

Substances

Amino Acids
Antineoplastic Agents, Phytogenic
Cytotoxins
Morpholines
Piperazines
Triazoles
vindoline
Vinblastine
morpholine