Verbascoside, synthetic derivatives and other glycosides from Argentinian native plant species as potential antitumoral agents

Abstract

A phytochemical study was performed on three native plant species from the central-western zone of Argentina: Buddleja cordobensis Grisebach, Baccharis salicina Torr. & A. Gray and Nepeta cataria L. We could obtain verbascoside (1) from B. cordobensis. From N. cataria, we could obtain 1, 5, 9-epi-deoxyloganic acid (2) L. Finally, we could isolate 2-β-(L-rhamnopyranosyl)-3-angeloyloxy-15-acetyloxy-7,13(14)-E-dien-ent-labdane (3) and 2-β-(L-rhamnopyranosyl)-3-α-angeloyloxy-15-hydroxy-7,13(14)-E-dien-ent-labdane (4) from B. salicina. Moreover, three derivatives from 1, and one semi-synthetic derivative from 2, were prepared. PCR reaction was used to analyse the activity against DNA polymerase and cell culture to determine cytotoxicity and antitumoral activity. Verbascoside (1) was strongly active in the nanomolar scale (IC₅₀ = 356 nM) against DNA polymerization. Moreover, verbascoside was also strongly active in the nanomolar scale against human melanoma cell line (IC₅₀ = 256 nM) and human colorectal cell line (IC₅₀ = 320 nM). Furthermore, derivatives 6 and 7 were cytotoxic against both cancer cell lines.

GRAPHICAL ABSTRACT

Keywords:

• Glycosides
• DNA polymerase
• Cancer cell lines
• Antitumoral agents
• Natural Products

Acknowledgments

These subsidies are gratefully acknowledged. E. Bruna-Haupt thanks CONICET for a doctoral grant. H. Garro thanks Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario for postdoctoral position. In addition, we want to thank to Dra. C. García and Prof. V. Martín from IUBO (Spain) for their help in the use of HRMS; and Bioq. Joaquín Morillas and Dr. G. Labadie for their help. We wish specially thank to Drs. L. Mascotti and M. Juri-Ayub for DNA material gently provided. We appreciate language revision of the manuscript by staff from the “Instituto de Lenguas, Universidad Nacional de San Luis”.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by UNSL (PROICO 02-2516), Agencia Nacional de Promoción Científica y Tecnológica (PICT 2017-0785), CONICET (PIP 090-2015) and Alexander von Humboldt Foundation.