Planta Med 2019; 85(18): 1510
DOI: 10.1055/s-0039-3399951
Main Congress Poster
Poster Session 2
© Georg Thieme Verlag KG Stuttgart · New York

Antiausterity activity against pancreatic cancer cells and antiplasmodial properties of naphthylisoquinoline alkaloids and their analogues

V Maharaj
1   Department of Chemistry, Faculty of Natural and Agricultural Sciences, Institute for Sustainable Malaria Control, University of Pretoria,, Private Bag x20, Hatfield 0028, South Africa
,
SM Kavatsurwa
1   Department of Chemistry, Faculty of Natural and Agricultural Sciences, Institute for Sustainable Malaria Control, University of Pretoria,, Private Bag x20, Hatfield 0028, South Africa
2   Institut für Organische Chemie, Universität Würzburg,, Am Hubland, 97074 Würzburg, Germany
,
W Shamburger
2   Institut für Organische Chemie, Universität Würzburg,, Am Hubland, 97074 Würzburg, Germany
,
P Moyo
3   Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, Institute for Sustainable Malaria Control, University of Pretoria,, Private Bag x20, Hatfield 0028, South Africa
,
R Seupel
2   Institut für Organische Chemie, Universität Würzburg,, Am Hubland, 97074 Würzburg, Germany
,
LM Birkholtz
3   Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, Institute for Sustainable Malaria Control, University of Pretoria,, Private Bag x20, Hatfield 0028, South Africa
,
G Bringmann
2   Institut für Organische Chemie, Universität Würzburg,, Am Hubland, 97074 Würzburg, Germany
,
BK Lombe
2   Institut für Organische Chemie, Universität Würzburg,, Am Hubland, 97074 Würzburg, Germany
,
S Awale
4   Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama,, 2630 Sugitani, Toyama 930-0194, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2019 (online)

 

Cancer and malaria are causes for concern within the global health sector both accounting for millions of fatalities annually. Contributing to this is the reduced survival rate (< 5%) of patients diagnosed with pancreatic cancer and drug resistance in malaria which threatens to further exacerbate the already worrisome situation. These emphasize the need to develop new drugs to combat these diseases. Inspired by the fact that natural products have served as a source of unique privileged chemical scaffolds, we have screened a small library of naphthylisoquinoline alkaloids isolated from Ancistrocladus species from the D.R. Congo for their antiausterity activity against human PANC-1 pancreatic cancer cells and antiplasmodial activity against both intra-erythrocytic asexual and sexual Plasmodium parasites. The compounds showed moderate to strong antiausterity activities at a concentration-dependent manner with their PC50 values ranging from 7.6 to 67.8 μM. New compounds ancistroyafungines B and D were the most potent representatives within this series[ [ 1 ] ]. Eleven out of 30 compounds investigated for their antiplasmodial activity showed good growth-inhibitory effects (IC50 < 1 µM) against both drug sensitive and resistant intra-erythrocytic asexual P. falciparum parasite strains with most promising minimal (10 > R.I. >1) to no cross resistance (R.I. < 1) to chloroquine with selectivity indices of > 10. Jozimine A2 was the most potent agent against P. falciparum gametocyte stages and in blocking exflagellation of microgametes. Our study provides encouraging data for the continued interrogation of naphthylisoquinoline alkaloids in search of novel drugs for the treatment of both cancer and malaria.

 

  • References

  • 1 Kavatsurwa SM, Lombe BK, Feineis D, Dibwe DF, Maharaj V, Awale S, Bringmann G. Ancistroyafungines A-D, 5,8′- and 5,1′-coupled naphthylisoquinoline alkaloids from a Congolese Ancistrocladus species, with antiausterity activities against human PANC-1 pancreatic cancer cells. Fitoterapia 2018; 130: 6-16
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