Antiplasmodial and Cytotoxic Cytochalasins from an Endophytic Fungus, Nemania sp. UM10M, Isolated from a Diseased Torreya taxifolia Leaf

Mallika Kumarihamy; Daneel Ferreira; Edward M Croom Jr; Rajnish Sahu; Babu L Tekwani; Stephen O Duke; Shabana Khan; Natascha Techen; N P Dhammika Nanayakkara

doi:10.3390/molecules24040777

Antiplasmodial and Cytotoxic Cytochalasins from an Endophytic Fungus, Nemania sp. UM10M, Isolated from a Diseased Torreya taxifolia Leaf

Molecules. 2019 Feb 21;24(4):777. doi: 10.3390/molecules24040777.

Authors

Mallika Kumarihamy^{1

2}, Daneel Ferreira³, Edward M Croom Jr⁴, Rajnish Sahu⁵, Babu L Tekwani⁶, Stephen O Duke⁷, Shabana Khan^{8

9}, Natascha Techen¹⁰, N P Dhammika Nanayakkara¹¹

Affiliations

¹ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. mkumarih@olemiss.edu.
² Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. mkumarih@olemiss.edu.
³ Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. dferreir@olemiss.edu.
⁴ Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. emcroom@olemiss.edu.
⁵ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. rsahu@alasu.edu.
⁶ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. btekwani@southenresearch.org.
⁷ Natural Products Utilization Research Unit, USDA-ARS, University, MS 38677, USA. stephen.duke@ars.usda.gov.
⁸ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. skhan@olemiss.edu.
⁹ Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. skhan@olemiss.edu.
¹⁰ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. ntechen@olemiss.edu.
¹¹ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. dhammika@olemiss.edu.

Abstract

Bioassay-guided fractionation of an EtOAc extract of the broth of the endophytic fungus Nemania sp. UM10M (Xylariaceae) isolated from a diseased Torreya taxifolia leaf afforded three known cytochalasins, 19,20-epoxycytochalasins C (1) and D (2), and 18-deoxy-19,20-epoxy-cytochalasin C (3). All three compounds showed potent in vitro antiplasmodial activity and phytotoxicity with no cytotoxicity to Vero cells. These compounds exhibited moderate to weak cytotoxicity to some of the cell lines of a panel of solid tumor (SK-MEL, KB, BT-549, and SK-OV-3) and kidney epithelial cells (LLC-PK₁₁). Evaluation of in vivo antimalarial activity of 19,20-epoxycytochalasin C (1) in a mouse model at 100 mg/kg dose showed that this compound had weak suppressive antiplasmodial activity and was toxic to animals.

Keywords: Nemania; Torreya taxifolia; Xylariaceae; cytochalasins; cytotoxicity; malaria; phytotoxicity; plant pathogenic and endophytic fungi.

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Antiprotozoal Agents / chemistry
Antiprotozoal Agents / isolation & purification
Antiprotozoal Agents / pharmacology*
Cell Line
Cell Line, Tumor
Cell Survival / drug effects
Chlorocebus aethiops
Cytochalasins / chemistry
Cytochalasins / isolation & purification
Cytochalasins / pharmacology*
Endophytes / chemistry
Epithelial Cells / cytology
Epithelial Cells / drug effects
Humans
Malaria / drug therapy*
Malaria / mortality
Malaria / parasitology
Male
Mice
Plant Leaves / microbiology
Plasmodium berghei / drug effects
Plasmodium berghei / growth & development
Survival Analysis
Taxaceae / microbiology*
Vero Cells
Xylariales / chemistry*

Substances

Antineoplastic Agents
Antiprotozoal Agents
Cytochalasins