Biotransformation of 1α,11α-dihydroxyisopimara-8(14),15-diene by Cunninghamella echinulata NRRL 1386 and their neuroprotective activity

Ratchanaporn Chokchaisiri; Waraluck Chaichompoo; Wachirachai Pabuprapap; Oratai Sukcharoen; Jiraporn Tocharus; Lucksagoon Ganranoo; Sareeya Bureekaew; Ek Sangvichien; Apichart Suksamrarn

doi:10.1016/j.bioorg.2021.104799

Biotransformation of 1α,11α-dihydroxyisopimara-8(14),15-diene by Cunninghamella echinulata NRRL 1386 and their neuroprotective activity

Bioorg Chem. 2021 May:110:104799. doi: 10.1016/j.bioorg.2021.104799. Epub 2021 Mar 5.

Authors

Ratchanaporn Chokchaisiri¹, Waraluck Chaichompoo², Wachirachai Pabuprapap², Oratai Sukcharoen³, Jiraporn Tocharus⁴, Lucksagoon Ganranoo⁵, Sareeya Bureekaew⁶, Ek Sangvichien⁷, Apichart Suksamrarn²

Affiliations

¹ Department of Chemistry, School of Science, University of Phayao, Phayao 56000, Thailand. Electronic address: rchokchaisiri@gmail.com.
² Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
³ Department of Biotechnology, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
⁴ Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
⁵ Department of Chemistry, School of Science, University of Phayao, Phayao 56000, Thailand.
⁶ Department of Energy Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC), Wangchan, Rayong 21210, Thailand.
⁷ Department of Biology, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.

PMID: 33730671
DOI: 10.1016/j.bioorg.2021.104799

Abstract

The isopimarane diterpene, 1α,11α-dihydroxyisopimara-8(14),15-diene (1), is the major constituents from the rhizomes of Kaempferia marginata (Zingiberaceae), a Thai medicinal plant. The microbial transformation of parent compound 1 by the fungus Cunninghamella echinulata NRRL 1386 gave five new metabolites, 7α,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (2), 3β,7α,11α-trihydroxy-1-oxoisopimara-8(14),15-diene (3), 7β,11α-dihydroxy-1-oxoisopimara-8(14),15-diene (4), 7α-hydroxy-1,11-dioxoisopimara-8(14),15-diene (5) and 1α,7β,11α-trihydroxyisopimara-8(14),15-diene (6), together with three known metabolites, 7-9. The structures of the new metabolites were elucidated by spectroscopic techniques. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The parent compound 1 and the metabolites have been neuroprotective activities evaluated against Aβ_25-35-induced damage in human neuroblastoma cells (SK-N-SH). Among them, compounds 1-3, 5 and 7-9 had significant neuroprotective activities at a concentration of 2.5 μM. The results demonstrated that these compounds might be worth for further development into therapeutic agents for the treatment of neurodegenerative diseases.

Keywords: Cunninghamella echinulata; Kaempferia marginata; Microbial transformation; Neuroprotective activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / antagonists & inhibitors*
Amyloid beta-Peptides / metabolism
Biotransformation*
Cell Survival / drug effects
Dose-Response Relationship, Drug
Humans
Molecular Structure
Neuroprotective Agents / chemistry
Neuroprotective Agents / isolation & purification
Neuroprotective Agents / pharmacology*
Peptide Fragments / antagonists & inhibitors*
Peptide Fragments / metabolism
Structure-Activity Relationship
Tumor Cells, Cultured
Zingiberaceae / chemistry*

Substances

Amyloid beta-Peptides
Neuroprotective Agents
Peptide Fragments
amyloid beta-protein (25-35)