Geopyxins A-E, ent -Kaurane diterpenoids from endolichenic fungal strains geopyxis aff. majalis and Geopyxis sp. AZ0066: Structure-activity relationships of geopyxins and their analogues(1)

E. M Kithsiri Wijeratne, Bharat P. Bashyal, Manping X. Liu, Danilo D. Rocha, G. M Kamal B Gunaherath, Jana M. U'Ren, Malkanthi K. Gunatilaka, A. Elizabeth Arnold, Luke Whitesell, A. A Leslie Gunatilaka

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Four new ent-kaurane diterpenoids, geopyxins A-D (1-4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3. The structures of 1-6 were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher's ester method. Methylation of 1-3, 5, and 6 gave their corresponding methyl esters 7-11. On acetylation, 1 and 7 yielded their corresponding monoacetates 12 and 14 and diacetates 13 and 15. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds 2, 7-10, 12, 14, and 15 showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds 7-9, 14, and 15 were found to activate the heat-shock response at similar concentrations. From a preliminary structure-activity perspective, the electrophilic α,β-unsaturated ketone carbonyl motif present in all compounds except 6 and 11 was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalJournal of Natural Products
Volume75
Issue number3
DOIs
StatePublished - Mar 23 2012

Fingerprint

Kaurane Diterpenes
Diterpenes
Structure-Activity Relationship
Shock
Esters
Hot Temperature
Heat-Shock Response
Lichens
Acetylation
Ketones
Methylation
Fungi
Cytotoxicity
Cell Line
Chemical activation
Cells
Neoplasms

ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Geopyxins A-E, ent -Kaurane diterpenoids from endolichenic fungal strains geopyxis aff. majalis and Geopyxis sp. AZ0066 : Structure-activity relationships of geopyxins and their analogues(1). / Wijeratne, E. M Kithsiri; Bashyal, Bharat P.; Liu, Manping X.; Rocha, Danilo D.; Gunaherath, G. M Kamal B; U'Ren, Jana M.; Gunatilaka, Malkanthi K.; Arnold, A. Elizabeth; Whitesell, Luke; Gunatilaka, A. A Leslie.

In: Journal of Natural Products, Vol. 75, No. 3, 23.03.2012, p. 361-369.

Research output: Contribution to journalArticle

Wijeratne, E. M Kithsiri ; Bashyal, Bharat P. ; Liu, Manping X. ; Rocha, Danilo D. ; Gunaherath, G. M Kamal B ; U'Ren, Jana M. ; Gunatilaka, Malkanthi K. ; Arnold, A. Elizabeth ; Whitesell, Luke ; Gunatilaka, A. A Leslie. / Geopyxins A-E, ent -Kaurane diterpenoids from endolichenic fungal strains geopyxis aff. majalis and Geopyxis sp. AZ0066 : Structure-activity relationships of geopyxins and their analogues(1). In: Journal of Natural Products. 2012 ; Vol. 75, No. 3. pp. 361-369.
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