Penochalasin K, a new unusual chaetoglobosin from the mangrove endophytic fungus Penicillium chrysogenum V11 and its effective semi-synthesis

Fitoterapia. 2017 Nov:123:23-28. doi: 10.1016/j.fitote.2017.09.016. Epub 2017 Sep 27.

Abstract

A new chaetoglobosin, penochalasin K (1) bearing an unusual six-cyclic 6/5/6/5/6/13 fused ring system, along with the known analogues, chaetoglobosin C (2), penochalasin I (3), and chaetoglobosin A (4) were isolated from the solid culture of the mangrove endophytic fungus Penicillium chrysogenum V11. Their structures were elucidated by 1D, 2D NMR spectroscopic analysis and high resolution mass spectroscopic data. The absolute configuration of compound 1 was determined by comparing the theoretical and experimental electronic circular dichroism curves. Compound 1 displayed significant inhibitory activities against Colletotrichum gloeosporioides and Rhizoctonia solani (MICs=6.13, 12.26μM, respectively), which was better than those of carbendazim, and exhibited potent cytotoxicity against MDA-MB-435, SGC-7901 and A549 cells (IC50<10μM). An effective biomimetic transformation of chaetoglobosin C (2)/chaetoglobosin A (4) into penochalasin K (1)/penochalasin I (3) was developed, which provided a simple method for the semi-synthesis of chaetoglobosins with a six-cyclic 6/5/6/5/6/13 fused system formed by the connectivity of C-5 and C-2' from their corresponding epoxide analogues.

Keywords: Antifungal activity; Chaetoglobosin; Cytotoxicity; Mangrove endophytic fungus; Penicillium chrysogenum.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification
  • Cell Line, Tumor
  • Colletotrichum / drug effects
  • Endophytes / chemistry
  • Humans
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / isolation & purification
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Penicillium chrysogenum / chemistry*
  • Rhizoctonia / drug effects

Substances

  • Antifungal Agents
  • Indole Alkaloids
  • chaetoglobosins