Cytotoxic 1,3-Thiazole and 1,2,4-Thiadiazole Alkaloids from Penicillium oxalicum: Structural Elucidation and Total Synthesis

Molecules. 2016 Feb 26;21(3):232. doi: 10.3390/molecules21030232.

Abstract

Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target.

Keywords: Penicillium oxalicum; alkaloids; cytotoxicity; structure elucidation; total synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Cytotoxins / chemical synthesis*
  • Cytotoxins / isolation & purification
  • Cytotoxins / pharmacology
  • Gene Expression
  • Grasshoppers / microbiology
  • Humans
  • Molecular Structure
  • Penicillium / chemistry*
  • Penicillium / isolation & purification
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Thiadiazoles / chemical synthesis*
  • Thiadiazoles / isolation & purification
  • Thiadiazoles / pharmacology
  • Thiazoles / chemical synthesis*
  • Thiazoles / isolation & purification
  • Thiazoles / pharmacology

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Cytotoxins
  • Thiadiazoles
  • Thiazoles
  • Proto-Oncogene Proteins c-akt