Prospecting Anticancer Compounds in Actinomycetes Recovered from the Sediments of Saint Peter and Saint Paul's Archipelago, Brazil

Chem Biodivers. 2016 Sep;13(9):1149-1157. doi: 10.1002/cbdv.201500514. Epub 2016 Sep 10.

Abstract

Saint Peter and Saint Paul's Archipelago is a collection of 15 islets and rocks remotely located in the equatorial Atlantic Ocean. In this particular site, the present project intended to assess the biodiversity and biotechnological potential of bacteria from the actinomycete group. This study presents the first results of this assessment. From 21 sediment samples, 268 strains were isolated and codified as BRA followed by three numbers. Of those, 94 strains were grown in liquid media and submitted to chemical extractions with AcOEt (A), BuOH (B), and MeOH (M). A total of 224 extracts were screened for their cytotoxic activity and 41 were significantly active against HCT-116 cancer cells. The obtained IC50 values ranged from 0.04 to 31.55 μg/ml. The HR-LC/MS dereplication analysis of the active extracts showed the occurrence of several known anticancer compounds. Individual compounds, identified using HR-MS combined with analysis of the AntiMarin database, included saliniketals A and B, piericidins A and C and glucopiericidin A, staurosporine, N-methylstaurosporine, hydroxydimethyl-staurosporine and N-carbamoylstaurosporine, salinisporamycin A, and rifamycins S and B. BRA-199, identified as Streptomyces sp., was submitted to bioassay-guided fractionation, leading to isolation of the bioactive piericidins A and C, glucopiericidin, and three known diketopiperazines, cyclo(l-Phe-trans-4-OH-l-Pro), cyclo(l-Phe-l-Pro), and cyclo(l-Trp-l-Pro).

Keywords: Cytotoxic activities; Diketopiperazine; Marine microorganisms; Marine natural products; Piericidin.

MeSH terms

  • Actinobacteria / chemistry*
  • Actinobacteria / isolation & purification*
  • Antineoplastic Agents, Phytogenic / analysis*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Brazil
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Geologic Sediments / microbiology*
  • HCT116 Cells
  • Humans
  • Molecular Conformation
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic