A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis

J Nat Prod. 2017 Oct 27;80(10):2734-2740. doi: 10.1021/acs.jnatprod.7b00500. Epub 2017 Sep 19.

Abstract

Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (+)-1 and (-)-1 were established via experimental and calculated ECD data. Compound 1 is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound 2 represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-1 displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC50 7.4 μM), while compound 2 showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC50 values of 0.038-0.91 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification*
  • Alkaloids / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy
  • Crystallography, X-Ray
  • Cyclobutanes / chemistry
  • Cyclobutanes / isolation & purification*
  • Cyclobutanes / pharmacology*
  • Ficus / chemistry*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / isolation & purification*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Indolizines / chemistry
  • Inhibitory Concentration 50
  • Isoquinolines
  • Malaysia
  • Molecular Conformation
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Phenanthrolines / chemistry
  • Plant Leaves / chemistry
  • Stereoisomerism

Substances

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Cyclobutanes
  • Heterocyclic Compounds, 4 or More Rings
  • Indolizines
  • Isoquinolines
  • Phenanthrolines
  • phenanthroindolizidine
  • tengechlorenine
  • tengerensine