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.
Amjad Ayad Qatran Al-Khdhairawi  1 ,  Premanand Krishnan  1 ,  Chun-Wai Mai  2 ,  Felicia Fei-Lei Chung  3 ,  Chee-Onn Leong  2  3 ,  Kien-Thai Yong  4 ,  Kam-Weng Chong  5 ,  Yun-Yee Low  5 ,  Toh-Seok Kam  5 ,  Kuan-Hon Lim  1
Affiliations
  • 1. School of Pharmacy, University of Nottingham Malaysia Campus , Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
  • 2. School of Pharmacy, International Medical University , Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
  • 3. Center for Cancer and Stem Cell Research, International Medical University , Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
  • 4. Institute of Biological Sciences, Faculty of Science, University of Malaya , 50603 Kuala Lumpur, Malaysia.
  • 5. Department of Chemistry, Faculty of Science, University of Malaya , 50603 Kuala Lumpur, Malaysia.
PMID: 28926237 DOI: 10.1021/acs.jnatprod.7b00500
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).