Lovastatin Analogues from the Soil-Derived Fungus Aspergillus sclerotiorum PSU-RSPG178

  • J Nat Prod. 2016 Jun 24;79(6):1500-7. doi: 10.1021/acs.jnatprod.5b00961.
Patima Phainuphong ,  Vatcharin Rukachaisirikul ,  Saowanit Saithong ,  Souwalak Phongpaichit ,  Kawitsara Bowornwiriyapan ,  Chatchai Muanprasat  1 ,  Chutima Srimaroeng  2 ,  Acharaporn Duangjai  3 ,  Jariya Sakayaroj  4
Affiliations
  • 1. Department of Physiology, Faculty of Science, Mahidol University , Rajathevi, Bangkok 10400, Thailand.
  • 2. Department of Physiology, Faculty of Medicine, Chiang Mai University , Muang, Chiang Mai 50200, Thailand.
  • 3. Division of Physiology, School of Medical Sciences, University of Phayao , Muang, Phayao 56000, Thailand.
  • 4. National Center for Genetic Engineering and Biotechnology (BIOTEC) , Thailand Science Park, Klong Luang, Pathumthani 12120, Thailand.
PMID: 27228159 DOI: 10.1021/acs.jnatprod.5b00961
Abstract

Three new lovastatin analogues (1, 4, and 5) together with four known lovastatin derivatives, namely, lovastatin (2), α,β-dehydrolovastatin (3), α,β-dehydrodihydromonacolin K (6), and α,β-dehydro-4a,5-dihydromonacolin L (7), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound 5 exhibited the most potent activity against HMG-CoA reductase, with an IC50 value of 387 μM. In addition, the present study indicated the direct interaction of compound 5 with HMG-CoA reductase. Compound 5 was considered to be noncytotoxic against noncancerous Vero cells, with an IC50 value of 40.0 μM, whereas compound 2 displayed much stronger activity, with an IC50 value of 2.2 μM.