Asperidines A-C, pyrrolidine and piperidine derivatives from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178

  • Bioorg Med Chem. 2018 Aug 15;26(15):4502-4508. doi: 10.1016/j.bmc.2018.07.036.
Patima Phainuphong  1 ,  Vatcharin Rukachaisirikul  2 ,  Saowanit Saithong  1 ,  Souwalak Phongpaichit  3 ,  Jariya Sakayaroj  4 ,  Chutima Srimaroeng  5 ,  Atcharaporn Ontawong  6 ,  Acharaporn Duangjai  7 ,  Paradorn Muangnil  8 ,  Chatchai Muanprasat  8
Affiliations
  • 1. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
  • 2. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. Electronic address: [email protected].
  • 3. Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
  • 4. School of Science, Walailak University, Tha Sala, Nakhon Si Thammarat 80161, Thailand.
  • 5. Department of Physiology, Faculty of Medicine, Chiang Mai University, Mueang District, Chiang Mai 50200, Thailand.
  • 6. Department of Physiology, Faculty of Medicine, Chiang Mai University, Mueang District, Chiang Mai 50200, Thailand; Division of Physiology, School of Medical Sciences, University of Phayao, Mueang District, Phayao 56000, Thailand.
  • 7. Division of Physiology, School of Medical Sciences, University of Phayao, Mueang District, Phayao 56000, Thailand.
  • 8. Excellent Center for Drug Discovery and Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
PMID: 30078607 DOI: 10.1016/j.bmc.2018.07.036
Abstract

One new pyrrolidine derivative, asperidine A (1), and two new piperidine derivatives, asperidines B (2) and C (3), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178 together with two known Alkaloids. Compound 3 possessed an unprecedented 7-oxa-1-azabicyclo[3.2.1]octane skeleton with four chiral centers. Their structures were determined by spectroscopic evidence. The absolute configurations of compounds 2 and 3 were established using Mosher's method and further confirmed for compound 3 by X-ray crystallographic data. Compound 2 dose-dependently inhibited the CFTR-mediated chloride secretion in T84 cells with an IC50 value of 0.96 μM whereas 3 displayed the same activity with the IC50 value of 58.62 μM. Compounds 2 and 3 also significantly reduced intracellular ROS under both normal and H2O2-treated conditions compared with their respective controls in a dose-dependent manner without cytotoxic effect on Caco-2 cells. In addition, compound 3 was inactive against noncancerous Vero cells whereas compound 2 was considered to be inactive with the IC50 value of >10 μM.

Keywords
Antioxidant; Aspergillus sclerotiorum; CFTR inhibitor; Cytotoxicity; Piperidine derivative; Pyrrolidine derivative.