Asperidines A–C, pyrrolidine and piperidine derivatives from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178. Issue 15 (15th August 2018)

• Record Type: Journal Article
• Authors: Phainuphong, Patima; Rukachaisirikul, Vatcharin; Saithong, Saowanit; Phongpaichit, Souwalak; Sakayaroj, Jariya; Srimaroeng, Chutima; Ontawong, Atcharaporn; Duangjai, Acharaporn; Muangnil, Paradorn; Muanprasat, Chatchai
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 15(2018)
• Page Start: 4502
• Page End: 4508
• Publication Date: 2018-08-15
• Subjects: Aspergillus sclerotiorum -- Pyrrolidine derivative -- Piperidine derivative -- CFTR inhibitor -- Antioxidant -- Cytotoxicity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.07.036
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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. Compound3 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 compounds2 and3 were established using Mosher's method and further confirmed for compound3 by X-ray crystallographic data. Compound2 dose-dependently inhibited the CFTR-mediated chloride secretion in T84 cells with an IC50 value of 0.96 μM whereas3 displayed the same activity with the IC50 value of 58.62 μM. Compounds2 and3 also significantly reduced intracellular ROS under both normal and H2 O2 -treated conditions compared with their respective controls in a dose-dependent manner without cytotoxic effect on Caco-2 cells. In addition, compound3 was inactive against noncancerous Vero cells whereas compound2 was considered to be inactive with the IC50 value of >10 μM.