Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Depsidones and a dihydroxanthenone from the endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261 Vatcharin Rukachaisirikul a,⁎ , Supaporn Chinpha a , Praphatsorn Saetang a , Souwalak Phongpaichit b , Siriporn Jungsuttiwong c , Sarinya Hadsadee c , Jariya Sakayaroj d , Sita Preedanon e , Prapapan Temkitthawon f , Kornkanok Ingkaninan f a Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand b Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand c Department of Chemistry, Faculty of Science, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand d School of Science, Walailak University, Thasala, Nakhonsithammarat 80161, Thailand e National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park, Klong Luang, Pathumthani 12120, Thailand f Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand ARTICLEINFO Keywords: Simplicillium lanosoniveum Depsidones Dihydroxanthenone Antimicrobial activity PDE5 inhibition ABSTRACT Three new compounds including two depsidones (simplicildones J and K) and one dihydroxanthenone (globo- suxanthone E) together with nine known compounds were obtained from the crude extracts of two endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261 which were isolated from the leaves of Hevea brasiliensis. The structures were elucidated by spectroscopic evidence. The absolute confguration of globosuxanthone E was established by means of experimental and calculated TDDFT ECD data. Simplicildone K exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 128 μg/mL. Simplicildone K and globosuxanthone E displayed antifungal activity against Cryptococcus neoformans ATCC90113 with the same MIC values of 32 μg/mL. In addition, known bo- tryohordine C and simplicildone A showed phosphodiesterase 5 inhibitory activity with the IC 50 values of 5.69 and 9.96 μM, respectively, and were noncytotoxic toward noncancerous Vero cells. 1. Introduction Simplicillium used to be a group of species in the sect. Prostrata of Verticilium and belongs to the Cordycipitaceae, Hypocreales. The spe- cies S. lanosoniveum (J.F.H. Beyma) Zare & W. Gams is actually the type species of the genus [1]. The genus Simplicillium has been recognized as an important source of bioactive secondary metabolites including an- tibacterial halymecin F [2] and botryorhodine C [3], antifungal sim- plifungin [4] and sinulariapeptide A [5], anticancer simplicilliumtides GandH[6] and antiviral verlamelins A and B [7]. In an efort to search for bioactive compounds from fungi, we studied two fungal endophytes, which were isolated from the leaves of Hevea brasiliensis and identifed as Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261. To the best of our knowledge, only two reports of secondary metabolites of S. lanosoniveum (J.F.H. Beyma) Zare & W. Gams have been published [8,9]. The broth extract of the fungus PSU- H261 exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with the respective MIC values of 16 and 32μg/mL and showed interesting phosphodiesterase 5 (PDE5) in- hibitory activity with 99.5% at the concentration of 50 μg/mL. In contrast, the broth extract of the other fungus PSU-H168 showed no antibacterial and PDE5 inhibitory activities at the concentration of 200 and 50 μg/mL, respectively. Chemical investigation of the crude ex- tracts of both fungi resulted in the isolation of three new compounds including two depsidones, simplicildones J and K (1 and 2) and one dihydroxanthenone derivative, globosuxanthone E (3), together with nine known compounds, (−)-nigrosporione A (4)[10], (S)-dihydro-5- [(S)-hydroxyphenylmethyl]-2(3H)-furanone (5)[11], 4-oxo-5-phe- nylpentanoic acid (6)[12], isoevernin aldehyde (7)[13], penicillic acid (8)[14], botryorhodines B and C (9 and 10)[15], and simplicildones A https://doi.org/10.1016/j.ftote.2019.104286 Received 1 June 2019; Received in revised form 31 July 2019; Accepted 2 August 2019 ⁎ Corresponding author. E-mail address: vatcharin.r@psu.ac.th (V. Rukachaisirikul). Fitoterapia 138 (2019) 104286 Available online 05 August 2019 0367-326X/ © 2019 Elsevier B.V. All rights reserved. T