Aspochalasin H1: A New Cyclic Aspochalasin from Hawaiian Plant-Associated Endophytic Fungus Aspergillus sp. FT1307.

Mallique Qader,Xiaohua Wu,Kh Ahammad Uz Zaman,Zhenquan Hu,Shugeng Cao,Cong Wang,K H Ahammad Uz Zaman

doi:10.3390/molecules26144239

Abstract

Aspergillus is one of the most diverse genera, and it is chemically profound and known to produce many biologically active secondary metabolites. In the present study, a new aspochalasin H1 (1), together with nine known compounds (2–10), were isolated from a Hawaiian plant-associated endophytic fungus Aspergillus sp. FT1307. The structures were elucidated using nuclear magnetic resonance (NMR) (1H, 1H-1H COSY, HSQC, HMBC, ROESY and 1D NOE), high-resolution electrospray ionization mass spectroscopy (HRESIMS), and comparisons with the reported literature. The absolute configuration of the new compound was established by electronic circular dichroism (ECD) in combination with NMR calculations. The new compound contains an epoxide moiety and an adjacent trans-diol, which has not been reported before in the aspochalasin family. The antibacterial screening of the isolated compounds was carried out against pathogenic bacteria (Staphylococcus aureus, Methicillin-resistant S. aureus and Bacillus subtilis). The antiproliferative activity of compounds 1–10 was evaluated against human breast cancer cell lines (MCF-7 and T46D) and ovarian cancer cell lines (A2780).

Highlights

Searching for antimicrobial agents has become one of the major research fields in natural products chemistry [1,2] because the development of pathogens resistant to the clinically used antimicrobials has been increasing alarmingly day by day [3,4]
Due to the obvious 13C chemical shift difference in the stereocenters (C-17, C-18, C-19 and C-20) of 1 from the nuclear magnetic resonance (NMR) data of aspochalasin H, we concluded that 1 was a stereoisomer of aspochalasin H, probably with a different diol orientation. 2D ROESY provided important information on the proton signals arising from each proton through the space, even though they were not bonded to each other
The ROESY experiment showed correlations between H-4 and H-8, between H-4 and H-10, and between H-3 and H-11, which were identical to the isoindolone moiety of the reported cytochalasans, especially aspochalasin H [26], except H-17, H-18, H-19 and H-20

Summary

Introduction

Searching for antimicrobial agents has become one of the major research fields in natural products chemistry [1,2] because the development of pathogens resistant to the clinically used antimicrobials has been increasing alarmingly day by day [3,4]. The usage of initially discovered antibiotics and antifungal drugs in treating human diseases has been greatly reduced [5]. There is an urgent need for new antibiotics in order to tackle, in particular, antimicrobial resistance. The diversity and the distribution of the fungi in a diverse array of habitats categorized them as an understudied group of organisms [7]. Fungi are considered remarkable and valuable organisms as they have provided the world with medicinally important drugs such as antibiotics, anticancer agents, cholesterol lowering statins, immunomodulators, and agriculturally important herbicides and weedicides, and they are environmentally important as decomposers and for the distribution of nutrients [8,9,10,11]

Methods

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Discussion

Conclusion