Caspicaiene: a new kaurene diterpene with anti-tubercular activity from an Aspergillus endophytic isolate in Gleditsia caspia desf

Abstract

A new kaurene derivative with a new 6/6/6/5/6 ring system structure, given the trivial name caspicaiene, was isolated from the fungal culture of the Aspergillus N830 isolate identified by ITS region DNA sequencing. The compound was characterized by 1, 2 D NMR, and HR-ESI-MS-MS and revealed a promising anti-tubercular effect using the Alamar Blue Assay (MABA), in a dose dependent manner, with MIC value of 124.5 µM. Furthermore, six known compounds were isolated and showed significant MIC values against Mycobacterium tuberculosis, ranging between 15.63 µg/mL (26.5 µM) to 125 µg/mL (500 µM), compared to the positive control isoniazid whose MIC value was 0.24 µg/mL (1.75 µM), which sets them forth as potentially natural anti-tubercular agents. To gain further insight of the underlying mechanism, in-silico molecular docking, using the C-Docker protocol, was conducted and demonstrated various interactions between the isolated compounds and three key mycobacterial enzymes. Additionally, the cytotoxic activity was reported and showed the safety of these molecules according to the calculated safety index in the human hepatic cancer cell line (HepG2) and Vero cell lines.

Graphical Abstract

Keywords:

• Anti-tuberculosis
• endophytes
• caspicaiene
• molecular docking
• kaurene diterpenes

Acknowledgement

The authors are thankful to the STDF for providing the NMR facility and the UPLC ESIMS in the Center for Drug Discovery and Research Development.

Disclosure statement

The authors declare no conflict of interest.

Author contributions

A.Y.M. has done the structure elucidation of the compounds, writing and editing the manuscript, H.A.S. conducted the experimental part and collecting data, O.A.E. revised and supervised the manuscript, A.B.S. revised and supervised the manuscript.