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.

摘要

从通过 ITS 区域 DNA 测序鉴定的Aspergillus N830 分离株的真菌培养物中分离出一种具有新的 6/6/6/5/6 环系统结构的新贝壳杉烯衍生物，简称为 caspicaiene 。该化合物通过 1、2 D NMR 和 HR-ESI-MS-MS 进行表征，并使用 Alamar Blue Assay (MABA) 以剂量依赖性方式显示出有希望的抗结核作用，MIC 值为 124.5 µM。此外，分离出六种已知化合物，并显示出对结核分枝杆菌的显着 MIC 值, 范围在 15.63 µg/mL (26.5 µM) 到 125 µg/mL (500 µM) 之间，与 MIC 值为 0.24 µg/mL (1.75 µM) 的阳性对照异烟肼相比，这表明它们是潜在的天然抗结核药代理。为了进一步了解潜在机制，使用 C-Docker 协议进行了硅内分子对接，并证明了分离的化合物与三种关键分枝杆菌酶之间的各种相互作用。此外，根据在人肝癌细胞系 (HepG2) 和 Vero 细胞系中计算的安全指数，报告了细胞毒活性并显示了这些分子的安全性。