Cladosporone A, a new dimeric tetralone from fungus Cladosporium sp. KcFL6’ derived of mangrove plant Kandelia candel

The mangroves habitats in tropical regions represent the terrestrial fringe of the marine habitats. Mangrove forests represent an ecosystem of high biodiversity. Their unique living conditions are thought to predestine mangroves as promising sources for isolation of endophytic fungi. Mangrove plants and their endophytic fungi have been a rich source of bioactive molecules.^1,2 More than 200 species of endophytic fungi were isolated and identified from various species of mangrove plants and have been proven to be a well-established source for structurally diverse and biologically active second metabolites.³ The genus Cladosporium was reported as a kind of main endophytic fungus of mangrove plant, which can produce remarkable diversity of secondary metabolites such as alkaloids,⁴ lactones,^5,6 diterpenoids⁷ and quinones.⁸ Cladosporol (=cladosporol A) was isolated from cultures of Cladosporium cladosporioides, which is plant growth regulator and antifungal agent in agriculture.⁹ Cladosporol inhibits colon cancer cell proliferation by modulating p21waf1/cip1 expression.¹⁰ PPARγ mediates the antiproliferative action of cladosporol in colorectal cancer cells.¹¹ In vivo, cladosporol also shows antitumor activity in nude mice bearing MGC-803 gastric-cancer xenografts.¹² Alterfungin is a chiral isomers of cladosporol which has strong broad-spectrum antifungal activity.¹³ Cladosporols B-E¹⁴ were isolated from C. tenuissinnum, a known hyperparasite of several rust fungi.¹⁵ These compounds were active in inhibiting the urediniospore germination of the bean rust agent Uromyces appendicalatus.

In our previous research toward the discovery of biologically active metabolites from endophytic fungus of Chinese mangrove plants, we obtained many active compounds.^{16, 17, 18} In our ongoing research, a new dimeric tetralone bridged through C–C linkage, was isolated, along with cladosporol (2), cladosporols C (3) and D (4). Herein, the isolation, structure elucidation and biological activities of metabolites 1–4 were presented.

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