1. Academic Validation
  2. Aniline-Tetramic Acids from the Deep-Sea-Derived Fungus Cladosporium sphaerospermum L3P3 Cultured with the HDAC Inhibitor SAHA

Aniline-Tetramic Acids from the Deep-Sea-Derived Fungus Cladosporium sphaerospermum L3P3 Cultured with the HDAC Inhibitor SAHA

  • J Nat Prod. 2018 Jul 27;81(7):1651-1657. doi: 10.1021/acs.jnatprod.8b00289.
Zhenzhen Zhang 1 Xueqian He 1 Guangwei Wu 1 Congcong Liu 1 Changjun Lu 1 Qianqun Gu 1 Qian Che 1 Tianjiao Zhu 1 Guojian Zhang 1 2 Dehai Li 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy , Ocean University of China , Qingdao 266003 , People's Republic of China.
  • 2 Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology , Qingdao 266237 , People's Republic of China.
Abstract

Four new tetramic acids, cladosins H-K (1-4), and a related known compound, cladodionen (5), were isolated from the culture of the Mariana Trench (depth 6562 m) sediment-derived fungus Cladosporium sphaerospermum L3P3 treated with the histone deacetylase inhibitor SAHA (suberanilohydroxamic acid). Interestingly, compounds 1-5 existed as equilibrium E/ Z mixtures and 1-4 were the first cases of tetramic acids containing aniline moieties. Their structures including absolute configurations were elucidated through a combination of NMR, MS, and Mosher's method, together with the consideration of biogenetic origins. Incubation experiments of exogenous aniline and N-phenyloctanamide revealed that the aniline moiety in cladosins H-K (1-4) is probably derived from the degradation of SAHA, indicating that the well-known histone deacetylase inhibitor SAHA could be metabolized by L3P3 and provide aniline as a precursor for biotransformation of chemically reactive polyketides. The cytotoxicity of 1-5 was evaluated against the PC-3, MGC-803, SH-SY5Y, HCT-116, K562, and HL-60 cell lines, and compound 2 showed promising cytotoxicity against the HL-60 cell line with an IC50 value of 2.8 μM.

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