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  3. Synthesis of sorbicillinoid analogues with anti-inflammation activities

Synthesis of sorbicillinoid analogues with anti-inflammation activities

  • Bioorg Med Chem. 2022 Jan 15;54:116589. doi: 10.1016/j.bmc.2021.116589.
Meng Zhang 1,  Fangfang Wang 1,  Wenjuan Ding 1,  Zhipeng Xu 2,  Xiaosan Li 3,  Danmei Tian 1,  Youwei Zhang 4,  Jinshan Tang 5
Affiliations

Affiliations

  • 1 Institute of Traditional Chinese Medicine and Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • 2 Institute of Traditional Chinese Medicine and Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China; School of Pharmacy, Guangdong Medical University, Dongguan 523808, China.
  • 3 School of Pharmacy, Guangdong Medical University, Dongguan 523808, China.
  • 4 Department of Pharmacology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address: [email protected].
  • 5 Institute of Traditional Chinese Medicine and Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
PMID: 34971877 DOI: 10.1016/j.bmc.2021.116589
Abstract

Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage. Further chemical derivatization shows that the monomethylresorcinol skeleton worked better than the dimethylresorcinol skeleton in inhibiting LPS-induced inflammatory response in cultured cells. Among the 29 synthesized sorbicillinoid analogues, compounds 4b and 12b exhibited the strongest anti-inflammatory activities, holding the promise of being developed into lead compounds that can be explored as potent anti-inflammation agents.

Keywords

Anti-inflammatory effects; LPS; NO production; Sorbicillinoids; Structural modification; iNOS.

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