2. Academic Validation
  3. A dimeric urea of the bisabolene sesquiterpene from the Okinawan marine sponge Axinyssa sp. inhibits protein tyrosine phosphatase 1B activity in Huh-7 human hepatoma cells

A dimeric urea of the bisabolene sesquiterpene from the Okinawan marine sponge Axinyssa sp. inhibits protein tyrosine phosphatase 1B activity in Huh-7 human hepatoma cells

  • Bioorg Med Chem Lett. 2016 Jan 15;26(2):315-317. doi: 10.1016/j.bmcl.2015.12.022.
Delfly B Abdjul 1,  Syu-Ichi Kanno 1,  Hiroyuki Yamazaki 2,  Kazuyo Ukai 1,  Michio Namikoshi 1
Affiliations

Affiliations

  • 1 Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
  • 2 Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan. Electronic address: yamazaki@tohoku-pharm.ac.jp.
PMID: 26711144 DOI: 10.1016/j.bmcl.2015.12.022
Abstract

Protein tyrosine Phosphatase 1B (PTP1B) plays an important role as a negative regulator of the Insulin and Leptin signaling pathways. Therefore, this Enzyme is regarded as an attractive therapeutic target for the treatment of type 2 diabetes and obesity. Our screening program for PTP1B inhibitors led to the isolation of four Sesquiterpenes and sterol: N,N'-bis[(6R,7S)-7-amino-7,8-dihydro-α-bisabolen-7-yl]urea (1), (6R,7S)-7-amino-7,8-dihydro-α-bisabolene (2), (1R,6S,7S,10S)-10-isothiocyanato-4-amorphene (3), axinisothiocyanate J (4), and axinysterol (5) from the marine Sponge Axinyssa sp. collected at Iriomote Island. Of these, compound 1 was the most potent inhibitor of PTP1B activity (IC50=1.9μM) without cytotoxicity at 50μM in two human Cancer cell lines, hepatoma Huh-7 and bladder carcinoma EJ-1 cells. Compound 1 also moderately enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells. Therefore, compound 1 has potential as a new type of anti-diabetic drug candidate possessing PTP1B inhibitory activity.

Keywords

Axinyssa sp.; Bisabolene; Inhibitor; Marine sponge; Protein tyrosine phosphatase 1B.

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