(R)-Fangchinoline

Fangchinoline, a bisbenzylisoquinoline alkaloid, is a novel HIV-1 inhibitor with pain-relieving, blood pressure-depressing, and antibiotic activities.

Fangchinoline (FCL) exhibits antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 ?M. The compound targets a late event in infection cycle. Fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing[1]. FCL inhibits autophagosomes-lysosomes fusion, decreases the activities of cathepsin B and cathepsin D and affects the cellular acidification. FCL also increases the nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes, and the mRNA expressions of TFEB-targeted genes, such as SQSTM1, MAP1LC3B, and UVRAG. Knockdown of TFEB by using small inference RNA decreases the FCL-induced expression of LC3-II and the formation of GFP-LC3 puncta[2]. Fangchinoline effectively suppresses proliferation and invasion of SGC7901 cell lines, but not MKN45 cell lines by inhibiting the expression of PI3K and its downstream pathway. fangchinoline targets PI3K in tumor cells that express PI3K abundantly and inhibits the growth and invasive ability of the tumor cells[3]. Fangchinoline is also a non-specific calcium antagonist[4].

Fangchinoline attenuates morphine (SC)-induced antinociception in a dose-dependent manner with significant effect at doses of 30 and 60mg/kg body wt. (IP) in the tail-flick test but not the tail-pinch tests, carried out in mice[4].

[1] Wan Z, et al. PLoS One. 2012, 7(6):e39225. [2] Zheng-Hai Tang, et al. RSC Adv. 2017,7:42597-42605. [3] Tian F, et al. Int J Oncol. 2015, 46(6):2355-63.