Three new coumarins from Saposhnikovia divaricata and their porcine epidemic diarrhea virus (PEDV) inhibitory activity

Abstract

a b s t r a c tSwine based agro-industries throughout the world are in big threat of new PEDV infection due to lack of efficient prophylactic defenses as well as dependable curing agents. Bioactivity-guided fractionation of a methanol soluble extract from radix of Saposhnikovia divaricata led to the isolation of three new (1e3) together with 10 known coumarins (4e13). The structures of new isolates (1e3) were established by extensive spectroscopic analysis and their absolute configurations were assigned based on ECD spectra calculation and analysis. Among all isolates, compound 5 revealed strongest inhibitory effect on PEDV replication. Quantitative real-time PCR data showed inhibitory effect of 5 on genes responsible for synthesis of PEDV vital structural proteins (GP6 nucleocapsid, GP2 spike, and GP5 membrane) in a dosedependent manner. Also, compound 5 demonstrated the inhibitory effect on PEDV GP6 nucleocapsid and GP2 spike protein synthesis as analyzed by western blotting. This study represents a new class of chemical entities for developing anti-PEDV agents.

Saposhnikoviae divaricata : a phytochemical, pharmacological, and pharmacokinetic review

“…As a result, 4 SD phytochemical studies only [4][5][6][7] adhered to the scientific rigors that ensure the integrity in validation and robustness in quantitative outcomes. Among 9 phytochemistry papers with in vitro studies [8][9][10][11][12][13][14][15][16] , 5 [11,[13][14][15][16] were selected based on their relevance, but the phytochemistry component did not adhere to the selection criteria. A total of 10 in vitro studies only were included in this review [17][18][19][20][21][22][23][24][25][26] .…”

“…Structurally, natural products with phenolic groups with at least two polar groups in benzene ring at positions 6, 7 or 7, 8 are postulated to possess apoptotic properties while presence of hydroxyl groups at positions 5, 6, 7, and 8 of aromatic nucleus exhibit anti-inflammatory properties of hydroxycoumarins [40] . As part of the umbelliferae family, SD contains many natural coumarins and some of the SD pyranocoumarins substitution pattern indicated for praeruptorin F, cis-3'-isovaleryl-4'-acetylkhellactone, praeruptorin B, cis-3', 4'-disenecioylkhellactone, cis-3'-isovaleryl-4'-senecioylkhellactone, (−)-cis-khellactone were at C-8/C-1'/C-3'/0/C-7, with divaricoumarins at C7 and C8 [10] . Moreover, strong synergistic interactions were also featured when pyranocoumarins were combined with common anti-tumor drugs such as vincristine, doxorubicin, and PTX [41] .…”

“…The crude dried roots of SD contain chromones and coumarins, which are both heterocyclic compounds, derived from the flavonoids. Chromone is a class of oxygen-containing heterocyclic compound with a benzo annelated γ-pyrone ring, belonging to a subclass of the flavonoids known as flavone [10] ; while coumarin, a benzopyrone, structurally consists of a benzene ring fused to a pyrone ring. A total of 9 chromones are identified in the included studies.…”

“…New discoveries of coumarins in SD have also emerged over recent years. Three new coumarin compounds are discovered to have effects against porcine epidemic diarrhea virus (PEDV): divaricoumarin A, divaricoumarin B, and divaricoumarin, with molecular formulae being C 25 [10] (Fig. 2).…”

“…In vitro results reveal Praeruptorin B is able to inhibit viral replication at the stage of protein syntheses. Although PEDV is essentially a viral infection in pigs, this coronavirus stems from the same family of the human coronaviruses, such as severe acute respiratory syndrome and Middle East respiratory syndrome [10] . Praeruptorin B, a coumarin from SD, could potentially offer a novel anti-viral drug research for the intractable human coronavirus diseases.…”