title: Anomeric selectivity and influenza A virus inhibition study on methoxylated analogues of Pentagalloylglucose.
abstract: Anomeric selectivity in galloylation of D-glucose and D-mannose with carboxylic acid was explored under steglich conditions. Base catalyst 4-dimethylaminopyridine favored the formation of alpha-anomers, while adding an acid and carbodiimide favored the formation of beta-anomers. Steric hindrance between α,β-unsaturated acid and C-2 OH stereochemistry (adjacent carbon to anomeric) influenced anomeric selectivity for both D-glucose and D-mannose. The influenza A virus inhibition activities of the synthesized compounds were evaluated in Madin-Darby canine kidney cell line using the cytopathic effect inhibition assay. All the synthetic methoxylated analogues showed more considerable activity against influenza A virus than their corresponding acids, which indicated the sugar core as key functionality for anti-viral activity. The activities of trimethoxy-cinnamic acid Pentagalloylglucose analogues, 3α, 3β, 4α, and 4β (IC50, 109.1 μM, 134.4 μM, 119.5 μM, 111.1 μM, respectively) were better than those of trimethoxy-benzoic acid Pentagalloylglucose analogues, 1-αβ and 2α, 2β (IC50, 209.8 μM, 132.9 μM, 161.2 μM, respectively), which suggested that the double bond in cinnamic acid Pentagalloylglucose analogues makes the major contribution for influenza A virus inhibitory activity. Notably, several anomeric mixtures showed better activities than pure alpha or beta anomer and were almost two times more effective than Ribavirin, a clinically used anti-viral drug.
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Shaikh
authors.initials: S
authors.lastname: Qurat-ul-ain
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Meiting
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Na
authors.initials: N
authors.lastname: Du
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Shengbiao
authors.initials: S
authors.lastname: Wan
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. Electronic address: jiangtao@ouc.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004285:Dogs; D004951:Esterification; D004952:Esters; D047348:Hydrolyzable Tannins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004952:Esters; D047348:Hydrolyzable Tannins; C435084:pentagalloylglucose
keywords: Anomeric selectivity; Galloylation; Influenza A virus inhibition; Steglich esterification