title: Design, synthesis, and anti-tobacco mosaic virus (TMV) activity of glycoconjugates of phenanthroindolizidines alkaloids.
abstract: Glycoconjugates of phenanthroindolizidine alkaloids targeting tobacco mosaic virus (TMV) RNA were designed, synthesized, and evaluated for their antiviral activity against TMV for the first time. The glycoconjugation of (S)-6-O-desmethylantofine (2) and 14-hydroxyltylophorines (3-6) was accomplished in three ways (O-glycosylation manner, using carbamoyloxy as linker arm, and using 1,2,3-triazole as linker arm) with three different sugar units (glucose, galactose, and mannose). The glycoconjugates showed improved water solubility and molecule polarity compared with phenanthroindolizidine alkaloids. The bioassay results showed that C6 was a suitable position for glycoconjugation and O-glycosylation can increase the antiviral activity of phenanthroindolizidine alkaloids indicating that the introduction of sugar units can improve the antiviral activity profile of glycoconjugates. Two O-glycosides of (S)-6-O-desmethylantofine, (13aS)-6-O-β-D-galactopyranosyl-2,3-dimethoxyphenanthro [9,10-b]-11-indolizidinone (10) and (13aS)-6-O-β-D-mannopyranosyl-2,3-dimethoxyphenanthro [9,10-b]-11-indolizidinone (11) displayed significant higher activity than commercial ningnanmycin, and thus could be considered for novel therapy against plant virus infection.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.forename: Guifang
authors.initials: G
authors.lastname: Han
authors.forename: Chuisong
authors.initials: C
authors.lastname: Meng
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007212:Indolizines / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D006001:Glycoconjugates; D007212:Indolizines; D010618:Phenanthrolines; C521640:phenanthroindolizidine