title: Enzyme mediated-transesterification of verbascoside and evaluation of antifungal activity of synthesised compounds.
abstract: Enzymatic acylation of verbascoside, a polyhydroxylated natural product, has been reported in this study using five different commercial lipases and taking p-nitrophenyl alkanoates as acyl donors. Out of these enzymes, the immobilised Candida antarctica lipase B was found as the enzyme of choice. Mono- and di-acylated products were formed, with mono as major product indicating high regioselective nature of such transformations. A series of acyl esters of verbascoside have been synthesised by this enzymatic transesterification methodology. The lipophilicity of the synthesised analogues was also checked. The analogues were further subjected to synergistic antifungal activity with amphotericin B (AmB) against Candida albicans. Fourfold reduction in minimum inhibitory concentration of AmB was observed with few synthesised analogues such as verbascoside 4″-octanoate (3b), verbascoside 4″-palmitate (3d) and verbascoside 4″,4'-dipalmitate (4d) at a concentration of 0.5 μg/mL.
authors.affiliation: a Medicinal Chemistry Division, Indian Institute of Integrative Medicine (IIIM) , Canal Road, Jammu Tawi 180001 , India.
authors.forename: Jabeena
authors.initials: J
authors.lastname: Khazir
authors.forename: Intizar
authors.initials: I
authors.lastname: Ali
authors.forename: Inshad Ali
authors.initials: IA
authors.lastname: Khan
authors.forename: Halmuthur Mahabalarao Sampath
authors.initials: HM
authors.lastname: Kumar
mesh_terms: D000215:Acylation; D000935:Antifungal Agents / Q000737:chemistry*; D002175:Candida / Q000201:enzymology; D002176:Candida albicans / Q000187:drug effects*; D004357:Drug Synergism; D004951:Esterification; D005656:Fungal Proteins / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D059808:Polyphenols
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D005960:Glucosides; D008049:Lipase; D010636:Phenols; C058956:acteoside; D059808:Polyphenols; C431349:lipase B, Candida antarctica
keywords: acylation; antifungal activity; lipophilicity; transesterification; verbascoside