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.

Keywords::

• transesterification
• verbascoside
• acylation
• lipophilicity
• antifungal activity

Acknowledgements

The authors thank the Director, CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu for providing facilities to carry this work and for his constant support. Thanks are also due to Dr Parvinder Pal, Dr Qazi Naveed and Dr S.D. Sawant for their support. Special thanks to Dr Syed Shafi and Dr K.A Suri for providing the verbascoside. Thanks are also due to IIIM and University of Pretoria for providing Doctoral and Postdoctoral fellowships to JK.