Design, development and synthesis of mixed bioconjugates of piperic acid–glycine, curcumin–glycine/alanine and curcumin–glycine–piperic acid and their antibacterial and antifungal properties

Abstract

In the present communication different curcumin bioconjugates viz. 4,4′-di- O-glycinoyl-curcumin, 4,4′-di- O- d-alaninoyl-curcumin, 4,4′-di- O-(glycinoyl-di- N-piperoyl)-curcumin, 4,4′-di- O-piperoyl curcumin, curcumin-4,4′-di- O-β- d-glucopyranoside, 4,4′-di- O-acetyl-curcumin along with piperoyl glycine, have been synthesised and characterised by spectra UV, 1H NMR and elemental analysis. All the covalent bonds used are biodegradable. This makes these derivatives as potent prodrugs, which can get hydrolysed at the target sites. These bioconjugates were tested in vitro against different bacteria and fungi. The 4,4′-di- O-(glycinoyl-di- N-piperoyl)-curcumin and 4,4′-di- O-acetyl-curcumin are more effective than Cefepime, an antibacterial drug available in market, at the same concentration. The 4,4′-di- O-(glycinoyl-di- N-piperoyl)-curcumin and 4,4′-di- O-piperoyl curcumin had antifungal activity in vitro almost comparable with fluconazole, the most popular antifungal drug. The enhanced activity of these bioconjugates vis-à-vis the parent molecule that is curcumin may be due to improved cellular uptake or reduced metabolism of these bioconjugates resulting in building up of enough concentration inside the infected cells. It opens a new era for exploring suitably designed curcumin bioconjugates as potential antibacterial/antifungal drugs.