Synthesis and Biological Characterization of the New Glycolipid Lactose Undecylenate (URB1418)

Abstract

As a follow-up to our previous studies on glycolipid surfactants, a new molecule, that is lactose 6′-O-undecylenate (URB1418), was investigated. To this end, a practical synthesis and studies aimed at exploring its specific properties were carried out. URB1418 showed antifungal activities against Trichophyton rubrum F2 and Candida albicans ATCC 10231 (MIC 512 μg/mL) and no significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. At the same time, it presented anti-inflammatory properties, as documented by the dose-dependent reduction in LPS-induced NO release in RAW 264.7 cells, while a low antioxidant capacity in the range of concentrations tested (EC50 > 200 µM) was also observed. Moreover, URB1418 offers the advantage of being more stable than the reference polyunsaturated lactose esters and of being synthesized using a “green” procedure, involving an enzymatic method, high yield and low manufacturing cost. For all these reasons and the absence of toxicity (HaCaT cells), the new glycolipid presented herein could be considered an interesting compound for applications in various fields.

Synthesis and Biological Evaluation of 6-O-Sucrose Monoester Glycolipids as Possible New Antifungal Agents

“…As indicated in Figure 1 , URB1537 did not show scavenger effects against DPPH radicals within the range of concentrations tested (EC 50 >> 512 µg/mL). This evidence agrees with previous findings showing that sugar esters possess lower radical scavenging properties than the reference antioxidant molecules [ 24 , 38 , 39 ], such as quercetin (calculated EC 50 equal to 1.74 µg/mL). In particular, sugar esters show scavenger abilities at concentrations ranging from 1 to 10 mg/mL, higher than those herein tested for URB1537 (up to 512 µg/mL).…”

“…Overall, these data agree with previous observations demonstrating that sucrose fatty acid esters exhibit anti-inflammatory effects through different mechanisms, such as the inhibition of NF-κB activation involved in immunity and inflammation [ 41 ]. Similarly, we have recently observed that some lactose-based fatty acid esters may counteract NO production in LPS-stimulated macrophages [ 24 ].…”

“…As part of our ongoing investigations on the synthesis, biological activities, and applications of sugar derivatives [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], a series of 6- O -sucrose monoesters were designed and synthesized by using an opportunely modified Mitsunobu-type methodology [ 25 ] starting from free sucrose and lipophilic acids. This coupling, compared to the others reported in the literature [ 8 , 10 ], such as esterification (acyl chlorides, anhydrides) and transesterification with activated esters (vinyl or enol esters) [ 26 , 27 , 28 , 29 ], and/or enzymatic preparation methods [ 30 , 31 , 32 ], showed higher conversions/yields, high regioselectivity and larger scope including saturated, mono- and polyunsaturated fatty acids or aromatic and alkyl aromatic acids.…”

Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers

“…Among all of them, sugar-based fatty acid esters are the most common and easy to find on the market due to their many investigated applications. In particular, the emulsifying and permeability-enhancing ability as well as the antimicrobial and antibiofilm properties of lactose-based esters with saturated and unsaturated fatty acid have been described previously by our group [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Moreover, we synthesized a series of lactose-based monoesters bearing saturated C10, C12, C14, or C16 acyl chains and evaluated cytotoxicity and the ability to decrease transepithelial electrical resistance (TEER) on airway epithelium Calu-3 cells.…”