Evaluation of Wound Healing Potential of (5-formylfuran-2-yl)Methyl Benzoates by In Vitro Cell Culture Studies

5-hydroxymethylfurfural (5-HMF) derivatives, found in many natural products, exhibit various biological activities. Benzoate derivatives enhance cellular re-epithelialization without inducing cytotoxicity. This study aimed to evaluate the wound-healing potential of six benzoate derivatives of 5-HMF by usingan in vitro cell culture method.

Six ester derivatives of 5-HMF were synthesized, and the molecular structures were elucidated by proton-1 nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and Quadrupole time-of-flight mass spectrometry. The effects of the compounds on neuronal and fibroblast cell survival were determined in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The total oxidation state (TOS) and total antioxidant capacity (TAC) were measured spectrophotometrically. The effects of the lead compounds (M3 and M5) on fibroblast migratory potential were evaluated using a wound-healing scratch assay.

The MTT test showed that M2, M3, M5, and M6 did not damage fibroblasts at any tested concentration (10^-1 μM-10^-2 μM). M3 and M5 increased fibroblast cell numbers at all tested concentrations (p≤0.05 to p≤0.001). It was observed that M2, M3, M5, and M6 at concentrations of 10^-1 μM and 1 μM did not damage the neuronal cells. Also, M3 and M5 did not damage neuronal cells at 10 μM. M3 and M5 exhibited lower oxidant activity (p≤0.001) than other compounds in TOS tests, and showed higher antioxidant activity than other compounds in TAC tests. In the scratch test, the wound area in the M3 group was 72% on the first day and decreased to 32% on the second day (p≤0.001). On the other hand, in the M5 group, the wound area was 81% on the first day and decreased to 25% on the second day (p≤0.001).

M3 and M5 promote cell migration and have the highest potential for wound healing among the compounds tested.