Enhancing the Bioconversion of Azelaic Acid to Its Derivatives by Response Surface Methodology

Abstract

Azelaic acid (AzA) and its derivatives have been known to be effective in the treatment of acne and various cutaneous hyperpigmentary disorders. The esterification of azelaic acid with lauryl alcohol (LA) to produce dilaurylazelate using immobilized lipase B from Candida antarctica (Novozym 435) is reported. Response surface methodology was selected to optimize the reaction conditions. A well-fitting quadratic polynomial regression model for the acid conversion was established with regards to several parameters, including reaction time and temperature, enzyme amount, and substrate molar ratios. The regression equation obtained by the central composite design of RSM predicted that the optimal reaction conditions included a reaction time of 360 min, 0.14 g of enzyme, a reaction temperature of 46 °C, and a molar ratio of substrates of 1:4.1. The results from the model were in good agreement with the experimental data and were within the experimental range (R2 of 0.9732).The inhibition zone can be seen at dilaurylazelate ester with diameter 9.0±0.1 mm activities against Staphylococcus epidermidis S273. The normal fibroblasts cell line (3T3) was used to assess the cytotoxicity activity of AzA and AzA derivative, which is dilaurylazelate ester. The comparison of the IC50 (50% inhibition of cell viability) value for AzA and AzA derivative was demonstrated. The IC50 value for AzA was 85.28 μg/mL, whereas the IC50 value for AzA derivative was more than 100 μg/mL. The 3T3 cell was still able to survive without any sign of toxicity from the AzA derivative; thus, it was proven to be non-toxic in this MTT assay when compared with AzA.

Optimisation of Epoxide Ring-Opening Reaction for the Synthesis of Bio-Polyol from Palm Oil Derivative Using Response Surface Methodology

“…A positive sign in the equation showed a synergistic effect. A negative sign indicated as an antagonistic effect [ 33 , 34 ].…”

“…The important influence of efficient variables on the hydroxyl value was demonstrated by Pareto analysis as shown in Figure 7 . The Pareto analysis expresses the influence of each variable, in percentages, on the response in relation to the coefficient of the coded variable in Equation (3) [ 33 , 47 ]. The pareto analysis showed that variable B (catalyst) gave the most important influence on the response (hydroxyl value) at 45.89% followed by variable A (mole ratio of EMO:Glycerol) at 37.61% and the interaction between A and B at 6.98%.…”

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…268 Azelaic acid was diesterified with lauric alcohol using N435 and used as a bacteria growth inhibitor. 269 Another paper shows that methyl caffeate production via esterification catalyzed by N435 was improved via a microfluidic strategy in a continuous-flow reactor (yields surpassed 98% in 2.5 h). 270 N435 was also used in the esterification of oleic acid and kojic acid in a stirred tank reactor with a yield near 43%.…”

Lipase B from Candida antarctica — the wide applicable biocatalyst in obtaining pharmaceutical compounds

“…The derivates of the azelaic acid are characterized by better solubility and require less dosage than acid form. The synthesis by esterification of azelaic acid with lauryl alcohol, catalyzed by CAL-B (Novozym 435) was carried out by Khairudin et al The high conversion (> 95%) was achieved with a small amount of enzyme [19].…”