Comparative study of stirred and fluidized tank reactor for hydroxyl-kojic acid derivatives synthesis and their biological activities

Abstract

Background:Study on the synthesis of kojic acid derivatives (KADs) in solvent-free system using scalable reactors and their biological activities is still lacking.Methods:In this study, two types of KADs, were synthesized using saturated-fatty acid [lauric acid (LA)] and unsaturated-fatty acid [oleic acid (OA)] in stirred tank reactor (STR) and fluidized tank reactor (FTR). The yield and biological activities of the synthesized KADs were evaluated and compared.Results:The highest yield of KADs (42.95%) was obtained in the synthesis using OA, with molar ratio of 1:1, enzyme loading of 5% (w/v), temperature of 70°C, using immobilized lipase N435 in STR. However, FTR may provide biocatalyst protection and reusability with reduced loss of KADs yield up to three cycles. In antioxidant assay, the hydroxyl-unsaturated-fatty acid of kojic acid (HUFA-KA) showed better activity as compared to hydroxyl-saturated-fatty acid of kojic acid (HSFA-KA) at concentrations ranging from 125 to 2000 μg/mL. In contrast, HSFA-KA showed better cytotoxicity effect against G361 melanoma cell as compared to HUFA-KA.Conclusion:The yield of KADs obtained in STR was higher than that obtained in FTR. HUFA-KA could be used as potential lipophilic antioxidant while HSFA-KA has the potential to be used to treat melanoma skin disorder.

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…Mechanism of action for depigmenting activity of one compound can also be varied depending on their molecular structure, size, chemical‐physical property, and even lipophilicity. For instance, hydrophilic KA (log P: −2) has low penetrative ability as compared KA esters (log P: 4) and KA derivatives of N‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (HTCC)—coated liposome . KA‐HTCC‐coated liposome derivatives have high penetrability, which has ability to reduce melanin content in B16 cell line to about 40% relative to untreated control, significantly better than uncoated KA …”

“…In general, cell culture—based evaluation may be grouped in six categories as shown in Figure . The specific examples include HEM, HEE, aneuploid immortal HaCaT, melan‐a, mel‐ab, P‐MDCK, SK‐MEL‐2, SH‐SY5Y, PC12, coculture, SP1/melan‐a, A375, G361, HMVII, MM418c5, MM418c1, HM3KO, Cloudman S19, RPMI‐1846, RPMI‐3460, MNT1 as well as B16 variants . The majority of melanoma cell lines are able to produce melanin such as A376, G‐361, HM3KO, A2058, and other cell lines.…”

“…Melanoma cell lines were normally grown in medium such as McCoy’s 5A, Dulbecco’s modified Eagle’s medium (DMEM), Ham’s F12/DMEM, Ham’s F12, DMEM, MEM, or RPMI‐1640 . In particular, DMEM with high glucose content is more preferable for growth of B16 cell lines and melanin synthesis than other media .…”

“…The specific examples include HEM, HEE, aneuploid immortal HaCaT, melan-a, mel-ab, P-MDCK, SK-MEL-2, SH-SY5Y, PC12, coculture, SP1/melan-a, A375, G361, HMVII, MM418c5, MM418c1, HM3KO, Cloudman S19, RPMI-1846, RPMI-3460, MNT1 as well as B16 variants. [105][106][107][108][109][110][111][112][113][114] The majority of melanoma cell lines are able to produce melanin such as A376, G-361, HM3KO, A2058, and other cell lines. In fact, melanin and its ratio (ie, eumelanin:pheomelanin) in melanoma are to some extent related to their survival, proliferation, and carcinogenesis.…”

“…McCoy's 5A, Dulbecco's modified Eagle's medium (DMEM), Ham's F12/DMEM, Ham's F12, DMEM, MEM, or RPMI-1640. 70,74,109,111,118 In particular, DMEM with high glucose content is more preferable for growth of B16 cell lines and melanin synthesis than other media. 7 High glucose media may provide sufficient energy in a form of ATP to support fast cell proliferation of melanoma cell line.…”