멜라닌 생합성 억제제로서 수용성 Oleanolic Acid 유도체의 합성 및 활성 평가

안현진; 윤영경; 이재덕; 정노희; Hyun-Jin An; Young-kyung Yoon; Jae-Duck Lee; Noh-Hee Jeong

Applied Chemistry for Engineering, Vol.31, No.6, 653-659, December, 2020

DOI10.14478/ace.2020.1078 Export Citation

멜라닌 생합성 억제제로서 수용성 Oleanolic Acid 유도체의 합성 및 활성 평가

Synthesis and Biological Evaluation of Water-Soluble Oleanolic Acid Derivatives for use as Melanogenesis Inhibitors

안현진^{1, 2}, 윤영경², 이재덕², 정노희^{1, †}

¹충북대학교 공업화학과
²여명바이오켐(주)

Hyun-Jin An^{1, 2}, Young-kyung Yoon³, Jae-Duck Lee³, and Noh-Hee Jeong^{1, †}

¹Department of Engineering Chemistry, Chungbuk National University, Cheongju 28644, Korea
²Yeomyung Biochem Co., Ltd., Cheongju 28171, Korea
³Yeomyung Biochem Co., Ltd., Korea

E-mail:

초록

본 연구에서는 메톡시폴리에틸렌글리콜(methoxy polyethylene glycol)과 올레아놀산(Oleanolic acid) 유도체(mPEG-OA derivative)를 합성하였으며, 합성된 유도체에 대하여 수용액에서의 용해도와 멜라닌 생성억제 효과를 평가하였다. mPEG-OA 유도체의 합성된 구조는 1H NMR, 13C NMR 및 FT-IR로 확인하였다. 수용액에서 mPEG-OA 유도체와 OA의 용해도를 측정한 결과, mPEG-OA 유도체는 13 mg/mL, OA는 0.013 mg/mL로서, mPEG-OA 유도체의 수용성이 OA보다 1,000배 높게 나타냈다. 세포생존율은 B16F10 melanoma cells에서, mPEG-OA 유도체의 세포생존율(250 μM)이 OA로 처리한 세포생존율(62.5 μM)과 비교하여 4배 증가하였다. 멜라닌 생합성 억제 효과는 세포생존율이 영향을 받지 않는 농도에서 측정하였으며, mPEG-OA 유도체는 50 μM의 농도에서 36%, OA는 10 μM의 농도에서 35%의 억제 효과를 나타내었다. B16F10 melanoma cells에서 MITF (microphthalmia-associated transcription factor)의 발현 억제 수준은 mPEG-OA 유도체는 50 μM의 농도에서 59%, OA는 10 uM의 농도에서 49%의 억제 효과를 나타내었다. 종합적으로 mPEG-OA 유도체와 OA의 수용성 및 미백활성을 비교한 결과, mPEG-OA 유도체는 OA보다 뛰어난 수용성을 가지며, 멜라닌 생합성을 억제하는 효과를 나타냄으로써 미백 기능성 화장품 소재로서 응용 가능성이 있음을 시사한다.

This study was focused on the synthesis of methoxy polyethylene glycol-oleanolic acid ester (mPEG-OA derivative) and investigation of its water solubility and anti-melanogenic effects. mPEG-OA derivative was identified by 1H and 13C NMR and FT-IR spectroscopic measurements. The water solubilities of mPEG-OA derivative and OA were found to be 13 and 0.013 mg/mL and that of mPEG-OA was found to be 1000-fold higher than that of OA. The effects of mPEG-OA derivative and OA on cell viability were measured using B16F10 melanoma cells. The viability of cells treated with mPEG-OA derivative (250 μM) increased 4-fold compared to that of cells treated with OA (62.5 μM). At mPEG-OA derivative and OA concentrations where the cell viability was unaffected, the inhibitory effect of mPEG-OA derivative and OA on the melanogenesis in B16F10 melanoma cells were 36 and 35% at 50 and 10 μM, respectively. The expression level of microphthalmia-associated transcription (MITF) was also reduced in B16F10 melanoma cells treated with mPEG-OA and OA. Overall, mPEG-OA derivative showed excellent water solubility and inhibitory effects of the melanogenesis, which could be used as a potential formulation for use in whitening functional cosmetic material.

Keywords:Oleanolic acid;Water solubility;Pegylation;Melanogenesis;Cosmetics material

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[6] Park SY, Jin ML, Kim YH, Kim Y, Lee SJ, Arch. Dermatol. Res., 303, 737 (2011)

[7] Tian T, Liu X, Lee ES, Sun J, Feng Z, Zhao L, Zhao C, Arch. Pharm. Res., 40, 458 (2017)

[8] Liu J, J. Ethnopharmacol., 100, 92 (2005)

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