Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper methysticum and synthesis of analogs

  • Bioorg Med Chem Lett. 2015 Feb 15;25(4):799-802. doi: 10.1016/j.bmcl.2014.12.082.
Hye-Jin Jeong  1 ,  Chang Seok Lee  2 ,  Janggyoo Choi  3 ,  Yong Deog Hong  2 ,  Song Seok Shin  2 ,  Jun Seong Park  2 ,  John Hwan Lee  2 ,  Seokyong Lee  4 ,  Kee Dong Yoon  5 ,  Jaeyoung Ko  6
Affiliations
  • 1. Development Group for Global New Drug Developing Human Resources (BK21 Plus Project), Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwan, Gyeonggi-do 440-746, Republic of Korea.
  • 2. Amorepacific R&D Unit, 314-1 Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 449-729, Republic of Korea.
  • 3. College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, Republic of Korea.
  • 4. School of Pharmacy, Sungkyunkwan University, Suwan, Gyeonggi-do 440-746, Republic of Korea.
  • 5. College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon-si, Republic of Korea. Electronic address: [email protected].
  • 6. Amorepacific R&D Unit, 314-1 Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 449-729, Republic of Korea. Electronic address: [email protected].
PMID: 25597012 DOI: 10.1016/j.bmcl.2014.12.082
Abstract

The ethanolic extract of the root of Piper methysticum was found to inhibit melanogenesis in MSH-activated B16 melanoma cells. Flavokawains B and C were isolated from this extract based on their anti-melanogenesis activity and found to inhibit melanogenesis with IC50 values of 7.7μM and 6.9μM, respectively. Flavokawain analogs were synthesized through a Claisen-Schmidt condensation of their corresponding acetophenones and benzaldehydes and were evaluated in terms of their Tyrosinase inhibitory and anti-melanogenesis activities. Compound 1b was the most potent of these with an IC50 value of 2.3μM in melanogenesis inhibition assays using MSH-activated B16 melanoma cells.

Keywords
Chalcones; Flavokawain B and C; Melanogenesis; Piper methysticum.