Medicinal Chemistry Research

, Volume 26, Issue 7, pp 1550–1556 | Cite as

Anti-androgenic curcumin analogues as steroid 5-alpha reductase inhibitors

  • Jukkarin Srivilai
  • Karma Rabgay
  • Nantaka Khorana
  • Neti Waranuch
  • Nitra Nuengchamnong
  • Wudtichai Wisuitiprot
  • Thipphawan Chuprajob
  • Chatchawan Changtam
  • Apichart Suksamrarn
  • Warinthorn Chavasiri
  • Nilubon Sornkaew
  • Kornkanok Ingkaninan
Original Research
  • 312 Downloads

Abstract

Anti-androgen can be used in the treatment of benign prostatic hyperplasia, acne, hirsutism, and androgenic alopecia. For the search of anti-androgenic activity through steroid 5-alpha reductase (S5αR) inhibition mechanism, 12 natural analogs from plant origins, i.e., curcumin (1) demethoxycurcumin (2), and bisdemethoxycurcumin (3) isolated from Curcuma longa Linn., compounds 18, 20, 21, 22, 24, and 25 isolated from Curcuma comosa Roxb., amide analogs 2931 obtained from Bougainvillea spectabilis Willd. together with 21 synthesized analogs were evaluated for S5αR inhibitory activity using liquid chromatography–mass spectrometry assay. The results showed that compounds 1, 2, 4, 5, 6, 7, and 9 possessed S5αR inhibitory activity and compounds 1, 4, and 5 were the most potent (IC50 of 13.4 ± 0.4, 15.3 ± 3.1 and 8.9 ± 0.9 µM, respectively). This suggests that the unsaturated enone moiety in the chain linked between two aromatic rings of curcumin analog was imperative to the activity. Moreover, the m-methoxyl and p-hydroxyl substitutions in aromatic region of 1,6-heptadiene-3,5-dione linker were necessary. The cytotoxic effect on androgen-dependent cell, human dermal papilla was investigated to obtain safety information profile. We found that 1,6-heptadiene-3,5-dione linker was important for safety. This work stated that anti-androgen activity of curcumin analogs was through S5αR inhibition mechanism and the information might lead to further design of new curcumin analogs with improved potency and safety.

Keywords

Curcumin analogues Steroid 5-alpha reductase Anti-androgen Dermal papilla 

Abbreviations

S5αR

Steroid 5α-reductase

DHT

Dihydrotestosterone

Notes

Acknowledgements

The authors are grateful for the financial supports from the Royal Golden Jubilee Ph.D. Program (RGJ-Ph.D., Grant No. PHD/0205/2556), The Thailand Research Fund, the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Office of the Higher Education Commission, Ministry of Education and Naresuan University, Thailand. We thank C. Norman Scholfield, Faculty of Pharmaceutical Science, Naresuan University for helping with the manuscript preparation.

Conflict of interest

The authors declare that they have no competing financial interests.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jukkarin Srivilai
    • 1
  • Karma Rabgay
    • 1
  • Nantaka Khorana
    • 1
  • Neti Waranuch
    • 2
  • Nitra Nuengchamnong
    • 3
  • Wudtichai Wisuitiprot
    • 4
  • Thipphawan Chuprajob
    • 5
  • Chatchawan Changtam
    • 6
  • Apichart Suksamrarn
    • 7
  • Warinthorn Chavasiri
    • 8
  • Nilubon Sornkaew
    • 7
  • Kornkanok Ingkaninan
    • 1
  1. 1.Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in ChemistryNaresuan UniversityPhitsanulokThailand
  2. 2.Cosmetics and Natural Products Research Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical SciencesNaresuan UniversityPhitsanulokThailand
  3. 3.Science Laboratory Center, Faculty of SciencesNaresuan UniversityPhitsanulokThailand
  4. 4.Department of Thai Traditional MedicinesSirindhorn College of Public HealthPhitsanulokThailand
  5. 5.Department of Chemistry, Faculty of ScienceSiam UniversityBangkokThailand
  6. 6.Division of Physical Science, Faculty of Science and TechnologyHuachiew Chalermprakiet UniversitySamutprakarnThailand
  7. 7.Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of ScienceRamkhamhaeng UniversityBangkokThailand
  8. 8.Department of Chemistry, Faculty of ScienceChulalongkorn UniversityBangkokThailand

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