Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro.
Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E-dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4-methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease.
Lin
Zhixiu
Z
Department of Pharmacy, King's College London, 150 Stamford Street, London SE1 9NN, UK.
Liao
Yonghong
Y
Venkatasamy
Radhakrishnan
R
Hider
Robert C
RC
Soumyanath
Amala
A
D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002725:Chloroform; D005638:Fruit; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D029222:Piper nigrum / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014820:Vitiligo / Q000188:drug therapy
D000577:Amides; D010936:Plant Extracts; D002725:Chloroform