title: Melanogenesis-Inhibitory Activities of Isomeric C-seco Limonoids and Deesterified Limonoids.
abstract: Treatment of eight C-seco limonoids including six of salannin-type, 1 - 6, and two of nimbin-type, 7 and 8, with a combination of BF3· Et2O and iodide ion yielded the isomeric C-seco derivatives, i.e., six isosalannins, 1a - 6a, and two isonimbins, 7a and 8a, respectively. Ohchinin (1) was further subjected to LiAlH4reduction which yielded a deesterified trihydroxy limonoid, nimbidinol (9). In addition, ten limonoids including seven of azadirone-type, 10 - 16, and three of gedunin-type, 17 - 19, all of which possess no ester functionality in the molecule, were obtained from the neutral fraction of Azadirachta indica seed extract after alkaline hydrolysis. Among the above, twelve compounds, i.e., 1a - 4a, 6a, 9, 13 - 16, 18, and 19, were new compounds, and their structures were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluation of all these limonoids for their inhibitory activities against melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), five structurally modified limonoids, 3-deacetyl-28-oxosalannin (6a), 9, 17-epi-17-hydroxynimbocinol (14), 17-epi-17-hydroxy-15-methoxynimbocinol (15), and 7-deacetyl-17-epinimolicinol (18), in addition to a natural limonoid, 1, exhibited potent inhibitory activities with 26 - 66% reduction of melanin content at 100 μm concentration with almost no or low toxicity to the B16 melanoma cells (70 - 99% cell viability at 100 μm).
authors.affiliation: Akihisa Medical Clinic, 1086-3 Kamo, Sanda-shi, Hyogo, 669-1311, Japan. akihisa_toshihiro@yahoo.co.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Horiuchi
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ogihara
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Natural Medicine Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001156:Artemia / Q000187:drug effects; D031601:Azadirachta / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D036701:Limonins; D008543:Melanins
keywords: C-seco Limonoids; Deesterified limonoids; Isomeric C-seco limonoids; Melanogenesis-inhibitory activity