Syntheses and bioactivities of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines.
A number of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones have been synthesized and their anticancer and antimalarial activities evaluated. A one-pot synthesis of 2,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione (4) was achieved by heating a mixture of 1,4-dimethoxyanthracene, methoxyhydroquinone, silver oxide, and zinc iodide in toluene. Regioselective bromination of 4 and 2-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (7) with N-bromosuccinimide provided 2-bromo-3,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione and 2-bromo-3-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (1), respectively. The reactions of 1 with aliphatic primary amines and secondary amines, respectively, produced different products, a result most likely attributed to the different basicities (or nucleophilicities) and steric effects of the two kinds of amines. The structure of the displacement product, 2-bromo-3-[2-(tert-butoxycarbonyl)ethylamino]-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone, from the reaction of 1 with tert-butyl 3-aminopropanoate was unequivocally determined by a single-crystal X-ray analysis. IC(50) values of triptycene bisquinones for the inhibition of L1210 leukemia cell viability are in the 0.11-0.27 microM range and for the inhibition of Plasmodium falciparum 3D7 are in the 4.7-8.0 microM range.
Hua
Duy H
DH
Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, USA. duy@ksu.edu
Tamura
Masafumi
M
Huang
Xiaodong
X
Stephany
Heidi A
HA
Helfrich
Brian A
BA
Perchellet
Elisabeth M
EM
Sperfslage
Bonnie J
BJ
Perchellet
Jean-Pierre
JP
Jiang
Suping
S
Kyle
Dennis E
DE
Chiang
Peter K
PK
D000588:Amines / Q000737:chemistry*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007938:Leukemia; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
C463559:2,5,8-trimethoxy-9,10-dihydro-9,10-(1,2)benzenoanthracene-1,4-dione; C463561:2-bromo-3-methoxy-9,10-dihydro-9,10-(1,2)benzenoanthracene-1,4,5,8-tetrone; C463560:2-methoxy-9,10-dihydro-9,10-(1,2)benzenoanthracene-1,4,5,8-tetrone; D000588:Amines; D000962:Antimalarials; D000970:Antineoplastic Agents; D001551:Benz(a)Anthracenes; D006842:Hydrocarbons, Brominated