| Summary: | 博士 === 高雄醫學大學 === 藥學研究所博士班 === 92 === (I)
The present report describes the synthesis and evaluation of
tricyclic benzo[g]quinolin-4(1H)-one derivatives (CAB type) in which
an additional aromatic ring is linearly fused on the antibacterial
quinolone-3-carboxylic acid to maintain a free carboxylic acid (increase
water-solubility) and a coplanar tricyclic DNA-intercalating
chromophore (improve antitumor activity). 1H-Benzo[g]Quinoline
-4,5,10-trione (2), 1-methyl-1H-benzo[g]quinoline-4,5,10-trione (3), and
ethyl 1-methylbenzo[g]quinoline-4,5,10-trione- 3-carboxylate (5)
exhibited significant cytotoxicity against all 60 cancer cells with mean
GI50 values of 5.92, 7.75, and 2.52µM respectively while
1-methylbenzo[g]quinoline-4,5,10-trione-3-carboxylic acid (8) and
5-hydroxy-10-methoxy-1-methylbenzo[g]quinoline-4(1H)-one-3-carbox
ylic acid (12) were inactive, indicated free carboxylic acid at C-3
position is unfavorable. The results have also implied the importance of
carbonyl moieties at C-5 and C-10 due to the inactiveness of reduced
products ethyl 5-hydroxy-10-methoxy-1- methylbenzo[g]quinoline-
4(1H)-one-3-carboxylate (9), and ethyl 10-benzyloxy- 5-hydroxybenzo
[g]quinoline-4(1H)-one-3-carboxylate (10).
(II)
Isoflavonoids are a ubiquitous family of phytochemicals that
possess a wide variety of biological activities including anticancer,
antioxidant, anti-inflammatory, gastroprotective, antiviral, antimutagenic
activities, etc. However, diversed biological activities sometimes are
disadvantageous because other biological effects will become side
effects when these compounds are used as, for example, anticancer
drugs. In general, the substituents on isoflavoniods and their
conformations will affect the biological activities. The present report
describes the preparation and anticancer evaluation of conformationally
locked isoflavone derivatives in which the phenyl and the chromone
rings are linked by a six-membered ester ring. To optimize the anticancer
activities and improve water solubility of these conformationally locked
isoflavone derivatives, Mannich bases and the isosteric isomers have
also been prepared for evaluation.
Among them, 9-[2-(4-chlorophenyl)- 2-hydroxyiminoethoxy]
chromeno[3,4-b]chromen-6,12-dione(8c) exhibits selective cytotoxicity
against K526(GI50 = 1.99 µM), F-295(GI50 = 1.99 µM), RXF393(GI50 =
2.13 µM), and DA-MB-435(GI50 = 2.45 µM).
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