光谱学与光谱分析
光譜學與光譜分析
광보학여광보분석
SPECTROSCOPY AND SPECTRAL ANALYSIS
2014年
11期
3051-3055
,共5页
呋喃香豆素%“最小嵌入”%类呋喃香豆素%DNA%抗肿瘤
呋喃香豆素%“最小嵌入”%類呋喃香豆素%DNA%抗腫瘤
부남향두소%“최소감입”%류부남향두소%DNA%항종류
Furocoumarin%“Minimal DNA-intercalating”%Pseudo-furocoumarin%DNA-binding%Antitumor
呋喃香豆素类化合物无紫外光辅助照射时抗肿瘤活性低，为提高其正常情况下的抗肿瘤活性，依据“最小嵌入”假说对其进行结构改造。把呋喃香豆素结构中的呋喃环拆分出来，使其与香豆素由原来稠环相并的结合方式转变为通过化学键相连，得到合成简化的类呋喃香豆素。利用DNA熔解曲线、吸收光谱、荧光发射光谱和粘度测试考察了这些类呋喃香豆素与DNA的相互作用。综合DNA溶解曲线、光谱法和粘度测试的结果，推测除目标产物5b是一DNA嵌入剂外，其他化合物嵌入DNA能力下降，5a以部分嵌入方式与DNA结合，5c和5d是通过极为少见、鲜有报道的“桥型结构”与DNA相结合。利用“罗丹明B蛋白染色法”考察了目标化合物的体外细胞毒性，测试结果显示，与对照品补骨脂素相比这些化合物对肿瘤细胞体外生长抑制作用明显增强，并且非经典嵌入结合的化合物活性增强更明显。该研究拓展了“最小嵌入”假说的应用范围，同时为呋喃香豆素类化合物结构改造提供了依据。
呋喃香豆素類化閤物無紫外光輔助照射時抗腫瘤活性低，為提高其正常情況下的抗腫瘤活性，依據“最小嵌入”假說對其進行結構改造。把呋喃香豆素結構中的呋喃環拆分齣來，使其與香豆素由原來稠環相併的結閤方式轉變為通過化學鍵相連，得到閤成簡化的類呋喃香豆素。利用DNA鎔解麯線、吸收光譜、熒光髮射光譜和粘度測試攷察瞭這些類呋喃香豆素與DNA的相互作用。綜閤DNA溶解麯線、光譜法和粘度測試的結果，推測除目標產物5b是一DNA嵌入劑外，其他化閤物嵌入DNA能力下降，5a以部分嵌入方式與DNA結閤，5c和5d是通過極為少見、鮮有報道的“橋型結構”與DNA相結閤。利用“囉丹明B蛋白染色法”攷察瞭目標化閤物的體外細胞毒性，測試結果顯示，與對照品補骨脂素相比這些化閤物對腫瘤細胞體外生長抑製作用明顯增彊，併且非經典嵌入結閤的化閤物活性增彊更明顯。該研究拓展瞭“最小嵌入”假說的應用範圍，同時為呋喃香豆素類化閤物結構改造提供瞭依據。
부남향두소류화합물무자외광보조조사시항종류활성저，위제고기정상정황하적항종류활성，의거“최소감입”가설대기진행결구개조。파부남향두소결구중적부남배탁분출래，사기여향두소유원래주배상병적결합방식전변위통과화학건상련，득도합성간화적류부남향두소。이용DNA용해곡선、흡수광보、형광발사광보화점도측시고찰료저사류부남향두소여DNA적상호작용。종합DNA용해곡선、광보법화점도측시적결과，추측제목표산물5b시일DNA감입제외，기타화합물감입DNA능력하강，5a이부분감입방식여DNA결합，5c화5d시통과겁위소견、선유보도적“교형결구”여DNA상결합。이용“라단명B단백염색법”고찰료목표화합물적체외세포독성，측시결과현시，여대조품보골지소상비저사화합물대종류세포체외생장억제작용명현증강，병차비경전감입결합적화합물활성증강경명현。해연구탁전료“최소감입”가설적응용범위，동시위부남향두소류화합물결구개조제공료의거。
Furocoumarin shows some antitumor activity when it is radiated by the UV light .In order to improve the antitumor activity of furocoumarin under standard environment conditions ,the“minimal DNA-intercalating” hypothesis was firstly intro-duced to the structural modification of furocoumarin ,which resulted in the design of pseudo-furocoumarin .The pseudo-furocou-marin was synthesized by two-step reaction including Pechmann reaction catalyzed by conc .H2SO4 and Suzuki coupling reaction catalyzed by Pd(PPh3 )4 .The structural character of the pseudo-furocoumarin is that the bonding mode of furan ring fused to the coumarin is replaced by a chemical single bond between furan ring and coumarin .The interaction of the pseudo-furocoumarin with calf thymus DNA (CT-DNA) has been respectively investigated by using DNA melting curve ,UV-Vis absorption spectra , fluorescence spectra and viscosity titration ,and the modes of DNA-binding for the pseudo-furocoumarin have been proposed . Based on the results of DNA melting curve ,spectra and viscosity titration ,it was suggested that 5a and 5b bind to DNA by the partial intercalation and classical intercalation ,respectively .The DNA-binding behaviors of 5c and 5d have been rarely reported in literature and may be interpreted in terms of bridge-structure .All target compounds ,except 5b ,show a decreasing capability of intercalation to DNA .Further ,the antiproliferative activities of the pseudo-furocoumarin on human lung adenocarcinoma (A549) ,human breast cancer (MCF-7) and human ovarian carcinoma cell line (SKOV-3) in vitro were evaluated using the sul-forhodamine B (SRB) protein statin assay .All pseudo-furocoumarin exhibited an improved anti-proliferative activity as compared with the control compound psoralen (PS ,a linear furocoumarin) .Interestingly the pseudo-furocoumarin binding to DNA by a non-classical intercalation mode showed a stronger anti-proliferative activity than PS .The present study extended the applied areas of “minimal DNA-intercalating”hypothesis ,and provided a method for the structural modification of furocoumarin as well .
