Gopal M, Shenoy S, Doddamani L S
Department of Biochemistry, Kuvempu University, Shivagangotri, Davangere 577 002, India.
J Photochem Photobiol B. 2003 Dec 5;72(1-3):69-78. doi: 10.1016/j.jphotobiol.2003.09.003.
The interaction of 4-aminopyrimido [4',5':4,5] thieno (2,3-b) quinoline and 8-methyl-4-(3-diethylaminopropylamino) pyrimido [4',5':4,5] thieno (2,3-b) quinoline with DNA was studied by UV-Vis and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectra underwent bathochromic and hypochromic shifts and the fluorescence was quenched. These compounds are able to bind to DNA with an affinity of about 10(6) M(-1) for calf thymus DNA at ionic strength 0.01 M and their intercalating characteristic (lengthening of the DNA) depends upon the length of the chain. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA at ionic strength 0.01 M. The cytotoxicities of these compounds on leukemia HL-60, melanoma B16F10 and neuro 2a cells are quite similar and inhibition (IC50) is in the range of 0.992-3.968 microM. The anticancer efficacy against B16 melanoma, has provided evidence of major antitumor activity for 8-methyl-4-(3diethylaminopropylamino) pyrimido [4',5':4,5] thieno(2,3-b)quinoline. Single or multiple intraperitonial (i.p) doses of drug proved high level activity against the subcutaneous (s.c) grafted B16 melanoma, significantly increasing survival (p<0.001) and inhibiting tumor growth (T/C of 4%). This study offers a new intercalation functional group to DNA-targeted drug design.
采用紫外可见分光光度法、荧光分光光度法以及流体动力学方法研究了4-氨基嘧啶并[4',5':4,5]噻吩并(2,3-b)喹啉和8-甲基-4-(3-二乙氨基丙基氨基)嘧啶并[4',5':4,5]噻吩并(2,3-b)喹啉与DNA的相互作用。与DNA结合时，吸收光谱发生红移和减色位移，荧光被猝灭。在离子强度为0.01 M时，这些化合物能够以约10(6) M(-1)的亲和力与小牛胸腺DNA结合，其嵌入特性（DNA长度增加）取决于链的长度。在离子强度为0.01 M时，与溶壁微球菌富含GC的DNA的结合比与小牛胸腺DNA的结合更强。这些化合物对白血病HL-60、黑色素瘤B16F10和神经2a细胞的细胞毒性非常相似，抑制率（IC50）在0.992 - 3.968 microM范围内。对B16黑色素瘤的抗癌疗效证明了8-甲基-4-(3-二乙氨基丙基氨基)嘧啶并[4',5':4,5]噻吩并(2,3-b)喹啉具有主要的抗肿瘤活性。单次或多次腹腔内（i.p）给药的药物对皮下（s.c）移植的B16黑色素瘤具有高水平活性，显著提高生存率（p<0.001）并抑制肿瘤生长（T/C为4%）。本研究为靶向DNA的药物设计提供了一个新的嵌入官能团。
