整合酶（integrase）对于人免疫缺陷病毒（HIV）-1逆转录病毒的复制来说是必不可少的，因而成为抗艾滋病（AIDS）药物设计的一个理性的靶点。最近文献报道了大量具有抗整合酶活性的化合物，当前最大的挑战就是如何将这些作用于整合酶靶点的先导化合物转变成为临床上有效的抗AIDS药物。

Abstract To study the interactions of these compounds with calf thymus DNA(CT-DNA), seven b-carboline-3-carboxamides were designed and synthesized. The interactions of these compounds with CT-DNA were determined by the viscometric titration assay and Tm (melting temperature) value assay. Binding strengths were evaluated by spectrophotometric titration experiment and microcalorimetric measurement. The interactions of these compounds were tested with CT-DNA. It was showed that all of these compounds were able to change the Tm value of CT-DNA. The results of viscometric titration assay indicated that these compounds interacted with CT-DNA by intercalation. Spectrophotometric titration experiment showed that the binding strengths of these compounds with CT-DNA were different, which was well in agreement with the cell culture results. The binding was driven by entropy according to the results of the microcalorimetric measurement. This series of b-carboline-3-carboxamides is DNA targeting compounds. Their obvious antitumor biological effect is based on the intercalation with DNA base-pairs.

Aseries of bleomycin analogues was prepared with a facile synthetic method. All the compounds were shown to display significant antitumor activity against HeLa and BGC-823 cell lines in vitro. The binding properties with CT-DNAand cleavage efficiency to pBR322 DNAwere investigated, the results indicate that there is a positive relationship between DNAcleavage efficiency and the binding affinity to DNA, and the antitumor activity of the bleomycin analogues is enhanced as the hydrophobicity of the C-terminus substituent side chain increased.

Synthesis of unimolecularly circular G-quadruplex has been accomplished for the first time during our investigation on the template basis of G-quadruplex through chemical ligations of guanine-rich linear sequencesofoligodeoxyribonucleotides. Theuniqueness of this newly designed circularization course is its self-recognition and self-templating on the scale of individual strand of zligodeoxyribonucleotide in which the same linear sequence serves both as a template and as a substrate simultaneously. The results from our exonuclease and DNAse hydrolysis studies confirm that there is indeed absence of open termini within the structure of the identified circular product. Our subsequent investigation on the loopsize effect indicates that the unimolecularly circular G-uadruplex possessing two or more thymine nucleotides within their connecting loops is readily attainable, while the linear sequence with a single thymine nucleotide between guanine tracts is not a proper precursor for our ligation reaction. In addition, conformation dependency of the circularization course as well as the effects of alkali ions, pH values and concentration of potassium ions on the circularization reaction are examined during our investigation. The implication of our current studies and possible application of the obtained unimolecularly circular G-quadruplex in certain biological processes are also discussed in this report.

The complex [Mn(L)(NO) (HO)] (1) (L52H-5-hydroxy-1, 2, 5-oxadiazo[3, 4-f]1,10-phenanthroline) was synthesized and character-3222 ized by elemental analysis, IR and UV. The crystal and molecular structure of 1 was determined by single-crystal X-ray diffraction; crystal data: light yellow, monoclinic, space group P2/n, Z54, a 57.432 (2) A, b59.582(3) A, c 523.445(7) A, b 590.519 (5)8. The Mn atom in 11 is hexa-coordinated in a distorted octahedral arrangement by two N atoms of the ligand L and four O atoms of two water molecules and two nitrate anions. Biological tests in vitro showed that 1 has significant antitumor activity against HL-60, KB, Hela and BGC-823 cells. The interaction of 1 with calf thymus DNA was investigated by absorption titration, thermal denaturation and viscosity measurements. The results suggest that 1 binds with DNA by intercalating via the ligand L.