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.
Tat, an essential human immumodeficiency virus type 1 protein interacts with the transactivation response element(TAR) and stimulates transcription from the viral long-terminal repeat(LTR). Blockage of Tat-TAR interaction halts viral transcription and hence replication. In recent years a numbe of studies have suggested various chemicals and /or genetic inhibitors targeting TAR RNA for inhibition of Tat-activated transcription. Here, we report these research works.
