Synthesis of novel, DNA binding heterocyclic dehydroabietylamine derivatives as potential antiproliferative and apoptosis-inducing agents

Abstract

Several dehydroabietylamine derivatives containing heterocyclic moieties such as thiophene and pyrazine ring were successfully synthesized. The antiproliferative activities of these thiophene-based Schiffbases, thiophene amides, and pyrazine amides were investigated in vitro against Hela (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver), and HUVEC (umbilical vein) cells by MTT assay. The toxicity of L 1 ÀL 10 (IC 50 ¼ 5.92À >100 lM) was lower than L 0 (1.27 lM) and DOX (4.40 lM) in every case. Compound L 1 had higher anti-HepG2 (0.66 lM), anti-MCF-7 (5.33 lM), and anti-A549 (2.11 lM) and compound L 3 had higher anti-HepG2 (1.63 lM) and anti-MCF-7 (2.65 lM) activities. Both of these compounds were recognized with high efficiency in apoptosis induction in HepG2 cells and intercalated binding modes with DNA. Moreover, with average IC 50 values of 0.66 and 5.98 lM, L 1 was nine times more effective at suppressing cultured HepG2 cells viability than normal cells (SI ¼ 9). The relative tumor proliferation rate (T/C) was 38.6%, the tumor inhibition rate was up to 61.2%, which indicated that L 1 had no significant toxicity but high anti-HepG2 activity in vivo. Thus, it may be a potential antiproliferation drug with nontoxic side effects.

Research on Anthocyanins from Rubus “Shuofeng” as Potential Antiproliferative and Apoptosis-Inducing Agents

“…ROS can represent a new standard for determining cytotoxicity because increasing intracellular ROS interferes with the oxidative environment of cells and induces cell death [ 32 ]. In vivo experiments have indicated that anthocyanins can prevent and treat cancer, with the relative tumor proliferation rate (T/C) being 44.67% and the tumor inhibition rate being 52.76%, similar to our previous paper covering the anticancer activity of natural products and suggesting that it has excellent antiproliferative effects [ 29 , 35 ]. The further mechanism might be that S 1 can induce apoptosis by interacting with DNA in an intercalation mode, changing or destroying DNA.…”

“…However, after adding DNA, the fluorescence intensity significantly increased due to the strong insertion of DNA base pairs. The compound’s intercalation into the DNA base pair was confirmed when fDNA-EB emission was reduced or quenched after adding the compound [ 34 , 35 , 36 ].…”

The Extraction and High Antiproliferative Effect of Anthocyanin from Gardenblue Blueberry

“…After adding DNA, the fluorescence intensity improved, which was considered to be due to its strong intercalation with DNA base pairs. The intercalation of the compound with the base pairs of DNA was confirmed when the fDNA-EB emissions were decreased or quenched upon adding a compound [ 41 , 42 , 43 ]. As expected, the emission intensity reduced (shown in Figure 7 ) by adding L 1 to fDNA-EB, which showed that L 1 can bind to DNA at the sites occupied by EB and that it can interact with DNA via intercalation.…”

Polyphenols fromPrunus mume: extraction, purification, and anticancer activity

“…Cell viability values were determined (at least three times) according to the following equation: cell viability (%) = the absorbance of the experimental group/the absorbance of the blank control group × 100%. [35][36][37] Induction of apoptosis by flow cytometric analysis in vitro. Induction apoptosis assay was performed using a Becton Dickinson Ultra-high speed separation flow cytometry instrument and Annexin V-FITC/PI was purchased from Beyotime Biotechnology Co. Ltd.…”