Synthesis, Characterization, and Anticancer Activity of New Quinazoline Derivatives against MCF-7 Cells

Abstract

Two new synthesized and characterized quinazoline Schiff bases 1 and 2 were investigated for anticancer activity against MCF-7 human breast cancer cell line. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an IC50 value of 6.246 × 10−6 mol/L and 5.910 × 10−6 mol/L, respectively, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with 1 and 2 subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS formation. We also found activation of caspases-3/7, -8, and -9 in compounds 1 and 2. Moreover, inhibition of NF-κB translocation in MCF-7 cells treated by compound 1 significantly exhibited the association of extrinsic apoptosis pathway. Acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed significant activity towards MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway and are potential candidate for further in vivo and clinical breast cancer studies.

Current research on anti-breast cancer synthetic compounds

“…28 Two new synthesized and characterized quinazoline Schiff bases 22 and 23 showed a remarkable antiproliferative effect for MCF-7 human BC cell line, with an IC 50 value of 6.246 mM and 5.910 mM, respectively, through inducing apoptosis pathway, activating caspases-3/7, -8, and -9 and inhibiting NF-B translocation (Table 2). 29 Two novel series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives as EGFR/HER2 dual inhibitors were synthesized and subjected to pharmacological evaluation. Compounds 24 and 25 with IC 50 value of 2.3 mM and 0.47 mM respectively had well exhibition to the EGFR and HER2 inhibition activity and excellent anti-proliferation activity against human lung adenocarcinoma cell line (A549) and human BC cell line (SK-Br3) comparing with lapatinib (Table 2).…”

Synthesis of 2-Substituted Benzothiazole Derivatives and Their In Vitro Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells

“…Apoptosis is regarded as a crucial element of several processes including normal cell turnover, however, in cancer cells, the process is suppressed and required to be triggered, which is an important mechanism of action of anticancer agents (3,4). Consequently, cancer drugs have been developed that can lead to apoptotic death through a tumorsuppressor protein-dependent pathway (5).…”

New Quinazolinone Derivatives: Sythesis and in Vitro Cytotoxic Activity

“…Some quinazolinone derivatives (6-10) ( Fig. 2) were proved substantial in treating human leukemia than the conventional agents, and showed the significant effect of quinazolinones derivatives against breast cancer cell lines [19][20][21][22]. Accordingly, in our continuous program for the search of novel anti-cancer agents, we continue to focus on the synthesis of new quinazolinone derivatives, and evaluate the cytotoxic effects on some cancer cell lines.…”