Synthesis and Cytotoxic Evaluation of Novel Symmetrical Taspine Derivatives as Anticancer Agents

Abstract

It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC₅₀ values between 19.41 µM and 29.27 µM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the relationship between structure and activity based on the experimental results. Our findings provide a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.

A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways

“…HMQ1611 suppresses breast cancer cell growth HMQ1611 was synthesized as described previously (37). To assess the effects of HMQ1611 on breast cancer cell growth, breast cancer cells (MDA-MB-231, SK-BR-3, MCF-7, and ZR-75-30) were treated with HMQ1611 at 0, 2, 10, 50 mmol/L concentrations.…”

“…With the biologic assay screens of taspine derivatives, we found that compound HMQ1611 (Fig. 1A) exhibits the most potent pharmacologic effects (37). In this study, we further characterized the anticancer effects of HMQ1611 in 4 breast cancer cell lines and an in vivo mouse model.…”

“…Previously, we found that taspine displayed good affinity characteristics in a cell membrane chromatography model stably overexpressing EGFR (34) and could be used as a lead compound for searching novel anticancer agents. We have designed and synthesized a series of ring-opened and biphenyl taspine derivatives with increasing activity and solubility (35)(36)(37). With the biologic assay screens of taspine derivatives, we found that compound HMQ1611 (Fig.…”

Genus Caulophyllum: An Overview of Chemistry and Bioactivity

“…To further investigate this finding, researchers aimed to enhance the structural complexity and diversity of 22′ by generating novel biphenyls (Figure 4) [41]. As a result, eighteen symmetrical biphenyls derivatives (31′–48′) were firstly prepared [42]. Following these, He et al used 20′ as the identifying group and synthesized another two novel taspine diphenyl derivatives 49′ and 50′, which were made by introducing coumarin groups into the structure of 20′ [43].…”

“…Derivatives (31′) and (32′) demonstrated the most potent cytotoxic activity with IC 50 values between 14.2  μ g/mL and 22.3  μ g/mL among symmetrical taspine derivatives (31′–48′) [42]. Biphenyls without halogen substitution (34′, 38′, 39′, and 44′) were much less potent than those containing halogen.…”