Novel Thymoquinone Derivative TQFL28 Inhibits Triple-Negative Breast Cancer (TNBC) Invasiveness In Vitro and In Vivo

Area of Science:

• Medicinal Chemistry
• Oncology
• Pharmacology

Background:

• Thymoquinone (TQ) is a known anti-tumor agent with broad applicability.
• Triple-negative breast cancer (TNBC) remains a challenging subtype with limited therapeutic options.

Purpose of the Study:

• To design and synthesize a novel TQ derivative, TQFL28.
• To evaluate the anti-cancer efficacy and toxicity of TQFL28 against TNBC.

Main Methods:

• Synthesis of TQFL28 (C20H23NO2).
• In vitro cytotoxicity and anti-proliferative assays using TNBC cell lines (BT549, MDA-MB-231, 4T1) and normal cells (MCF10A).
• In vivo studies using a 4T1 allograft mouse model to assess tumor progression, metastasis, and toxicity (LD50).

Main Results:

• TQFL28 exhibited superior cytotoxicity and anti-proliferative effects against TNBC cell lines compared to TQ, with lower IC50 values.
• TQFL28 effectively inhibited TNBC cell growth, migration, and invasion in vitro.
• In vivo, TQFL28 reduced tumor volume and progression in a TNBC mouse model with lower observed toxicity than TQ (LD50 = 59.43 mg/kg).

Conclusions:

• TQFL28 is a potent novel small molecule derivative of thymoquinone.
• TQFL28 demonstrates significant therapeutic potential for treating triple-negative breast cancer with an improved safety profile.