Identification of N-Hydroxycinnamamide analogues and their bio-evaluation against breast cancer cell lines

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Triple-negative breast cancer (TNBC) remains a significant health challenge due to limited targeted therapies.
• N-hydroxycinnamamide derivatives represent a class of compounds with potential cytotoxic effects.

Purpose of the Study:

• To identify novel N-hydroxycinnamamide derivatives with anticancer potential.
• To evaluate the efficacy of these derivatives against human breast cancer cell lines, including MDA-MB-231 and MCF-7.
• To compare their activity with the established drug Tamoxifen.

Main Methods:

• Synthesis and identification of N-hydroxycinnamamide derivatives.
• In vitro anticancer activity assessment using MTT assays.
• Evaluation of apoptosis induction, DNA fragmentation, and mitochondrial membrane potential changes.

Main Results:

• Compounds 3b and 3h demonstrated significant anticancer activity against MDA-MB-231 cells, with IC50 values of 13μM and 5μM, respectively.
• Compound 3h was found to induce DNA fragmentation and apoptosis.
• Compound 3h also led to the loss of mitochondrial membrane potential and likely initiates reactive oxygen species (ROS) production.

Conclusions:

• N-hydroxycinnamamide derivatives, particularly compound 3h, exhibit promising anticancer properties against triple-negative breast cancer.
• Compound 3h's mechanism involves inducing apoptosis through DNA fragmentation, mitochondrial dysfunction, and ROS generation.