Synthetic DNA-intercalator Naphthalimide-artesunate Hybrid Drug Potential Reactive Oxygen Species-generator against Breast Cancer

Background: Breast cancer therapeutics faces challenge due to the heterogeneity of solid tumors. Thus, emergent need for the development of small molecule to overcome problems associated with drug resistance and prognosis rate against breast cancer is required. Objective: This study aimed to look into the potential of asynthesized hybrid drug based on repurposing of known antimalarial drug artesunate (ARTN) followed by remodelling via conjugation with azido-substituted naphthalimide. The synthesized conjugate naphthalimide-artesunate has already proven its ability against the growth of lymphoma in in vitro and in vivo solid Dalton’s lymphoma (DL) tumor in BALB/c mice. To further determine the anti-breast cancer activity of azide-naphthalimide-artesunate, the compound was screened in different human breast carcinoma cell like, MDA-MB-231 (TNBC) with high metastatic potential, MCF-7 (luminal A) and murine origin 4T1 breast carcinoma cell in vitro along with further determination of mechanism of action of the synthesized drug molecule. Materials and Methods: Cytotoxicity assay, cellular uptake, cell cycle arrest, apoptosis and ROS generation were performedthrough FACS and microscopy to compare the effects of the synthesized molecules to artesunate against breast cancer. Results: The synthesized molecule naphthalimide-artesunate conjugate enables induction of G0/G1 arrest through production of ROS and lead to apoptosis. Interestingly, it has been also noticed that the conjugate has higher sensitivity towards MDA-MB-231-metastatic breast cancer cell line. Conclusions: The synthesized compound represents promisingtumoricidal activity along with enhanced cellular uptake, cell cycle arrest, apoptosis and ROS generation compared to artesunate and demand further extensive research against various cancers.