Breast cancer has the largest prevalence and third mortality rate among all cancer cases in the world. Drug resistance has been a major problem, urging the need for drug discovery. Various studies have shown several active substances from natural ingredients that can inhibit the invasion and migration of cancer cells, including Zerumbone contained in Lempuyang (Zingiber zerumbet). However, no study has been made to explore the molecular targets of Zerumbone in breast cancer. The purpose of this study is to find potential molecular targets of Zerumbone in silico. Bioinformatic analysis was conducted with STITCH and STRING to get direct and indirect target proteins of Zerumbone, respectively. The resulting target proteins were selected according to the NCBI database of breast cancer stem cell regulatory genes using a Venn Diagram. Eighty-three Zerumbone target proteins in breast cancer cells were obtained. Then, their degree in biological interaction was assessed and ranked with STRING and Cytohubba. Six molecules from the top 20 targets (AKT1, XIAP-BIR2, XIAP BIR-3, HSP90AA1, MDM2, and EP300) were then used as targets for molecular docking of Zerumbone, performed with Autodock 1.5.6. Molecular docking revealed that Zerumbone binds all tested targets with low binding energy, indicating that Zerumbone can have multi-targets in combating cancer.

The development of environmentally sustainable synthetic approaches for biologically active heterocyclic compounds has become increasingly important in medicinal chemistry. In this study, two dihydropyrimidinone (DHPM) derivatives were synthesized through a green Biginelli multicomponent reaction using Phyllanthus acidus fruit extract as a natural acid catalyst. The synthesized compounds were characterized by UV-Vis, FT-IR, ¹H NMR, and ¹³C NMR analyses. The effects of the volume of the catalyst on product yield were investigated, revealing optimal conditions of 3 and 7 mL, respectively, for DHPM-1 and DHPM-2. The biological potential of the synthesized compounds was evaluated through molecular docking, molecular dynamics simulation, and in vitro cytotoxicity assays against A549 cell lines. Molecular docking predicted moderate binding affinities of −5.8 and −5.5 kcal mol⁻¹ for DHPM-1 and DHPM-2, respectively, compared with −7.5 kcal mol⁻¹ for doxorubicin. Consistent with the computational results, DHPM-1 and DHPM-2 exhibited weak cytotoxic activity with IC₅₀ values of 156.395 and 447.205 µg/mL, respectively. These findings indicated that although the present DHPM derivatives possess limited anti-lung cancer activity, the developed green synthetic strategy provides a route associated with lower environmental impact for preparing DHPM scaffolds that may serve as promising starting points for further structural optimization and biological investigation.

Cancer has high prevalence to cause a mortality in the world in case of breast cancer, although numerous medical treatment have been developed. Cancer treatment and therapy failures are frequently caused by drug resistance and toxicity. Therefore, efforts to develop and discover renewed cancer drugs still have an enormous attention to improve effectiveness of bioavailability. Potential of natural products as an anti-cancer has been reported, especially zerumbone through antiproliferation, antiapoptotic, and antimetastatic mechanism. Zerumbone, a phytochemical sesquiterpenoid with cyclic ketone as a main building block, isolated from Zingiber zerumber Smith (lempuyang wangi). A number of derivates of zerumbone have been reported using in silico method to obtain potential candidate of breast cancer. Focus of our research to predict derivatives of zerumbone with the best pharmacokinetic properties and the best interaction with main breast cancer targets. Further, molecular docking with autodock were conducted to predict the interaction with breast cancer target. Our protein target docking are EP300 (E1A Binding Protein P300) and HER2 (Human Epidermal Growth Factor Receptor 2) that roles to accelerate breast cancer cells growth. Twenty one zerumbone derivatives have been determined for molecular docking in silico study. Assesment of binding energy showed that five zerumbone derivatives have higher interaction with EP300 compared to zerumbone (-5,01 kcal/mol). In addition, more than half of examined zerumbone derivatives have higher stability over HER2 than zerumbone (-5,92 kcal/mol) based on calculated binding affinity.