ABSTRACT

The estimated number of breast cancer fatalities among women worldwide in 2020 was 6,85,000, or 15% of all cancer deaths among women. In India, there were an estimated 1,78,361 new cases and 90,408 deaths from the disease, according to Global statistics in 2020. Breast cancer is one of the second most common cancer in India and causes the greatest number of cancer-related deaths among women. The development of multi-drug resistance and undesirable side effects leads to investigating the new anticancer agents. In order to overcome the new cancers, the present work focussed on to develop some novel anti-breast cancer agents. The study involved “In-silico design, synthesis and study of novel N-substituted phthalimide derivatives for its anti-cancer activity against targeted enzymes in breast cancer. The purity of synthesized compounds was determined by melting point determination and thin layer chromatography. The structures of the synthesized compounds were characterized using FT-IR, 1H-NMR, 13C-NMR and Mass spectral analysis. Molinspiration software were used to study the Drug likeness properties of the synthesized compounds. All the synthesized compounds obeyed the Lipinski rule of Five. SWISS ADME online web tool was used to predict the in silico ADME studies and OSIRIS property explorer were used to study the toxicity profile. Molecular docking studies for all the designed compounds were doneusing Autodock software version 4.2 against the various target enzymes such as Dihydrofolate reductase, Poly (ADP-Ribose) polymerase and Epidermal Growth factor receptor. The compound DPAL showed best binding energy of 10.24&-9.31 kcal/mol when compared to the binding energy of standard Methotrexate -4.44 and Talazoparib-6.59 kcal/mol against the target Dihyrofolate reductase (DHFR) and Poly (ADP-ribose) polymerase(PARP-I).The compound DPSML showed best binding energy of -8.37 kcal/mol compared with the standard Lapatinib -6.99 kcal/mol against the Epidermal growth factor receptor (EGFR).The present research study showed promising response in the molecular docking studies against the targeted enzyme in breast cancer. Hence, this research work will be further continued by designing few more novel analogues and study of its potential against the targeted enzyme for its anticancer activity against the breast cancer cell lines. Keywords: Phthalimide, Breast cancer, Molecular docking, Dihydrofolate reductase, Epidermal growth factor receptor, Autodock4.2
Publication date: 01/02/2025

https://ijbpas.com/pdf/2025/February/MS_IJBPAS_2025_8708.pdf

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https://doi.org/10.31032/IJBPAS/2025/14.2.8708