Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity

Abstract

The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools. The compounds demonstrated promising anti-cancer activity for the MCF-7 breast cancer cell line (GI = 6–63%). The compound with the highest activity (6j) was selective for the MCF-7 breast cancer cell line (IC50 = 17.01 μM) with no effect on the MCF-12A normal breast cell line supported by real-time cell analysis. A morphological examination of the used cell lines confirmed a cytostatic effect of compound 6j. It inhibited both in vivo and in vitro estrogenic activity, triggering a 38% reduction in uterine weight induced by estrogen in an immature rat model and hindering 62% of ER-α receptors in in vitro settings. In silico molecular docking and molecular dynamics simulation studies supported the stability of the ER-α and compound 6j protein–ligand complex. Herein, we report that indolin-2-one derivative 6j is a promising lead compound for further pharmaceutical formulations as a potential anti-breast cancer drug.

Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells

“…Cells were incubated with compounds for 72 hours at 37 °C and 5% CO 2 . Subsequently, cells were photographed for morphological change assessment under an inverted microscope, a Leica DM IL LED with a DFC-290 camera (Leica, Wetzlar, Germany) [ 59 ].…”

Gene expression and anticancer evaluation of Kigelia africana (Lam.) Benth. Extracts using MDA-MB-231 and MCF-7 cell lines

“…The early stage of cancer development is associated with inflammation while later stages have metastasis, progression, and relapse. Among many factors, genetic mutation is the dominant cause but among other reasons, alcohol consumption, obesity, and smoking also accelerate the progression of cancerous tumours to the advanced stages which become untreatable eventually [ 5 ]. Numerous mutated genes play a role in breast cancer proliferation, of which TP53 (Tumour Protein 53), is the most well-known mutant gene implicated in several cellular signals that include blood vessel formation, cell cycle regulation, metabolic reactions, and nucleic acid repair.…”

Design, synthesis, molecular docking and biological evaluation of 1,2,4-triazole derivatives possessing a hydrazone moiety as anti-breast cancer agents

“…One of the principal strategies for drug discovery of new drug candidates is to amalgamate two or more pharmacophoric moieties in a single molecule to achieve the synergistic effect or obtain anticancer agents via a novel mechanism of action. In light of the afore-mentioned facts and continuation of our previous studies on identifying new antiproliferative activities, 16,23–26 hybrid compounds containing a 1,2,4-triazole ring and a hydrazone moiety were synthesized by employing an iodine mediated reaction in an attempt to get new effective anticancer molecules with increased potency (Fig. 3).…”