Design, Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

Abstract

Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940’s. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2‐(2‐bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4‐oxadiazole derivatives 4a–4j have been synthesized and described by spectroscopic method. 2‐(2‐Bromo‐6‐nitrophenyl)‐5‐(4‐bromophenyl)‐1,3,4‐oxadiazole (4c) was reconfirmed by single‐crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF‐7, MDA‐MB‐453 and MCF‐10A non‐cancer cell lines. The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose‐dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein−ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.

RP-HPLC-DAD Method Development and Validation for 1,3,4-Oxadiazole Derivative to Evaluate Its Forced Degradation Behavior and Stability

“…1 Because of its broad range and capacity to target various biological targets, 1,3,4-oxadiazole is a popular scaffold and an exciting pharmacophore for the development of novel drugs. 2,3 As a result, researchers continued to be interested in molecules having this heterocyclic structure. 1,3,4-oxadiazole derivatives, because of their widespread biological and pharmacological activity, are found to be a fascinating compound for the researchers.…”

Biological Evaluation and Molecular Docking Studies of Novel 1,3,4-Oxadiazole Derivatives of 4,6-Dimethyl-2-sulfanylpyridine-3-carboxamide

“…It is a bioisostere for carbonyl-containing derivatives, and is also a valid pharmacophore component, increasing the ability of oxadiazole-containing molecules to bind to a various ligands (e.g., muscarinic receptors, benzodiazepine receptors, dopamine, serotonin and norepinephrine transporters) [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. According to the literature, compounds containing 1,3,4-oxadiazole moiety have confirmed various biological effects, including anticancer [ 42 , 43 ], antimicrobial [ 44 , 45 , 46 , 47 ], antidepressant [ 48 ] and anticonvulsant [ 49 ]. Particularly noteworthy is their analgesic and anti-inflammatory activity [ 50 , 51 ], in many cases associated with the inhibition of cyclooxygenase [ 52 , 53 , 54 ].…”

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

“…The data also show that the adjunction of a [(dialkylamino)alkyl]amino or (hydroxyalkyl)amino side chain enhances anticancer activity of compounds [ 8 , 9 , 10 , 11 ]. There are also studies on novel derivatives with a 3,4-dihydronaphthalen moiety that exhibit anticancer activity [ 12 , 13 ]. Another important chemical group that is present in biologically active agents is hydrazone.…”