In Silico Design, Synthesis and Bioactivity of N-(2, 4-Dinitrophenyl)-3-oxo- 3-phenyl-N-(aryl) Phenyl Propanamide
Mucheli Ramana1, Rama Lokhande2, Shanta Bhar3
1Department of Chemistry, University of Mumbai, Santacruz (East), Mumbai-400098, India.
Background:
Breast cancer is a systemic disease which has challenged physicians worldwide as it is the most predominant cancer in women often leading to fatality. One of the types of treatment is chemotherapy which includes targeted oral or intravenous cancer-killing drugs. Treatment options are often limited to surgery and/or chemotherapy.
Objective:
The discovery and design of new small molecule estrogen inhibitors is necessitated in order to circumvent the problem of drug-induced resistance in chemotherapy resulting in disease relapse. Chemoinformatics facilitates the design, selection and synthesis of new drug candidates for breast cancer by providing efficient in silico techniques for prediction of favourable ADMET properties, and structural descriptors to profile druggability of a compound.
Method:
Several molecules selected from docking studies were synthesized and evaluated for their biological activities on the MCF-7 (human breast cancer) cell line.
Results:
These estrogen inhibitors displayed good inhibitory activity with high selectivity and hence can be further progressed as drug candidates effective against breast cancer.
Conclusion:
It is for the first time that N-(2, 4-dinitrophenyl)-3-oxo-3-phenyl-N-(aryl) phenylpropanamide derivatives were reported to be biological active as potential breast cancer inhibitors.
Insights
New N-(2, 4-dinitrophenyl)-3-oxo-3-phenyl-N-(aryl) phenylpropanamide derivatives show promise as breast cancer inhibitors. These compounds exhibit significant biological activity and selectivity, offering potential new avenues for chemotherapy drug development.
Area of Science:
- Medicinal Chemistry
- Drug Discovery
- Computational Chemistry
Background:
- Breast cancer is a leading cause of cancer-related mortality in women globally.
- Current treatment options like chemotherapy face challenges due to drug resistance and disease relapse.
- Development of novel small molecule estrogen inhibitors is crucial to overcome resistance.
Purpose of the Study:
- To design and synthesize novel small molecule estrogen inhibitors for breast cancer treatment.
- To utilize chemoinformatics for predicting favorable ADMET properties and druggability.
- To identify potential drug candidates effective against breast cancer.
Main Methods:
- In silico docking studies were performed to select promising molecules.
- Selected molecules were synthesized.
- Biological activities were evaluated on the MCF-7 human breast cancer cell line.
Main Results:
- The synthesized estrogen inhibitors demonstrated significant inhibitory activity against breast cancer cells.
- High selectivity was observed for these compounds.
- The compounds showed potential for further development as breast cancer drug candidates.
Conclusions:
- N-(2, 4-dinitrophenyl)-3-oxo-3-phenyl-N-(aryl) phenylpropanamide derivatives were identified as novel biologically active compounds.
- These derivatives represent a new class of potential breast cancer inhibitors.
- The study highlights the potential of these compounds for future therapeutic applications.
