Rationally Designed Phenyl- and Phenanthryl-Based Imidazole Hybrids for the Treatment of Breast Cancer—A Structure–Activity Relationship Study
5 affiliations
- 1Dhanvanthri Laboratory, Department of Chemistry, Amrita School of Physical Sciences, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
- 2Center of Excellence in Advanced Materials and Green Technologies (CoE–AMGT), Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641112, India
- 3Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysore 570015, India
- 4Center of Excellence in Cell Biology & Proteomics, College of Pharmaceutical Sciences, School of Health Science, Dayananda Sagar University, Bangalore 562112, India
- 5Institute of Biomolecular Chemistry, CNR, Via Paolo Gaifami 18, 95126 Catania, Italy
Abstract
A series of 11 compounds of phenyl–imidazole–pyrrole and 9 compounds of phenanthryl–imidazole–pyrrole were synthesized and evaluated against breast cancer cell lines differing in the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2, viz., BT-474 (ER+, PR+, and HER2+), T-47D and MCF-7 (ER+, PR+, and HER2−), and MDA-MB-468 and MDA-MB-231 (ER−, PR−, and HER2−). The analysis of the results indicated that the most active compounds were 5d and 5k from the phenyl–imidazole–pyrrole series and 6b and 6i from the phenanthryl–imidazole–pyrrole series (IC50 < 50 µM). Molecular docking (MD) and molecular dynamics simulation (MDS) studies demonstrated that the active compounds exhibited high binding affinity to the 7NH5 (a co-crystal structure of Akt1 and its specific inhibitor) protein, which is overexpressed in many breast cancer types. The active compounds 6b and 6i reduced the viability of MDA-MB-231 and MCF-7 cells by inducing cell death mechanisms. Both compounds halted the proliferation by arresting cells in the G0/G1 phase of the cell cycle. The results are similar to those of traditional Cisplatin. Intraperitoneal administration of 6i retarded the development of EAC tumors and increased the survival of mice compared with tumor-bearing control and 5-fluorouracil (5FU)-treated positive control mice.
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BibTeX
@article{ganesh2026rationally,
title = {{Rationally Designed Phenyl- and Phenanthryl-Based Imidazole Hybrids for the Treatment of Breast Cancer—A Structure–Activity Relationship Study}},
author = {Bharathi Hassan Ganesh and Preethi G. Anantharaju and Amritha Sukumaran and Carmelo Drago and Sarthak Mohanty and Himabindu Padinjarathil and SubbaRao V. Madhunapantula and Prasanna Ramani},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203722},
url = {https://www.mdpi.com/1420-3049/31/20/3722},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Rationally Designed Phenyl- and Phenanthryl-Based Imidazole Hybrids for the Treatment of Breast Cancer—A Structure–Activity Relationship Study
AU - Bharathi Hassan Ganesh
AU - Preethi G. Anantharaju
AU - Amritha Sukumaran
AU - Carmelo Drago
AU - Sarthak Mohanty
AU - Himabindu Padinjarathil
AU - SubbaRao V. Madhunapantula
AU - Prasanna Ramani
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203722
UR - https://www.mdpi.com/1420-3049/31/20/3722
AB - A series of 11 compounds of phenyl–imidazole–pyrrole and 9 compounds of phenanthryl–imidazole–pyrrole were synthesized and evaluated against breast cancer cell lines differing in the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2, viz., BT-474 (ER+, PR+, and HER2+), T-47D and MCF-7 (ER+, PR+, and HER2−), and MDA-MB-468 and MDA-MB-231 (ER−, PR−, and HER2−). The analysis of the results indicated that the most active compounds were 5d and 5k from the phenyl–imidazole–pyrrole series and 6b and 6i from the phenanthryl–imidazole–pyrrole series (IC50 < 50 µM). Molecular docking (MD) and molecular dynamics simulation (MDS) studies demonstrated that the active compounds exhibited high binding affinity to the 7NH5 (a co-crystal structure of Akt1 and its specific inhibitor) protein, which is overexpressed in many breast cancer types. The active compounds 6b and 6i reduced the viability of MDA-MB-231 and MCF-7 cells by inducing cell death mechanisms. Both compounds halted the proliferation by arresting cells in the G0/G1 phase of the cell cycle. The results are similar to those of traditional Cisplatin. Intraperitoneal administration of 6i retarded the development of EAC tumors and increased the survival of mice compared with tumor-bearing control and 5-fluorouracil (5FU)-treated positive control mice.
SN - 1420-3049
ER -