Optimizing adamantane derivatives for enhanced EGFR inhibition in MCF-7 breast cancer cells

被引：0

作者：

Uppar, Pradeep M. ^{[1
]}

Harish, Keshav Kumar ^{[2
]}

Beeraka, Narasimha M. ^{[3
,4
,5
]}

Xi, Zhang ^{[6
]}

Somu, Chaithanya ^{[7
]}

Madegowda, Mahendra ^{[2
]}

Kempasiddegowda, Mamatha Shinduvalli ^{[9
]}

Parameshwaraiah, Sindhu M. ^{[1
]}

Lobie, Peter E. ^{[6
,9
,10
]}

Rangappa, Kanchugarakoppal S. ^{[8
]}

Pandey, Vijay ^{[9
,10
]}

Basappa, Basappa ^{[1
]}

机构：

[1] Univ Mysore, Dept Studies Organ Chem, Lab Chem Biol, Mysore 570006, Karnataka, India

[2] Univ Mysore, Dept Studies Phys, Mysore 570006, Karnataka, India

[3] Sechenov Univ, IM Sechenov First Moscow State Med Univ, Dept Human Anat & Histol, Minist Hlth Russian Federat, 8-2 Trubetskaya Str, Moscow 119991, Russia

[4] Univ Mysore, Dept Studies Mol Biol, Mysore 570006, Karnataka, India

[5] Raghavendra Inst Pharmaceut Educ & Res RIPER, Chiyyedu 515721, Andhra Pradesh, India

[6] Shenzhen Bay Lab, Shenzhen 518055, Peoples R China

[7] Karnataka State Open Univ, Dept Studies & Res Chem, Mysore 570006, Karnataka, India

[8] Univ Mysore, Inst Excellence, Mysuru 570006, Karnataka, India

[9] Tsinghua Univ, Tsinghua Berkeley Shenzhen Inst, Tsinghua Shenzhen Int Grad Sch, Shenzhen 518055, Peoples R China

[10] Tsinghua Univ, Inst Biopharmaceut & Hlth Engn, Tsinghua Shenzhen Int Grad Sch, Shenzhen 518055, Peoples R China

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2025年 / 1331卷

基金：

中国国家自然科学基金;

关键词：

Adamantane; Breast cancer; EGFR; Piperazine; Pyrazoline; ANTICANCER ACTIVITY; VISUALIZATION; DISCOVERY; GROWTH; DESIGN; SYSTEM;

D O I：

10.1016/j.molstruc.2025.141554

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Epidermal growth factor receptor (EGFR) is a key target in breast cancer (BC) treatment due to its significant role in disease progression. This study aims to synthesize novel heterocyclic compounds by tailoring adamantane with pyrazoline followed by piperazines to target EGFR in breast cancer cells. Synthesis of the heterocyclic compounds was performed by Claisen-Schmidt reaction followed by cyclization and concludes with substitution by secondary amines. Structure of the lead compound 1-(3-((3r,5r,7r)-adamantan-1-yl)-5-(4-nitrophenyl)-4,5-dihydro1H-pyrazol-1-yl)-2-(4-(2-nitrophenyl)piperazin-1-yl)ethenone (6c) is confirmed by HRMS, 1H & 13C NMR, IR and Single crystal XRD. In silico docking studies were performed to investigate the molecular interactions of the compound 3, 4 & 6c with the EGFR binding site and to calculate their binding energies. Molecular dynamics simulations were conducted to explore stability of protein-ligand complex for compound 6c within the active site groove of EGFR protein in comparison with its precursors. Additionally, cytotoxic effects of these compounds against MCF-7 breast cancer cells were evaluated using IC-50 assays. Among the synthesized compounds, 6c exhibited significant cytotoxic effects against MCF-7 cells, with IC-50 values of 1.22 mu M. Compound 6c had binding energy of-8.6 kcal/mol, indicating strong interactions within the EGFR binding site indicating their anti- breast cancer potential.

引用

页数：13

共 43 条

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