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Synthesis, in vitro cytotoxic and apoptotic effects, and molecular docking study of novel adamantane derivatives.
- Source :
-
Archiv der Pharmazie [Arch Pharm (Weinheim)] 2021 May; Vol. 354 (5), pp. e2000256. Date of Electronic Publication: 2021 Jan 06. - Publication Year :
- 2021
-
Abstract
- [4-(Adamantane-1-carboxamido)-3-oxo-1-thia-4-azaspiro[4.4]nonan-2-yl]acetic acid (4a) and [4-(adamantane-1-carboxamido)-8-nonsubstituted/substituted-3-oxo-1-thia-4-azas-piro[4.5]decane-2-yl]acetic acid (4b-g) derivatives were synthesized; their structures were verified by elemental analysis, infrared spectroscopy, <superscript>1</superscript> H nuclear magnetic resonance (NMR), <superscript>13</superscript> C NMR, and mass spectroscopy data; and their in vitro cytotoxicity activities were investigated against human hepatocellular carcinoma, human prostate adenocarcinoma, and human lung carcinoma cell lines (HepG2, PC-3, and A549, respectively), and a mouse fibroblast cell line (NIH/3T3). All compounds, except compound 4e, were found as cytotoxic, especially on A549 cells as compared with the other cells (selectivity index = 2.01-11.6). As a further step, the effects of compounds 4a-c on apoptosis induction were tested and the expression of selected apoptosis genes was analyzed. Among the selected compounds, compound 4a induced apoptosis remarkably. Moreover, computational calculations of the binding of compounds 4a-c to the BIR3 domain of the human inhibitor of apoptosis protein revealed ligand-protein interactions at the atomistic level and emphasized the importance of a hydrophobic moiety on the ligands for better binding.<br /> (© 2021 Deutsche Pharmazeutische Gesellschaft.)
- Subjects :
- Adamantane analogs & derivatives
Adamantane chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Structure-Activity Relationship
Adamantane pharmacology
Antineoplastic Agents pharmacology
Apoptosis drug effects
Molecular Docking Simulation
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4184
- Volume :
- 354
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Archiv der Pharmazie
- Publication Type :
- Academic Journal
- Accession number :
- 33410150
- Full Text :
- https://doi.org/10.1002/ardp.202000256