Synthesis, single-crystal X-ray diffraction (SC-XRD), density functional theory (DFT), Hirshfeld surface analysis, dihydrofolate reductase inhibition, pharmacokinetic evaluation, and molecular docking studies of 9,9-dibutylfluorene-2-carboxylic acid
Journal of the Iranian Chemical Society, vol.23, no.6, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 23 Issue: 6
- Publication Date: 2026
- Doi Number: 10.1007/s13738-026-03407-z
- Journal Name: Journal of the Iranian Chemical Society
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Keywords: DFT, Dihydrofolate reductase, Hirshfeld surface analysis, Molecular docking, Pharmacokinetic studies, SC-XRD
- Hacettepe University Affiliated: Yes
Abstract
The current study explores the synthesis, structural characterization, and pharmacological assessment of 9,9-dibutylfluorene-2-carboxylic acid, focusing on its potential as an inhibitor of dihydrofolate reductase (DHFR), a crucial enzyme in cancer treatment. SC-XRD confirmed its molecular structure, detailing essential bond lengths and angles, while Hirshfeld surface analysis identified significant intermolecular interactions primarily driven by H-bonding and van der Waals forces. Density Functional Theory (DFT) revealed stable electronic properties, providing deeper insight into the optimized geometric parameters. Molecular docking established a strong binding affinity to DHFR, indicating promising inhibitory effects. Furthermore, pharmacokinetic analysis suggested favorable drug-like properties, including high gastrointestinal absorption. Together, the findings present this compound as a fascinating candidate for future development as a fluorene-based anticancer agent.