Ramle, Abdul Qaiyum and Chan, Nadia Nabihah Mohd Yusof and Ng, Min Phin and Tan, Chun Hoe and Sim, Kae Shin and Tiekink, Edward R. T. and Fei, Chee Chin (2024) Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides. Molecular Diversity, 28 (3). pp. 1363-1376. ISSN 1381-1991, DOI https://doi.org/10.1007/s11030-023-10662-2.
Full text not available from this repository.Abstract
Five new compounds of benze]indole pyrazolyl-substituted amides (2a-e) were synthesised in low to good yields via the direct amide-coupling reaction between a pyrazolyl derivative containing a carboxylic acid and several amine substrates. The molecular structures were determined by various spectroscopic methods, such as NMR (H-1, C-13 and F-19), FT-IR and high-resolution mass spectrometry (HRMS). X-ray crystallographic analysis on the 4-fluorobenzyl derivative (2d) reveals the amide -O atom to reside to the opposite side of the molecule to the pyrazolyl-N and pyrrolyl-N atoms; in the molecular packing, helical chains feature amide-N?H?N(pyrrolyl) hydrogen bonds. Density-functional theory (DFT) at the geometry optimisation B3LYP/6-31G(d) level on the full series shows general agreement with the experimental structures. While the LUMO in each case is spread over the benze]indole pyrazolyl moiety, the HOMO spreads over the halogenated benzosubstituted amide moieties or is localised near the benze]indole pyrazolyl moieties. The MTT assay showed that 2e, exhibited the highest toxicity against a human colorectal carcinoma (HCT 116 cell line) without appreciable toxicity towards the normal human colon fibroblast (CCD-18Co cell line). Based on molecular docking calculations, the probable cytotoxic mechanism of 2e is through the DNA minor groove binding.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Sains Malaysia (304/PKIMIA/6315738), Sunway University Sdn Bhd (GRTIN-RRO-56-2022) |
| Uncontrolled Keywords: | X-ray crystallography; DFT; Cytotoxicity; Minor groove binding |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history |
| Divisions: | Faculty of Science > Institute of Biological Sciences Faculty of Science > Department of Chemistry Deputy Vice Chancellor (Research & Innovation) Office > Nanotechnology & Catalysis Research Centre |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 30 Dec 2024 03:58 |
| Last Modified: | 30 Dec 2024 03:58 |
| URI: | http://eprints.um.edu.my/id/eprint/47168 |
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