Abdul Qaiyum, Ramle and Nadia Nabihah, Mohd Yusof Chan and Ng, Min Phin and Tan, Chun Hoe and Sim, Kae Shin and Tiekink, Edward R. T. * and Fei, Chee Chin (2023) Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides. Molecular Diversity, 28. ISSN 1573-501X
Full text not available from this repository.Abstract
Five new compounds of benz[e]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 (1H, 13C and 19F), 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 benz[e]indole pyrazolyl moiety, the HOMO spreads over the halogenated benzo-substituted amide moieties or is localised near the benz[e]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 |
|---|---|
| Additional Information: | cytotoxicity; DFT; minor groove binding; X-ray crystallography. |
| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RC Internal medicine |
| Divisions: | Others > Non Sunway Academics Sunway University > School of Engineering and Technology [formerly School of Science and Technology until 2020] > Research Centre for Crystalline Materials moved to SMLS wef 2021 |
| Depositing User: | Ms Yong Yee Chan |
| Date Deposited: | 24 Jul 2024 07:26 |
| Last Modified: | 24 Jul 2024 07:26 |
| URI: | http://eprints.sunway.edu.my/id/eprint/2869 |
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