Staff View: Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides

Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides

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 spectros...

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Main Authors:	Abdul Qaiyum, Ramle, Nadia Nabihah, Mohd Yusof Chan, Ng, Min Phin, Tan, Chun Hoe, Sim, Kae Shin, Tiekink, Edward R. T. *, Fei, Chee Chin
Format:	Article
Published:	Springer 2023
Subjects:	QD Chemistry QP Physiology RC Internal medicine
Online Access:	http://eprints.sunway.edu.my/2869/ https://link.springer.com/article/10.1007/s11030-023-10662-2
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spelling	my.sunway.eprints.28692024-07-24T07:26:15Z http://eprints.sunway.edu.my/2869/ Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides Abdul Qaiyum, Ramle Nadia Nabihah, Mohd Yusof Chan Ng, Min Phin Tan, Chun Hoe Sim, Kae Shin Tiekink, Edward R. T. * Fei, Chee Chin QD Chemistry QP Physiology RC Internal medicine 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. Springer 2023 Article PeerReviewed 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 https://link.springer.com/article/10.1007/s11030-023-10662-2 10.1007/s11030-023-10662-2
institution	Sunway University
building	Sunway Campus Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Sunway University
content_source	Sunway Institutional Repository
url_provider	http://eprints.sunway.edu.my/
topic	QD Chemistry QP Physiology RC Internal medicine
spellingShingle	QD Chemistry QP Physiology RC Internal medicine Abdul Qaiyum, Ramle Nadia Nabihah, Mohd Yusof Chan Ng, Min Phin Tan, Chun Hoe Sim, Kae Shin Tiekink, Edward R. T. * Fei, Chee Chin Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
description	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.
format	Article
author	Abdul Qaiyum, Ramle Nadia Nabihah, Mohd Yusof Chan Ng, Min Phin Tan, Chun Hoe Sim, Kae Shin Tiekink, Edward R. T. * Fei, Chee Chin
author_facet	Abdul Qaiyum, Ramle Nadia Nabihah, Mohd Yusof Chan Ng, Min Phin Tan, Chun Hoe Sim, Kae Shin Tiekink, Edward R. T. * Fei, Chee Chin
author_sort	Abdul Qaiyum, Ramle
title	Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
title_short	Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
title_full	Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
title_fullStr	Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
title_full_unstemmed	Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
title_sort	structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides
publisher	Springer
publishDate	2023
url	http://eprints.sunway.edu.my/2869/ https://link.springer.com/article/10.1007/s11030-023-10662-2
_version_	1805893825070104576
score	13.211869

Structural insights and cytotoxicity evaluation of benz[e]indole pyrazolyl-substituted amides

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