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Updated: Jun 7, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
New thiophene derivatives: chemoselective synthesis, antitumor effectiveness, structural characterization, DFT
Abdullatif Bin Muhsinah1, Mohammed M Alharbi2, Nabila A Kheder3
1Department of Pharmacognosy, College of Pharmacy, King Khalid University, P.O. Box 960, Abha, 61421, Saudi Arabia.
Abstract:
In this study, the chemoselective synthesis of two new thiophene derivatives is presented. The structure of newly synthesized thiophenes derivatives; ethyl 4-acetyl-3-phenyl-5-(phenylamino)thiophene-2-carboxylate (5) and ethyl (E)-4-(3-(dimethylamino)acryloyl)-3-phenyl-5-(phenylamino)thiophene-2-carboxylate (8) were established using different FTIR and NMR spectral analyses. Compound 8 was isolated as single crystal and its 3D structure was determined using X-ray crystallographic analysis. Possible intermolecular interactions that control the molecular packing of 8 were elucidated using Hirshfeld topology analysis. The O…H (13.7%), H…H (55.3%) and C…C (2.3%) intermolecular interactions are the most significant. Fukui functions showed that C4 in thiophene 5 and C3 in thiophene 8 are the most reactive atoms for nucleophilic attack, while N9 in thiophene 5 and C1 in thiophene 8 are the most reactive atoms for electrophilic attack. Antitumor activity of thiophene 5 was assessed and the results showed higher activity against HepG-2 (7.46 µg/mL) compared to the HCT 116 (12.60 µg/mL) cell line.
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