A versatile synthetic approach to various 5-alkynyl modified isatin derivatives: Cytotoxicity, acetylcholinesterase inhibition activity and molecular modeling study
| Parent link: | Bioorganic Chemistry.— .— Amsterdam: Elsevier Science Publishing Company Inc. Vol. 165.— 2025.— Article number 109038, 17 p. |
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| Other Authors: | , , , , , , , |
| Summary: | Title screen Isatin derivatives have been of great interest in drug development research. 5-Alkynyl substituted isatin derivatives with anticancer potential and acetylcholinesterase inhibition (AChE) activity are designed and synthesized. The copper(I) catalyzed one-pot three-component reaction (AChauhan et al. (2021)3-coupling) of new 3-(1,3-dioxolane)-5-(ethynyl)isatins with formaldehyde and secondary amines or the Sonogashira cross-coupling reaction of C-3 protected iodoisatins with fluoro-N-(prop-2-ynyl)benzamide and prop-2-ynyl 4-fluorobenzoate were the main approaches for the synthesis of 5-(3-X-prop-1-yn-1-yl) substituted isatin derivatives (yield 53–87 %). 1-Benzyl-5-(prop-1-yn-1-yl)indoline-2,3-diones are smoothly formed by refluxing of 3-(1,3-dioxolane)-5-(propynyl)isatins in hydrochloric acid/MeOH (1:9, v/v). Results of in vitro biological assays (MTT-test) revealed that new 3-(1,3-dioxolane)-5-(3-X-prop-1-yn-1-yl)-1-benzylisatin derivatives are exhibited remarkable cytotoxicity against human cervical (C 33 A and CaSki), breast (MCF-7), prostate (DU-145) and glioblastoma (SNB-19 and T98G) cancer cell lines within low micromolar GI50 values. Additionally, all new compounds demonstrated relatively low cytotoxicity against the normal epithelial VERO cells (GI50 > 70 μM), indicating good selectivity. Moreover, the appropriate isatin derivatives displayed good and moderate acetylcholinesterase inhibition activity in vitro (Ellman’ s method) with IC50 up to 1.0–3.7 μM comparable to that for clinically used galantamine. Based on the results of in silico experiments the isatin derivatives bearing 5-(prop-1-yn-1-yl) substituents are promising for further search of acetylcholinesterase inhibitors in this series of compounds Текстовый файл AM_Agreement |
| Language: | English |
| Published: |
2025
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| Subjects: | |
| Online Access: | https://doi.org/10.1016/j.bioorg.2025.109038 |
| Format: | Electronic Book Chapter |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=684408 |
| Summary: | Title screen Isatin derivatives have been of great interest in drug development research. 5-Alkynyl substituted isatin derivatives with anticancer potential and acetylcholinesterase inhibition (AChE) activity are designed and synthesized. The copper(I) catalyzed one-pot three-component reaction (AChauhan et al. (2021)3-coupling) of new 3-(1,3-dioxolane)-5-(ethynyl)isatins with formaldehyde and secondary amines or the Sonogashira cross-coupling reaction of C-3 protected iodoisatins with fluoro-N-(prop-2-ynyl)benzamide and prop-2-ynyl 4-fluorobenzoate were the main approaches for the synthesis of 5-(3-X-prop-1-yn-1-yl) substituted isatin derivatives (yield 53–87 %). 1-Benzyl-5-(prop-1-yn-1-yl)indoline-2,3-diones are smoothly formed by refluxing of 3-(1,3-dioxolane)-5-(propynyl)isatins in hydrochloric acid/MeOH (1:9, v/v). Results of in vitro biological assays (MTT-test) revealed that new 3-(1,3-dioxolane)-5-(3-X-prop-1-yn-1-yl)-1-benzylisatin derivatives are exhibited remarkable cytotoxicity against human cervical (C 33 A and CaSki), breast (MCF-7), prostate (DU-145) and glioblastoma (SNB-19 and T98G) cancer cell lines within low micromolar GI50 values. Additionally, all new compounds demonstrated relatively low cytotoxicity against the normal epithelial VERO cells (GI50 > 70 μM), indicating good selectivity. Moreover, the appropriate isatin derivatives displayed good and moderate acetylcholinesterase inhibition activity in vitro (Ellman’ s method) with IC50 up to 1.0–3.7 μM comparable to that for clinically used galantamine. Based on the results of in silico experiments the isatin derivatives bearing 5-(prop-1-yn-1-yl) substituents are promising for further search of acetylcholinesterase inhibitors in this series of compounds Текстовый файл AM_Agreement |
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| DOI: | 10.1016/j.bioorg.2025.109038 |