Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines
A series of ten new hydrazide–hydrazone derivatives bearing a pyrrole ring were synthesized and structurally elucidated through appropriate spectral characteristics. The target hydrazones were assessed for radical scavenging activity through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/9/1198 |
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| author | Diana Tzankova Hristina Kuteva Emilio Mateev Denitsa Stefanova Alime Dzhemadan Yordan Yordanov Alexandrina Mateeva Virginia Tzankova Magdalena Kondeva-Burdina Alexander Zlatkov Maya Georgieva |
| author_facet | Diana Tzankova Hristina Kuteva Emilio Mateev Denitsa Stefanova Alime Dzhemadan Yordan Yordanov Alexandrina Mateeva Virginia Tzankova Magdalena Kondeva-Burdina Alexander Zlatkov Maya Georgieva |
| author_sort | Diana Tzankova |
| collection | DOAJ |
| description | A series of ten new hydrazide–hydrazone derivatives bearing a pyrrole ring were synthesized and structurally elucidated through appropriate spectral characteristics. The target hydrazones were assessed for radical scavenging activity through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests, with ethyl 5-(4-bromophenyl)-1-(2-(2-(4-hydroxy-3,5-dimethoxybenzylidene)hydrazine-yl)-2-oxoethyl)-2-methyl-1H-pyrrole-3-carboxylate (<b>7d</b>) and ethyl 5-(4-bromophenyl)-1-(3-(2-(4-hydroxy-3,5-dimethoxybenzylidene) hydra zine-yl)-3-oxopropyl)-2-methyl-1H-pyrrole-3-carboxylate (<b>8d</b>) highlighted as the best radical scavengers from the series. Additional density functional theory (DFT) studies have indicated that the best radical scavenging ligands in the newly synthesized molecules are stable, do not decompose into elements, are less polarizable, and with a hard nature. The energy of the highest occupied molecular orbital (HOMO) revealed that both compounds possess good electron donation capacities. Overall, <b>7d</b> and <b>8d</b> can readily scavenge free radicals in biological systems via the donation of hydrogen atoms and single electron transfer. The performed in vitro assessment of the compound’s protective activity on the H<sub>2</sub>O<sub>2</sub>-induced oxidative stress model on human neuroblastoma cell line SH-SY5Y determined <b>7d</b> as the most perspective representative with the lowest cellular toxicity and the highest protection. |
| first_indexed | 2024-03-10T22:17:56Z |
| format | Article |
| id | doaj.art-ea4674433cea4832b4457cacc302e0ac |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T22:17:56Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ea4674433cea4832b4457cacc302e0ac2023-11-19T12:23:54ZengMDPI AGPharmaceuticals1424-82472023-08-01169119810.3390/ph16091198Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell LinesDiana Tzankova0Hristina Kuteva1Emilio Mateev2Denitsa Stefanova3Alime Dzhemadan4Yordan Yordanov5Alexandrina Mateeva6Virginia Tzankova7Magdalena Kondeva-Burdina8Alexander Zlatkov9Maya Georgieva10Department “Pharmaceutical Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaLaboratory “Drug metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment “Pharmaceutical Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaLaboratory “Drug metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaLaboratory “Drug metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaLaboratory “Drug metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment “Pharmaceutical Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaLaboratory “Drug metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaLaboratory “Drug metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment “Pharmaceutical Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment “Pharmaceutical Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, BulgariaA series of ten new hydrazide–hydrazone derivatives bearing a pyrrole ring were synthesized and structurally elucidated through appropriate spectral characteristics. The target hydrazones were assessed for radical scavenging activity through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests, with ethyl 5-(4-bromophenyl)-1-(2-(2-(4-hydroxy-3,5-dimethoxybenzylidene)hydrazine-yl)-2-oxoethyl)-2-methyl-1H-pyrrole-3-carboxylate (<b>7d</b>) and ethyl 5-(4-bromophenyl)-1-(3-(2-(4-hydroxy-3,5-dimethoxybenzylidene) hydra zine-yl)-3-oxopropyl)-2-methyl-1H-pyrrole-3-carboxylate (<b>8d</b>) highlighted as the best radical scavengers from the series. Additional density functional theory (DFT) studies have indicated that the best radical scavenging ligands in the newly synthesized molecules are stable, do not decompose into elements, are less polarizable, and with a hard nature. The energy of the highest occupied molecular orbital (HOMO) revealed that both compounds possess good electron donation capacities. Overall, <b>7d</b> and <b>8d</b> can readily scavenge free radicals in biological systems via the donation of hydrogen atoms and single electron transfer. The performed in vitro assessment of the compound’s protective activity on the H<sub>2</sub>O<sub>2</sub>-induced oxidative stress model on human neuroblastoma cell line SH-SY5Y determined <b>7d</b> as the most perspective representative with the lowest cellular toxicity and the highest protection.https://www.mdpi.com/1424-8247/16/9/1198pyrrolesynthesisDFTantioxidantSH-SY5Ycellular toxicity |
| spellingShingle | Diana Tzankova Hristina Kuteva Emilio Mateev Denitsa Stefanova Alime Dzhemadan Yordan Yordanov Alexandrina Mateeva Virginia Tzankova Magdalena Kondeva-Burdina Alexander Zlatkov Maya Georgieva Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines Pharmaceuticals pyrrole synthesis DFT antioxidant SH-SY5Y cellular toxicity |
| title | Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines |
| title_full | Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines |
| title_fullStr | Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines |
| title_full_unstemmed | Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines |
| title_short | Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines |
| title_sort | synthesis dft study and in vitro evaluation of antioxidant properties and cytotoxic and cytoprotective effects of new hydrazones on sh sy5y neuroblastoma cell lines |
| topic | pyrrole synthesis DFT antioxidant SH-SY5Y cellular toxicity |
| url | https://www.mdpi.com/1424-8247/16/9/1198 |
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