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| Format: | Recurso digital |
| Language: | English |
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2023
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| Online Access: | https://doi.org/10.1155/2023/8992853 |
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| _version_ | 1866901924647796736 |
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| author | Al-Khayat, Mohammad Ammar Jabbour, Mirna Al-Ktaifani, Mahmoud |
| author_facet | Al-Khayat, Mohammad Ammar Jabbour, Mirna Al-Ktaifani, Mahmoud |
| contents | <p>Purpose. To synthesize new isoindole-1,3(2H)-dione derivatives by molecular hybridization of gabapentin and pregabalin with<br>phthalic anhydride derivatives and to evaluate their biological activity as promising antioxidant, antimicrobial, and anticancer<br>agents. Method. Molecular hybridization was successfully achieved by two procedures; synthesized compounds were characterized<br>using analytical and spectral methods. ,e free radical scavenging properties of synthesized compounds were evaluated using the<br>DPPH method. ,e antibacterial activity of synthesized compounds and parent compounds was evaluated against two microbial<br>Gram-positive and Gram-negative strains by the well di<usion method. Furthermore, we have studied the e<ect of compounds on<br>proliferation, cell cycle, and cell death in two human cancer cell lines (Caco-2 and HCT-116). Results. Compounds 1, 3, and 4<br>exhibited a good free radical scavenging e<ect, and compound 3 is the most e<ective with IC50 value of 2.525 *mol/mL. All<br>compounds showed antibacterial activity against Escherichia coli and Staphylococcus aureus related to concentration, while parent<br>drugs did not exhibit any antibacterial e<ect. Compounds 1 and 2 showed a good zone of inhibition against E. coli at micromolar<br>concentrations, and they are more e<ective than Gentamicin Sulfate. Treatment with the studied compounds suppresses<br>proliferation, arrests progress throughout the cell cycle, and induces apoptosis in Caco-2 and HCT-116 cancer cells. Compound 2<br>is highly e<ective against Caco-2 cells and more e<ective than thalidomide, with IC50 value less than 1 *mol/L. Conclusion. Our<br>results showed that molecular hybridization of gabapentin and pregabalin in the isoindole-1,3(2H)-dione moiety results in<br>promising anticancer and antimicrobial molecules. Results of this preliminary study show that halogenation of the isoindole-<br>1,3(2H)-dione moiety improves antimicrobial and anticancer activity and that tetra-brominated derivatives are comparable to or<br>more e<ective than related tetra-chlorinated derivatives.<br>1. Introduction<br>Research for new, safe, and e<ective drugs has been a continuous<br>need over the years, especially since there are still<br>challenging diseases with no su@cient treatments, such as<br>cancer, neurodegenerative diseases, autoimmune diseases,<br>and infectious diseases related to resistant microorganisms.<br>,erapeutic choices for complex, heterogeneous diseases<br>can be</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_1155_2023_8992853 |
| institution | Zenodo |
| language | eng |
| publishDate | 2023 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3(2H)-Dione Moiety as Potential Antioxidant, Antimicrobial, and Anticancer Agents Al-Khayat, Mohammad Ammar Jabbour, Mirna Al-Ktaifani, Mahmoud <p>Purpose. To synthesize new isoindole-1,3(2H)-dione derivatives by molecular hybridization of gabapentin and pregabalin with<br>phthalic anhydride derivatives and to evaluate their biological activity as promising antioxidant, antimicrobial, and anticancer<br>agents. Method. Molecular hybridization was successfully achieved by two procedures; synthesized compounds were characterized<br>using analytical and spectral methods. ,e free radical scavenging properties of synthesized compounds were evaluated using the<br>DPPH method. ,e antibacterial activity of synthesized compounds and parent compounds was evaluated against two microbial<br>Gram-positive and Gram-negative strains by the well di<usion method. Furthermore, we have studied the e<ect of compounds on<br>proliferation, cell cycle, and cell death in two human cancer cell lines (Caco-2 and HCT-116). Results. Compounds 1, 3, and 4<br>exhibited a good free radical scavenging e<ect, and compound 3 is the most e<ective with IC50 value of 2.525 *mol/mL. All<br>compounds showed antibacterial activity against Escherichia coli and Staphylococcus aureus related to concentration, while parent<br>drugs did not exhibit any antibacterial e<ect. Compounds 1 and 2 showed a good zone of inhibition against E. coli at micromolar<br>concentrations, and they are more e<ective than Gentamicin Sulfate. Treatment with the studied compounds suppresses<br>proliferation, arrests progress throughout the cell cycle, and induces apoptosis in Caco-2 and HCT-116 cancer cells. Compound 2<br>is highly e<ective against Caco-2 cells and more e<ective than thalidomide, with IC50 value less than 1 *mol/L. Conclusion. Our<br>results showed that molecular hybridization of gabapentin and pregabalin in the isoindole-1,3(2H)-dione moiety results in<br>promising anticancer and antimicrobial molecules. Results of this preliminary study show that halogenation of the isoindole-<br>1,3(2H)-dione moiety improves antimicrobial and anticancer activity and that tetra-brominated derivatives are comparable to or<br>more e<ective than related tetra-chlorinated derivatives.<br>1. Introduction<br>Research for new, safe, and e<ective drugs has been a continuous<br>need over the years, especially since there are still<br>challenging diseases with no su@cient treatments, such as<br>cancer, neurodegenerative diseases, autoimmune diseases,<br>and infectious diseases related to resistant microorganisms.<br>,erapeutic choices for complex, heterogeneous diseases<br>can be</p> |
| title | Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3(2H)-Dione Moiety as Potential Antioxidant, Antimicrobial, and Anticancer Agents |
| url | https://doi.org/10.1155/2023/8992853 |