Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials
Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All fina...
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2024-04-01
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| Series: | Pharmaceutical Sciences |
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| Online Access: | https://ps.tbzmed.ac.ir/PDF/ps-30-143.pdf |
| _version_ | 1797209877792161792 |
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| author | Young Ho Lee Gwan Gyu Song |
| author_facet | Young Ho Lee Gwan Gyu Song |
| author_sort | Young Ho Lee |
| collection | DOAJ |
| description | Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride:urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration. Results: The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing. Conclusion: Tocilizumab may be the most efficient remission-inducing and relapse-lowering biological agent for patients with GCA, and TNF inhibitors pose the highest risk of infection among the biologics studied. |
| first_indexed | 2024-04-24T10:01:41Z |
| format | Article |
| id | doaj.art-23627bff382e4d719feab9a947ba678c |
| institution | Directory Open Access Journal |
| issn | 2383-2886 |
| language | English |
| last_indexed | 2024-04-24T10:01:41Z |
| publishDate | 2024-04-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Pharmaceutical Sciences |
| spelling | doaj.art-23627bff382e4d719feab9a947ba678c2024-04-13T10:35:01ZengTabriz University of Medical SciencesPharmaceutical Sciences2383-28862024-04-0130214315210.34172/PS.2023.26ps-39906Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled TrialsYoung Ho Lee0Gwan Gyu Song1Department of Rheumatology, Korea University Medicine, Seoul, Korea.Department of Rheumatology, Korea University Medicine, Seoul, Korea.Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride:urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration. Results: The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing. Conclusion: Tocilizumab may be the most efficient remission-inducing and relapse-lowering biological agent for patients with GCA, and TNF inhibitors pose the highest risk of infection among the biologics studied.https://ps.tbzmed.ac.ir/PDF/ps-30-143.pdfbiologic agentsgiant cell arteritisnetwork meta-analysistocilizumab |
| spellingShingle | Young Ho Lee Gwan Gyu Song Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials Pharmaceutical Sciences biologic agents giant cell arteritis network meta-analysis tocilizumab |
| title | Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials |
| title_full | Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials |
| title_fullStr | Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials |
| title_full_unstemmed | Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials |
| title_short | Comparative Effectiveness and Safety of Biologic Treatments in Giant Cell Arteritis: A Network Meta-analysis of Randomized Controlled Trials |
| title_sort | comparative effectiveness and safety of biologic treatments in giant cell arteritis a network meta analysis of randomized controlled trials |
| topic | biologic agents giant cell arteritis network meta-analysis tocilizumab |
| url | https://ps.tbzmed.ac.ir/PDF/ps-30-143.pdf |
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