CHE-1767: Targeting Neuroinflammation: Novel Triazolo- thiadiazine Hybrids of Deferasirox for Alzheimer's Disease Treatment | [4th International Conference of Sciences “Revamped Scientific Outlook of 21st Century, 2025” , November 12,2025 • 2025]

Author(s):

1. Syed Ahmed Shakir: Dept. of Chemistry, COMSATS Univ. Islamabad, Abbottabad Campus,,Pakistan

2. Umer Rashid: Dept. of Chemistry, COMSATS Univ. Islamabad, Abbottabad Campus,,Pakistan

3. Marryum: Dept. of Chemistry, COMSATS Univ. Islamabad, Abbottabad Campus,,Pakistan

4. Nighat Fatima: Dept. of Pharmacy, COMSATS Univ. Islamabad,Abbottabad Campus,22060,Pakistan

5. Syeda Abida Ejaz: Dept. of Pharma. Chemistry, Faculty of Pharmacy, The Islamia; Univ. of Bahawalpur,Bahawalpur,Pakistan

6. Ammara Fayyaz: Dept. of Pharma. Chemistry, Faculty of Pharmacy, The Islamia; Univ. of Bahawalpur,Bahawalpur,Pakistan

7. Muhammad Zahid Ullah: Dept. of Chemistry, COMSATS Univ. Islamabad, Abbottabad Campus,,Pakistan

8. Aamer Saeed: Dept. of Chemistry,QAU, Islamabad,Pakistan

9. Ajmal Khan: Natural and Med. Sci. Research Center, Univ. of Nizwa,Nizwa,Oman

10. Amara Mumtaz: Dept. of Chemistry, COMSATS Univ. Islamabad, Abbottabad Campus,,Pakistan

Abstract:

It is believed that inflammation influences several physiological processes, including the function of the central nervous system. Moreover, the impairment of lipid mechanisms/pathways is associated with neurodegenerative disorders and onset of Alzheimer's disease (AD). AD is a chronic neurodegenerative disease representing the major cause of dementia worldwide. In this case, the overexpression of different pharmacological targets has been confirmed to address neuronal inflammation and AD, with acetylcholinesterase (AChE), monoamine oxidase-B (MAO-B), cyclooxygenase-2 (COX-2) and 5lipoxygenase (LOX-5) being the most explored targets. Currently, the available treatments are only capable of alleviating the symptoms and not capable of delivering disease-modifying effects. Thus, the current research objective is to synthesize triazolo-thiadiazine derivatives of the deferasirox drug as multi-target compounds that could concurrently inhibit ChEs, MAOs, LOX-5 and COX-2. The synthesized derivatives were confirmed by FTIR, 1H NMR, 13C NMR and DEPT-135 spectroscopic techniques. During in vitro investigations, compound 11 was found to be the most potent inhibitor of all the targeted enzymes. Briefly, this compound exhibited inhibitory values (IC50 ± SEM) of 0.31 ± 0.02, 0.13 ± 0.02 and 0.94 ± 0.11 µM against AChE, MAO-B and COX-2, respectively, suggesting that it is a lead molecule for the synthesis of more potential multitargeted inhibitors. Several compounds, such as compound 9 and 13, showed dual inhibition potential in comparison to standard drugs. Furthermore, molecular docking analysis was performed to validate the in vitro results, where the potent compounds showed some significant interactions with the key amino acids present in the active site of the targeted enzymes. Furthermore, molecular dynamics (MD) simulation data and physicochemical properties supported deferasirox-substituted triazolo- thiadiazine as a promising horizon for the discovery and development of new molecules to treat multifactorial diseases associated with neuro- inflammation, such as AD.

Page(s): 89-89

DOI: DOI not available

Published: Journal: 4th International Conference of Sciences “Revamped Scientific Outlook of 21st Century, 2025” , November 12,2025, Volume: 1, Issue: 1, Year: 2025

Keywords:

Triazole , Cholinesterase inhibitors , triazolthiadiazine , Alzheimer

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