Published January 1, 2024 | Version v1
Journal article Open

Exploring Benzo[<i>b</i>][1,4]Thiazine Derivatives: Multitarget Inhibition, Structure-Activity Relationship, Molecular Docking, and ADMET Analysis

  • 1. Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan
  • 2. Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan
  • 3. Imam Abdulrahman Bin Faisal Univ, Inst Res & Med Consultat IRMC, Dept Clin Pharm Res, Dammam 31441, Saudi Arabia
  • 4. Bartin Univ, Fac Sci, Dept Biotechnol, TR-74100 Bartin, Turkiye
  • 5. Sivas Cumhuriyet Univ, Tech Sci Vocat Sch Sivas, Plant & Anim Prod Dept, TR-58140 Sivas, Turkiye
  • 6. Kastamonu Univ, Fac Engn & Architecture, Dept Genet & Bioengn, TR-37150 Kastamonu, Turkiye
  • 7. Biruni Univ, Sch Med, Med Biochem Dept, TR-34010 Istanbul, Turkiye

Description

A series of benzothiazine derivatives (1-17) were synthesized via an intermolecular cyclo condensation reaction involving 2-aminothiophenol (i) and substituted phenacyl bromide (ii). Structural elucidation of these synthetic derivatives utilized EI-MS, HR-EIMS, H-1 NMR, and C-13 NMR spectroscopic techniques. The synthesized analogs were evaluated against key enzyme targets (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glucosidase (alpha-Glu)) and tested for cytotoxicity against various cancer cell lines. Six compounds were selected based on their inhibition profiles, exhibiting significant inhibitory potential against enzymes. In silico studies corroborated the observed inhibitory activities, aligning closely with experimental outcomes. Additionally, an ADME/T study provided insights into pharmacokinetic and safety profiles, identifying promising candidates for future drug development efforts.

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