Synthesis of novel sulfonamides with anti‐Alzheimer and antioxidant capacities

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Gok N., Akincioglu A., Binici E. E., Akincioglu H., Kilinc N., Goksu S.

Archiv Der Pharmazie, cilt.354, ss.1-12, 2021 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 354
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ardp.202000496
  • Dergi Adı: Archiv Der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1-12
  • Anahtar Kelimeler: acetylcholinesterase, ADME, antioxidant, antiradical, butyrylcholinesterase, molecular docking, phenethylamine, sulfonamide, urea
  • Atatürk Üniversitesi Adresli: Evet

Özet

A series of novel dopamine analogs incorporating urea and sulfonamide functional

groups was synthesized from 3,4‐dimethoxyphenethylamine. The reaction of 3,4‐

dimethoxyphenethylamine with N,N‐dimethylcarbamoyl chloride, followed by the

sulfonyl chlorination of the urea derivative, gave benzene‐1‐sulfonyl chloride 9,

which was reacted with NH3 (aq) or N‐alkyl amines to give related sulfonamides. The

O‐demethylation reaction of the subsequent compounds with BBr3 afforded four

novel phenolic dopamine analogs including sulfonamide and urea in the same

structure. The anticholinergic and antioxidant effects of the synthesized compounds

were examined. Compound 13 exhibited inhibition at the micromolar level for both

acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The IC50 value of 13

was calculated as 298 ± 43 μM for AChE and 321 ± 29 μM for BChE. The antioxidant

and antiradical effects of the molecules were investigated by five different methods.

Among the synthesized compounds 10–18, the best antioxidant and antiradical

activities belong to the phenolic compounds 15–18. Compounds 16 and 18 have a

higher reducing power than the standards used, that is, butylated hydroxytoluene,

butylated hydroxyanisole, Trolox, and α‐tocopherol, for Fe3+–Fe2+ and Cu2+–Cu+

reducing activities. For the DPPH• radical scavenging method, compounds 16–18

have a much better scavenging power than the standard molecules. In addition, it

has been determined by the induced‐fit docking method that compound 13 is wellfitted

in the active site of the enzymes. ADME studies reveal that the pharmacokinetic

and physicochemical properties of all synthesized compounds are within an

acceptable range.