DESIGN, SYNTHESIS, CHARACTERIZATION, BIOACTIVITY AND MOLECULAR DOCKING STUDIES OF NOVEL SULFAMIDES


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Naderi A., Akincioglu A., Cagan A., GÖKSU S., Taslimi P., GÜLÇİN İ.

STUDIA UNIVERSITATIS BABES-BOLYAI CHEMIA, cilt.68, sa.2, ss.145-168, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 68 Sayı: 2
  • Basım Tarihi: 2023
  • Doi Numarası: 10.24193/subbchem.2023.2.10
  • Dergi Adı: STUDIA UNIVERSITATIS BABES-BOLYAI CHEMIA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, Central & Eastern European Academic Source (CEEAS)
  • Sayfa Sayıları: ss.145-168
  • Anahtar Kelimeler: Synthesis, 3-phenylbutylamine, sulfamide, biological effects, molecular docking, ANHYDRASE INHIBITORY PROPERTIES, CARBONIC-ANHYDRASE, ACETYLCHOLINESTERASE, DERIVATIVES, POTENT, BUTYRYLCHOLINESTERASE, PROFILES, CRYSTAL
  • Atatürk Üniversitesi Adresli: Evet

Özet

Starting from commercially available 4-phenylbutanoic acids, a series of novel sulfamides were synthesized and investigated for their inhibition properties on the human carbonic anhydrase I and II (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. SAR was also evaluated with molecular docking study. These new compounds were tested against hCA I and hCA II, BChE, and AChE. The majority of the synthetic compounds were more effective against AChE than tacrine, a common inhibitor. Additionally, tacrine was not the only synthetic substance that was more effective against BChE. The obtained results revealed that N,N-dimethyl-[3-(2,4-dimethoxyphenyl)propyl]sulfamide 25, with Ki of 94.22 & PLUSMN;42.37 nM against AChE and Ki of 230.91 & PLUSMN;46.22 nM against BChE, was the most potent compound against cholinesterase enzymes. These recently created substances were tested for their ability to inhibit hCA I and II isoforms. In comparison to the conventional inhibitor acetazolamide, the majority of produced sulfamide derivatives 25-29 also inhibited these investigated isoforms. In particular, sulfamide derivatives 25-29 with substituents N,N-dimethyl-[3-(3,5-dimethoxyphenyl)propyl]sulfamide 26 and N,N-dimethyl-[3-(3,4-dimethoxyphenyl)propyl]sulfamide 27 emerged as the most potent hCA inhibitors.