Novel thiazolyl-hydrazone derivatives including piperazine ring: synthesis, in vitro evaluation, and molecular docking as selective MAO-A inhibitor

OSMANİYE D., Alasan R., SAĞLIK B. N., LEVENT S., ÖZKAY Y., KAPLANCIKLI Z. A.

ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES, cilt.77, sa.3-4, ss.167-175, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 77 Sayı: 3-4
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1515/znc-2021-0223
  • Dergi Adı: ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.167-175
  • Anahtar Kelimeler: 2D-NMR, hMAO enzymes, molecular docking, piperazine, thiazolyl-hydrazone, MONOAMINE-OXIDASE B, BIOLOGICAL EVALUATION, DESIGN, SCAFFOLD
  • Anadolu Üniversitesi Adresli: Evet

Özet

MAO-A inhibitors are used in the treatment of depression. There are many studies showing that the thiazolyl-hydrazone structure is a pharmacophore structure for the MAO enzyme. In previous studies by our team, activity studies were carried out with thiazolyl-hydrazone derivatives containing pyrrolidine, morpholine, and piperazine. All of them were displayed MAO-A selective inhibition profile. Additionally, derivatives containing piperazine ring were most active. For this purpose, thiazolyl-hydrazone derivatives containing piperazine were synthesized, but this time an active group, formyl group, was added to the piperazine ring as a substituent. Based on this view, new thiazolyl-hydrazone compounds were synthesized, characterized, and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The structure of the compound was tried to be fully elucidated using 2D NMR technique. The compound including 2,4-dimethyl substituent (3i) were found to be the most effective agents in the series against MAO-A enzyme with the IC50 value of 0.080 +/- 0.003 mu M. The docking study of compound 3i revealed that there is a strong interaction between the active sites of hMAO-A and analyzed compound.