Synthesis of N '-(4-/3-/2-/Non-substituted benzylidene)-4-[(4-methylphenyl)sulfonyloxy] Benzohydrazides and Evaluation of Their Inhibitory Activities against Monoamine Oxidases and beta-Secretase

SELLİTEPE H. E., Oh J. M., DOĞAN İ. S., YILDIRIM S., AKSEL A. B., Jeong G. S., ...Daha Fazla

APPLIED SCIENCES-BASEL, cilt.11, sa.13, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11 Sayı: 13
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3390/app11135830
  • Dergi Adı: APPLIED SCIENCES-BASEL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Agricultural & Environmental Science Database, Applied Science & Technology Source, Communication Abstracts, INSPEC, Metadex, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: tosylated acyl hydrazide derivatives, monoamine oxidases, cholinesterases, beta-secretase, structure-activity relationship, inhibitory activity, molecular docking, HYDRAZONES, DERIVATIVES, BUTYRYLCHOLINESTERASE, ACETYLCHOLINESTERASE, AGENTS
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Nineteen tosylated acyl hydrazone derivatives were synthesized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase (BACE-1) were evaluated. Compound 3o was the most potent inhibitor of MAO-A, with an IC50 value of 1.54 mu M, followed by 3a (IC50 = 3.35 mu M). A structural comparison with 3a indicated that the 3-F group in 3o increased its inhibitory activity against MAO-A. Compound 3s was the most potent inhibitor of MAO-B, with an IC50 value of 3.64 mu M, followed by 3t (IC50 = 5.69 mu M). The MAO-B inhibitory activity increased in the order of 3- > 4- > 2-NO2 groups in 3s, 3t, and 3r, respectively. All the compounds weakly inhibited AChE and BChE, which retained >50% residual activity at 10 mu M, except for 3a, which inhibited BChE with an IC50 value of 16.1 mu M. Interestingly, 3e, 3f, and 3n inhibited BACE-1 with IC50 values of 8.63, 9.92, and 8.47 mu M, respectively, which were lower than the IC50 of the quercetin reference. Compounds 3o and 3s were found to be reversible competitive inhibitors of MAO-A and MAO-B, respectively, with K-i values of 0.35 +/- 0.074 and 1.97 +/- 0.65 mu M, respectively. Moreover, compounds 3e, 3f, and 3n were effective BACE-1 inhibitors. The lead molecules were further investigated by molecular docking studies to elucidate the binding interactions with the target enzymes.