Schiff bases and their amines: Synthesis and discovery of carbonic anhydrase and acetylcholinesterase enzymes inhibitors

• Published in: Archiv der Pharmazie (Weinheim) Vol. 351; no. 9; pp. e1800146 - n/a
• Main Authors: Yiğit, Beyhan, Yiğit, Murat, Taslimi, Parham, Gök, Yetkin, Gülçin, İlhami
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.09.2018; Wiley Subscription Services, Inc
• Subjects: 1,2‐diaminoethane; 1,3‐diaminopropane; acetylcholinesterase; Acetylcholinesterase - metabolism; Amines - chemical synthesis; Amines - chemistry; Amines - pharmacology; Animals; Butyrylcholinesterase - metabolism; carbonic anhydrase; Carbonic Anhydrase I - antagonists & inhibitors; Carbonic Anhydrase I - isolation & purification; Carbonic Anhydrase I - metabolism; Carbonic Anhydrase II - antagonists & inhibitors; Carbonic Anhydrase II - isolation & purification; Carbonic Anhydrase II - metabolism; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Drug Discovery; Electric Organ; enzyme inhibition; Enzymes; Erythrocytes - enzymology; Horses; Humans; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Schiff bases; Schiff Bases - chemical synthesis; Schiff Bases - chemistry; Schiff Bases - pharmacology; Science & Technology; Structure-Activity Relationship; BIOACTIVITY; Schiff bases; BUTYRYLCHOLINESTERASE; PROFILES; ISOENZYMES I; ANTIBACTERIAL; acetylcholinesterase; enzyme inhibition; ANTIOXIDANT; carbonic anhydrase; 1,2-diaminoethane; ANTIFUNGAL; 1,3-diaminopropane; DERIVATIVES; BROMOPHENOLS; MANNICH-BASES
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201800146

Three series of symmetrical Schiff bases were synthesized from 1,2‐diaminoethane, 1,3‐diaminopropane and 1,4‐diaminobutane and substituted benzaldehydes, and reduced by sodium borohydride to the corresponding benzylic diamines 4–6. All of the compounds obtained were characterized using elemental analysis, FT‐IR, 1H NMR, and 13C NMR spectroscopy. The enzyme inhibitory properties of these compounds were tested and the influence of the alkane chain length and the substituents on the phenyl group on the enzyme inhibition activity were examined. The novel Schiff bases and their amine derivatives (1a–d, 2a–d, 3b–d, 4a–c, 5a–c, 6a, 6c, 6d) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) with Ki values in the range of 159.43 ± 30.03 to 563.73 ± 115.30 nM for hCA I, 104.88 ± 18.44 to 524.32 ± 95.03 nM for hCA II, and 3.95 ± 0.74 to 30.83 ± 6.81 nM for AChE. Three series of symmetrical Schiff bases were synthesized from 1,2‐diaminoethane, 1,3‐diaminopropane and 1,4‐diaminobutane and substituted benzaldehydes and reduced to their corresponding benzylic diamines. The acetylcholinesterase (AChE) and carbonic anhydrase I and II (hCA I and II) inhibitory properties of these compounds were examined, depending on the alkane chain length and the substituents on the phenyl group.