Academic Journal
Design, synthesis, in silico, and in vitro evaluation of novel benzyloxybenzene substituted (S)‐α‐amino amide derivatives as cholinesterases and monoaminoxidases inhibitor.
| العنوان: | Design, synthesis, in silico, and in vitro evaluation of novel benzyloxybenzene substituted (S)‐α‐amino amide derivatives as cholinesterases and monoaminoxidases inhibitor. |
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| المؤلفون: | Akıncıoğlu, Akın1,2 (AUTHOR) akinakincioglu@gmail.com |
| المصدر: | Drug Development Research. Apr2024, Vol. 85 Issue 2, p1-16. 16p. |
| مصطلحات موضوعية: | *AMIDE derivatives, *CHOLINESTERASES, *MONOAMINE oxidase, *METHYL formate, *BENZYL bromide, *ESTER derivatives |
| مستخلص: | In this study, a series of novel benzyloxybenzene substituted (S)‐α‐amino acid methyl esters and their amide derivatives were synthesized and evaluated for their inhibitory actions against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase A (MAO‐A), and monoamine oxidase B (MAO‐B). The synthetic strategy was based on starting from benzyl bromide (5) and 4‐hydroxybenzaldehyde (6). The reaction of 5 and 6 in the presence of K2CO3 gave benzyloxybenzaldehyde 7. Benzyloxybenzene substituted (S)‐α‐amino acid methyl esters 11, 12, 13, (±)‐19, and (±)‐20 were obtained from the reaction of L‐amino acid methyl esters with benzyloxybenzaldehyde (7) followed by in situ reduction with NaBH4. The reaction of (S)‐11, (S)‐12, 13, (±)‐19, and (±)‐20 with excess ammonia gave amides (S)‐14, (S)‐15, 16, (±)‐21, and (±)‐22. The in vitro inhibitory activities of compounds against MAO‐A, MAO‐B, AChE, and BChE were investigated. Within the α‐amino acid methyl ester series, 13 (21.32 ± 0.338 µM) showed selectivity by inhibiting the MAO‐B better than MAO‐A. 13 emerged as the most active member of this series, exhibiting a 12‐fold selectivity for MAO‐B. 14 (4.501 ± 0.295 µM) demonstrated a pronounced selectivity for MAO‐A over MAO‐B, with a selectivity ratio of 110‐fold. In addition, it was determined that compound 15 (95.65 ± 3.09 µM) had high selectivity for BChE inhibition. 21 was demonstrated the most potent inhibition (18.36 ± 1.36 µM) against AChE. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: | Academic Search Index |
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