Inhibition of monoamine oxidase–A activity in rat brain by synthetic hydrazines: Structure-activity relationship (SAR)

Abstract

A series of hydrazine derivatives was synthesized in order to evaluate their monoamine oxidase A (MAO-A) inhibitory effects. MAO-A inhibitory activity of 4-tosyl benzoic acid carbohydrazide was quite potent, similarly to that of the corresponding 4-benzyloxy-benzoic acid carbohydrazide and its N-cyanoethylated derivative. Structural variations of these compounds, such as the replacement of the 4-substitutent, of the aromatic ring on which the carbohydrazide moiety is grafted, as well as cyclization of the hydrazide moiety in five- or six-membered rings caused either significant decline or complete loss of MAO inhibitory properties. The most active compound (4-tosyl benzoic acid carbohydrazide) was also subjected to the forced swim test, an animal model of depression, eliciting a marked reduction in immobility time in rats, without affecting the locomotor activity, implying that it possesses anti-depressant properties due to inhibition of MAO type-A.

Total monoamine oxidase (MAO) inhibition by chestnut honey, pollen and propolis

“…Previous studies to date have assessed the antioxidant, antimicrobial, antiinflammatory, anti-carcinogenic and carbonic anhydrase (CA) inhibitory effects and the hepatoprotective role of the bee products 2,[7][8][9][10][11][12][13][14][15][16] . Similarly, MAO is inhibited by some plant extracts with a high content of phenolic compounds [17][18][19] and some synthetic hydrazines 20 . There are information gaps on MAO inhibition by bee products, however, which this study is intended to help fill.…”

Parkinson's Disease Management. Part II- Discovery of MAO-B Inhibitors Based on Nitrogen Heterocycles and Analogues

“…The nucleus was identified as a promising pharmacophore to be modulated for the design and development of potent and selective hMAO-B inhibitors [73,81,82], and the mechanism of action was thoroughly investigated [83][84][85]. The data obtained allow to conclude that the nature of the substituent on the phenyl ring (R 2; structure on Table 3) largely modulates the activity, as shown by the introduction of several groups in ortho and para positions ( Table 3).…”

Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity

“…However, they were withdrawn due to their toxic side effects . Subsequently, different families of heterocycles containing 2 or 4 nitrogen atoms were used as scaffolds for synthesizing reversible and selective MAO inhibitors . 2‐Pyrazolines, which form one of these families, can also be considered as a cyclic hydrazine derivative.…”

“…16 Subsequently, different families of heterocycles containing 2 or 4 nitrogen atoms were used as scaffolds for synthesizing reversible and selective MAO inhibitors. [17][18][19][20][21][22][23] 2-Pyrazolines, which form one of these families, can also be considered as a cyclic hydrazine derivative. On the basis of the clinical profiles of hydrazine and other heterocycles, researchers focused on structural modifications of the pyrazoline to enhance the pharmacological activity.…”