1396397-00-4Relevant academic research and scientific papers
Veratric acid derivatives containing benzylidene-hydrazine moieties as promising tyrosinase inhibitors and free radical scavengers
Dehghani, Zahra,Khoshneviszadeh, Mahsima,Khoshneviszadeh, Mehdi,Ranjbar, Sara
, p. 2644 - 2651 (2019)
Tyrosinase enzyme plays a crucial role in melanin biosynthesis and enzymatic browning process of vegetables and fruits. A series of veratric acid derivatives containing benzylidene-hydrazine moieties with different substitutions were synthesized and their inhibitory effect on mushroom tyrosinase and free radical scavenging activity were evaluated. The results indicated that N′-(4-chlorobenzylidene)-3,4-dimethoxybenzohydrazide (D5)and N′-(2,3-dihydroxybenzylidene)-3,4-dimethoxybenzohydrazide (D12)showed the highest tyrosinase inhibitory activity with IC50 values of 19.72 ± 1.84 and 20.63 ± 0.79 μM, respectively, that were comparable with the IC50 value of kojic acid (19.08 ± 1.21 μM). D12 was also a potent radical scavenger with EC50 value of 0.0097 ± 0.0011 mM. The free radical scavenging activity of D12 was comparable with the standard quercetin. The inhibition kinetic analyzed by Lineweaver-Burk plots revealed that compound D5 was a competitive tyrosinase inhibitor. Molecular docking study was carried out for the derivatives demonstrating tyrosinase inhibitory activity. D5 and D12 possessed the most negative estimated free energies of binding in mushroom tyrosinase active site. Therefore, D5 and D12 could be introduced as potent tyrosinase inhibitors that might be promising leads in medicine, cosmetics and food industry.
Design, synthesis, and pharmacological evaluation of N-acylhydrazones and novel conformationally constrained compounds as selective and potent orally active phosphodiesterase-4 inhibitors
Kümmerle, Arthur E.,Schmitt, Martine,Cardozo, Suzana V. S.,Lugnier, Claire,Villa, Pascal,Lopes, Alexandra B.,Romeiro, Nelilma C.,Justiniano, Hélène,Martins, Marco A.,Fraga, Carlos A. M.,Bourguignon, Jean-Jacques,Barreiro, Eliezer J.
, p. 7525 - 7545 (2012/11/06)
Among a small series of tested N-acylhydrazones (NAHs), the compound 8a was selected as a selective submicromolar phosphodiesterase-4 (PDE4) inhibitor associated with anti-TNF-α properties measured both in vitro and in vivo. The recognition pattern of compound 8a was elucidated through molecular modeling studies based on the knowledge of the 3D-structure of zardaverine, a PDE4 inhibitor resembling the structure of 8a, cocrystallized with the PDE4. Based on further conformational analysis dealing with N-methyl-NAHs, a quinazoline derivative (19) was designed as a conformationally constrained NAH analogue and showed similar in vitro pharmacological profile, compared with 8a. In addition 19 was found active when tested orally in LPS-evoked airway hyperreactivity and fully confirmed the working hypothesis supporting this work.
