Molecular docking analysis of H1 and H2 antihistamines groups with l-asparaginase II for reducing allergenicity; an in silico approach

Massah, Masoumeh; Balmeh, Negar; Goodarzi, Kiomars; Fard, Najaf Allahyari

doi:10.1016/j.imu.2022.100865

Cited by 1 publication

(1 citation statement)

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“…In addition, polyaromatic pyrazoles have important photophysical, optical, and electronic properties [ 5 , 9 ]. Pzs and their derivatives surely play a significant role in medicinal chemistry towards the development of novel and more efficient drugs, considering their active participation in hydrogen bond formation, π-stacking, and dipole–dipole interactions with different biological targets [ 10 ]. Among others, Pzs present significant antibacterial [ 11 ], antimicrobic, anticancer, anti-inflammatory, anti-diabetic, and anti-degenerative activity [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation

Algieri

Algieri²,

Costanzo

et al. 2023

Pharmaceutics

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An efficient, eco-compatible, and very cheap method for the construction of fully substituted pyrazoles (Pzs) via eliminative nitrilimine-alkene 1,3-dipolar cycloaddition (ENAC) reaction was developed in excellent yield and high regioselectivity. Enaminones and nitrilimines generated in situ were selected as dipolarophiles and dipoles, respectively. A deep screening of the employed base, solvent, and temperature was carried out to optimize reaction conditions. Recycling tests of ionic liquid were performed, furnishing efficient performance until six cycles. Finally, a plausible mechanism of cycloaddition was proposed. Then, the effect of three different structures of Pzs was evaluated on the F1FO-ATPase activity and mitochondrial permeability transition pore (mPTP) opening. The Pz derivatives’ titration curves of 6a, 6h, and 6o on the F1FO-ATPase showed a reduced activity of 86%, 35%, and 31%, respectively. Enzyme inhibition analysis depicted an uncompetitive mechanism with the typical formation of the tertiary complex enzyme-substrate-inhibitor (ESI). The dissociation constant of the ESI complex (Ki’) in the presence of the 6a had a lower order of magnitude than other Pzs. The pyrazole core might set the specific mechanism of inhibition with the F1FO-ATPase, whereas specific functional groups of Pzs might modulate the binding affinity. The mPTP opening decreased in Pz-treated mitochondria and the Pzs’ inhibitory effect on the mPTP was concentration-dependent with 6a and 6o. Indeed, the mPTP was more efficiently blocked with 0.1 mM 6a than with 1 mM 6a. On the contrary, 1 mM 6o had stronger desensitization of mPTP formation than 0.1 mM 6o. The F1FO-ATPase is a target of Pzs blocking mPTP formation.

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