Molecular Modelling Studies of Pyridazinone Derivatives as Antibutyrylcholinesterases
Mehmet Abdullah Alagoz,
Zeynep Ozdemir,
Azime Berna Ozcelik
Issue:
Volume 5, Issue 3, May 2019
Pages:
26-30
Received:
30 July 2019
Accepted:
26 August 2019
Published:
16 September 2019
Abstract: Background: Butyrylcholinesterase (BChE) is known serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Although the role of the other serine hydrolase enzyme, acetylcholinesterase (AChE) in cholinergic transmission is well known, the role of BChE has not been elucidated sufficiently. The hydrolysis of acetylcholine in the synaptic healthy brain cells mainly carried out by AChE, it is accepted that contribution to the hydrolysis of BChE is very low; but both AChE and BChE are known to play an active role in neuronal development and cholinergic transmission. Docking is a method that predicts the preferential orientation of a molecule (small molecule) to a second (protein) molecule when connected to form a stable complex. It is used to predict the affinity of small molecule drug candidates against protein targets, their binding to these proteins, and hence their biological activity. Objective: In this study, we examined a series of pyridazinone-derived compounds, previously synthesized by our research group, for the compatibility of BChE enzyme and some physicochemical properties of the compounds in silico. Method: The compounds were optimized by conjugated gradient method by creating three dimensional models with OPLS_2005 force field parameters with 2D Sketcher and MacroModel (Schrödinger, LLC, NY) software in Maestro (Schrödinger, LLC, NY). Results: When the activities of the compounds were compared with the physicochemical parameters calculated by computerized methods, some parameters were found to be directly related to the activity. Conclusion: This study supports that the researchers may use to calculate various physicochemical properties and to make molecular modeling studies before working with pyridazinone derivates.
Abstract: Background: Butyrylcholinesterase (BChE) is known serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Although the role of the other serine hydrolase enzyme, acetylcholinesterase (AChE) in cholinergic transmission is well known, the role of BChE has not been elucidated sufficiently. The hydrolysis of acetylcholine in the...
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A Review on the Properties and Uses of Paracetamol
Issue:
Volume 5, Issue 3, May 2019
Pages:
31-35
Received:
13 August 2019
Accepted:
6 September 2019
Published:
21 September 2019
Abstract: N-acylated aromatic amines (those having an acyl group, RCO- substituted on nitrogen) are important in over-the-counter headache remedies. Over-the-counter drugs are those you may buy without a prescription. Paracetamol is virtually the sole survivor of the so-called “aniline derivatives” or “aniline analgesics” which are; acetanilide, phenacetin and paracetamol (acetaminophen). Phenacetin and paracetamol are both derivatives of acetanilide. Paracetamol which is also referred to as 4-hydroxyacetanilide or para-hydroxyacetanilide to an Industrial Chemist is an important end product as well as an important precursor used in the synthesis of some other Organic compounds. As an analgesic it has gained fame because it is readily available but then its adverse effect stands pronounced when it’s not taken in its rightful dosage or when it is taken in addition to some other food or drug. This article talks about the historical changes this important compound has undergone till date, its preparation by the chemist, some reactions it undergoes in the presence of some other precursors, its Dozage, Its adverse effect as well as its usage. This is a very helpful drug which becomes a poison in the presence of other drugs such as warfarin and care should be taken when handling this drug.
Abstract: N-acylated aromatic amines (those having an acyl group, RCO- substituted on nitrogen) are important in over-the-counter headache remedies. Over-the-counter drugs are those you may buy without a prescription. Paracetamol is virtually the sole survivor of the so-called “aniline derivatives” or “aniline analgesics” which are; acetanilide, phenacetin a...
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