In attempt to improve the biological activity of the well-known drug hydroxychloroquine (HQC), eight derivatives (HQ1-4Py – HQ8-4Py) based on the core of HQC were design and their electronic properties including frontier molecular orbitals, total energy and structural parameters were estimated at semi-empirical PM3 levels. Pharmacological parameters such as physicochemical, pharmacokinetics, drug-likeness and medicinal chemistry friendliness have been evaluated to estimate the drugs similarity. Introducing these moieties affect both electronic and drug likeness properties, HQ5-Py shows promised properties such large Eg and good clogP, The obtained results show that the suggested derivates may represent a potential drug candidate for COVID-19.
Keywords: Molecular similarity, COVID-19, Hydroxychloroquine (HCQ).
Compounds with more than one bioactive motif become of great interest. In this regard, a new tridentate 1,2-unsymmetrical ligand consists of flexible and rigid bioactive arms spaced by benzene ring in an ortho position designed to form a bifunctional molecule. The 2-((3-(pyridin-2-yl)-1H-pyrazol-1-yl)methyl)benzonitrile (PPMB) synthesized under phase transfer reaction and characterized using 1H-NMR and mass spectroscopy and studied as potent kinase inhibitors. Theoretically, the molecule structure was investigated at the B3LYP/6-311++G(d,p) level of theory in the gas phase and revealed that all bond lengths and bond angles within the accepted limit. The frontier molecular orbitals (FMO) energies (HOMO and LUMO), energy gap, dipole moment, chemical softness and chemical hardness were calculated. Pharmacologically, the ligand activity was investigated in silico using SWISS ADME. Furthermore, the compound was docked into the transforming growth factor (TGF) beta type I receptor kinase active site to evaluate the ability of ligand as a kinase inhibitor.
Keywords: DFT, pyrazolyl-pyridine, physiochemical, properties molecular docking, bioactive molecules, unsymmetrical ligands
Background:
In this study, nine novel compounds, bearing N-[2-(4-substituted
piperazine-1-yl)acetyl]-N’-[bis-(4-fluorophenyl)methyl]piperazine structures were synthesized.
Methods:
Their cytotoxic properties were evaluated in vitro by NCI-60 Sulforhodamine B
(SRB) assay against human cancer cell lines: Huh7 (hepatocellular), MCF7 (breast) and HCT116
(colorectal).
Results and Conclusion:
According to the activity data, most of the compounds are more cytotoxic
than 5-fluorouracil against Huh7 and HCT116 cancer cell lines.
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