3D QSAR and molecular docking studies of 4-alkoxy- and 4-acyloxy –phenyl ethylene thiosemicarbazone derivatives as tyrosinase inhibitors
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Three-dimensional quantitative structural–activity relationship studies were carried out to understand the factors affecting the activity of 4-alkoxy- and 4-acyloxy –phenyl ethylene thiosemicarbazone analogs. The quantitative structural activity relationship model has generated five points Pharmacophore features, having an excellent cross-validated correlation coefficient value (Q 2 = 0.8615), Pearson R (0.9577). This model also exhibited a high value of R 2 (0.9948), F-value (617.8), and lowest SD (0.089). The regression maps were developed on the basis of the best model and suggested aromatic electron withdrawing groups at the para position of phenyl ring which is crucial for Tyrosinase inhibitory activity. Toxicity and drug-likeness of these compounds were estimated by using OSIRIS molecular property explorer tool. The molecular modeling was performed by using Molegro Virtual Docker 2010.4.0. The binding pattern of the best active compound with Tyrosinase active site was analyzed and the residues HIS259, HIS85, His61, His263, VAL283, Glu322, Gly245, and Ala246 were found to have hydrophobic and hydrogen bond interactions.
Keywords3D-QSAR Pharmacophore hypotheses Molecular docking Drug-like properties Melanin Tyrosinase
One of the authors (MM) is thankful to University Grants Commission, New Delhi for financial support in the form of UGC-RGNF Junior Research Fellowship and the Head, Department of chemistry, University College of Science, Osmania University, for providing the laboratory facilities for carrying out research work.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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