Various invitro and computational methods were implemented to evaluate the anticancer potential of anthocyanidins, namely cyanidin, malvidin, delphinidin, peonidin, pelargonidin, and petunidin. These anthocyanidins were docked with CDK-2, CDK-6 and IGF-1R kinase proteins. Additionally, known inhibitors (KIs) such as SU9516, Palbociclib, OSI-906 are compared with their respective macromolecules, including, CDK-2, CDK-6 and IGF-1R kinase, in to compare results of the study based on Lipinski rule of 5. The Auto Dock Tool (Autodock 4) was used for molecular docking, and the docked complex compounds were visualised and interpreted using the Bio via Discovery Studio 2020 client. The Docking results obtained showed a very good inhibitory binding to almost all the selected cancer proteins, and these compounds might be a potential drug molecule.
Alzheimer's disease is characterized by loss of neurons and synapses in the cerebral cortex and certain sub cortical regions. The earliest observable symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress. As the disease advances, symptoms include confusion, irritability and aggression, long-term memory loss. Two drugs specifically approved for treating Alzheimer's disease were Tacrine and Donezepil. Tacrine mainly inhibit the histamine-N-methyltransferase protein which block the histamine transmission. Donepezil inhibit the acetyl cholinesterase which degrades the acetylcholine transmitter. In this study, computational methods are used to design novel tacrine and donepezil derivatives and evaluated them for interaction with the Histamine-N-methyltransferase protein and acetyl cholinesterase protein respectively through insilico analysis by using Hyperchem 8.0, Gold 3.01 docking software. The result of the docking studies shows that ligands of T3 and D3 with R -CH2CH3 are having highest binding affinity.
The Bcr-Abloncoprotein with constitutive tyrosine kinase activity plays a pivotal role in the pathogenesis of chronic myeloid leukemia (CML), therefore being an ideal target for the drug development. Imatinibmesylate, a selective tyrosine kinases inhibitor (TKI), has excellent efficacy in the treatment of chronic myeloid leukemia. It has opened the way to the development of additional TKIs against chronic myeloid leukemia, including nilotinib and dasatinib. In this study, computational methods are used to design novel imatinib derivatives and evaluated them for interaction with the Bcr-Abloncoprotein through insilico analysis by using Hyperchem 8.0, Gold 3.01 docking software. Here, from the results, it is reported that 1, 14, 26, ligands are having dock score near to imatinib and modifications to these ligands may result in better ligands than imatinib. The results of Toxicity studies also supported 1, 14, 26, better drug-likeness properties. Ligand 4 has shown higher affinity and better interaction with Bcr-Abloncoprotein than imatinib and any other newly designed molecules, but it had shown mutagenicity and irritancy.
Epidermal Growth Factor Receptor (EGFR) is a member of the EGFR/HER family of receptor tyrosine kinases (RTKs) plays an important role in normal organogenesis and in neoplastic processes of cell proliferation, inhibition of apoptosis, angiogenesis, and metastatic spread. EGFR expression is frequent in Non-Small Cell Lung Cancers (NSCLC) and over expression is observed in 32-79% of NSCLC patients. In the present study, attempts are made to identify ligands with Phenylquinazoline moiety having better inhibition of EGFR using computational methods. A set of 27 molecules are designed and docked with the EGFR protein. ADME and Toxicity studies are performed by using Discovery Studio 2.5. 11 ligands like 1, 2, 3, 6, 7, 9, 13, 17, 19, 24 and 25 have shown better Dock score when compared to gefitinib, a marketed potent EGFR inhibitor, in which Ligand-1, N-(4-bromo-2- fluorophenyl)-6-methoxy-7-((1-methyl-1,2- dihydropyridin-4-yl)methoxy)quinazolin-4-amine is having highest Dock score of 62.131. Ligands like 1, 2 and 24 is having better docking scores and the results of Toxicity studies also supported this ligands having better drug-likeness properties, modifications to these ligands may result in better ligands than gefitinib.
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