The molecular docking of 1,4-naphthoquinone derivatives as inhibitors of Polo-like kinase 1 using Molegro Virtual Docker.

Polo-like kinase 1 (Plk1) is over expressed in many types of human cancers, and has been implicated as an adverse prognostic marker for cancer patients. Plk1 is localized to its intracellular anchoring sites via its polo-box domain (PBD). The PBD of Plk1 has a crucial role in proper subcellular localization and mitotic functions of Plk1. Plk1 is the preferential target for inhibition of the mitotic processing therefore it can be chosen as drug target for the treatment of cancer. The aim of the study is to find plk1 inhibitor potential from naphthoquinone derivatives through binding free energy analysis into plk1 using molecular docking. We conducted docking simulation to naphthoquinone derivatives as ligands into plk1 as receptor. The 3D structure of plk1 was downloaded from PDB (Code ID:3THB). The structure of ligands and protein were prepared using ChemBioDrawUltra 12.0. Docking process, the interaction and binding of ligands – protein were done and visualized using software Molegro Virtual Docking.(MVD). The results showed no hydrogen bonding and electrostatic interaction between compound NO11(modified naphthoquinone) with Plk1, but this compound have more steric interaction with Phe 133, Asp 194, Glu 101, Lys 82, Cys 133 and Glu 140 of Plk1. Moldock scores of compound NO11, is -134.73 kcal/mol. It is predicted that compound NO11 has potency as lead compound to find a new anticancer candidates for possible therapeutic agents.

3-Dimensional QSAR and molecular docking studies of a series of indole analogues as inhibitors of human non-pancreatic secretory phospholipase A2.

Background: Design and development of new drugs is simplified and made more cost-effective because of the advances in the concepts of Quantitative Structure-Activity Relationship (QSAR) studies. A methodology of QSAR studies is one of the approaches to the rational drug design. Methods: 3-Dimensional QSAR studies were performed on a series of indole analogues as inhibitors of human non-pancreatic secretory phospholipaseA2 (PLA2) by using Scigress explorer software suite. Docking studies of these compounds were also performed to understand the interactions with amino acid residues of PLA2 protein. Results: The multiple linear regression analysis was used to correlate the physicochemical descriptors with the PLA2 inhibitory activity of 20 training set of compounds and the best QSAR model was developed. The best model was validated using leave-one-out method and found to be statistically significant, with coefficient of determination (r2) of 0.788. This model was further used to predict the PLA2 inhibitory activity of 12 test set of compounds. Docking analysis revealed that most of the compounds formed H-bond interactions with amino acid residues of PLA2 protein (PDB ID: 1DB4). Predicted pIC50 value of one of the test compounds was 7.454 and it showed H-bond interactions with Asp48, Cys44, His27, Gly29 and Gly31 residues. Conclusion: The present study shall help in rational drug design and synthesis of new selective PLA2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between PLA2 and the novel indole analogue compounds.

Docking studies of Physalis peruviana ethanol extract using molegro virtual docker on insulin tyrosine kinase receptor as antidiabetic agent.

Physalis peruviana Linn in Indonesia was better known as ciplukan, based on information from urban people in Indonesia is as antidiabetic. In the previeous studies, the levels of blood glucose in animals experimental of Physalis peruviana quantified with glucometer and compared with oral antidiabetic drugs gliclazide, showed that Gliclazide was decrease more levels of glucose significantly than ethanol extract of Physalis peruviana. We have done molecular docking using Molegro Virtual Docker (MVD) on ethanol extract of Physalis peruviana and gliclazide to compare between in silico and in vivo studies. Based on studies before the main content of the ethanol extract of Physalis peruviana were withanolide, 4-OH-withanolide, and perulactone. In this study the results showed that gliclazide had been better bond in insulin tyrosine kinase receptor than main content of Physalis peruviana which can be seen from Moldock score 105.217 and Rerank score -68,2931 means that the energy was lower and more stable binding. Moldock Score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -93.5472; 70.5843; 88.7881, respectively. Rerank score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -61.5149; -67.5345; -65.7979, respectively. The hydrogen bonds of withanolide, 4-OH-withanolide, perulactone and gliclazide with amino acid of insulin tyrosine kinase receptor were Phe 1186 and Thr 1186. Finally, in the 3D MVD visualization between main content of ethanol extract of Physalis peruviana and gliclazide can be concluded that interaction of gliclazide was more harmonious than main content of ethanol extract Physalis peruviana.

3-Dimensional quantitative structure-activity relationship and molecular docking studies of tetrasubstituted pyrazole derivatives as inhibitors of cyclooxygenase-2.

Background: Design and development of new drugs is simplified and made more cost-effective because of the advances in the concepts of Quantitative Structure-Activity Relationship (QSAR) studies. A methodology of QSAR studies is one of the approaches to the rational drug design. Methods: 3-Dimensional QSAR studies were performed on a series of tetrasubstituted pyrazole derivatives by using Scigress Explorer software suite. Docking studies of these compounds were also performed to understand the interactions with amino acid residues of COX-2 protein. Results: The multiple linear regression analysis was used to correlate the physicochemical descriptors with the COX-2 inhibitory activity of 24 training set of compounds and the best QSAR model was developed. The best model was validated using leave-one-out method and found to be statistically significant, with coefficient of determination (r2) of 0.835. This model was further used to predict the COX-2 inhibitory activity of 10 test set of compounds. Docking analysis revealed that most of the compounds formed H-bond interactions with amino acid residues of COX-2 protein (PDB ID: 1CX2). Predicted pIC50 value of one of the test compounds was 7.048 and it showed H-bond interactions with His90 & Tyr355 residues. Conclusion: The present study shall help in rational drug design and synthesis of new selective COX-2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between COX-2 and the novel tetrasubstituted pyrazole derivative compounds.

Docking studies of Physalis peruviana ethanol extract using molegro virtual docker on insulin tyrosine kinase receptor as antidiabetic agent.

Physalis peruviana Linn in Indonesia was better known as ciplukan, based on information from urban people in Indonesia is as antidiabetic. In the previeous studies, the levels of blood glucose in animals experimental of Physalis peruviana quantified with glucometer and compared with oral antidiabetic drugs gliclazide, showed that Gliclazide was decrease more levels of glucose significantly than ethanol extract of Physalis peruviana. We have done molecular docking using Molegro Virtual Docker (MVD) on ethanol extract of Physalis peruviana and gliclazide to compare between in silico and in vivo studies. Based on studies before the main content of the ethanol extract of Physalis peruviana were withanolide, 4-OH-withanolide, and perulactone. In this study the results showed that gliclazide had been better bond in insulin tyrosine kinase receptor than main content of Physalis peruviana which can be seen from Moldock score 105.217 and Rerank score -68,2931 means that the energy was lower and more stable binding. Moldock Score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -93.5472; 70.5843; 88.7881, respectively. Rerank score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -61.5149; -67.5345; -65.7979, respectively. The hydrogen bonds of withanolide, 4-OH-withanolide, perulactone and gliclazide with amino acid of insulin tyrosine kinase receptor were Phe 1186 and Thr 1186. Finally, in the 3D MVD visualization between main content of ethanol extract of Physalis peruviana and gliclazide can be concluded that interaction of gliclazide was more harmonious than main content of ethanol extract Physalis peruviana.