Sabarudin Ombe - Academia.edu (original) (raw)
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Papers by Sabarudin Ombe
Journal of Applied Pharmaceutical Science, 2019
Given the increasing role of P90 Ribosomal S6 Kinase 2 (RSK2) as an anticancer drug target, we pe... more Given the increasing role of P90 Ribosomal S6 Kinase 2 (RSK2) as an anticancer drug target, we performed 3D-Quantitative structure-activity relationship, including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) on difluorophenol pyridine derivatives as the inhibitor of RSK2. CoMFA model with q 2 of 0.597 and R 2 of 0.993, while CoMSIA model with q 2 of 0.563 and R 2 of 0.993, were obtained. The predictive ability of both models was assured using a test set compound with R 2 pred values of 0.996 each. Using the validated models, novel compound was proposed and its interaction with RSK2 was investigated employing molecular docking and molecular dynamics simulation of 50 ns. Furthermore, molecular-mechanics Poisson-Boltzmann surface area calculation was performed. The result showed that the newly designed compound has a comparable binding free energy with the known RSK2 inhibitor, indicating its potential as a new RSK2 inhibitor.
![Research paper thumbnail of Molecular modeling of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile as a dipeptidyl peptidase IV (DPP4) inhibitor](https://attachments.academia-assets.com/92788740/thumbnails/1.jpg)
](Journal of Applied Pharmaceutical Science, 2018
Research on the quantitative structure-activity relationship (QSAR) of the 4-fluoropyrrolidine-2-... more Research on the quantitative structure-activity relationship (QSAR) of the 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile as dipeptidyl peptidase IV (DPP4) inhibitor was performed. The molecular descriptors were calculated and the best QSAR model was developed, which satisfied statistical parameters such as correlation coefficient R = 0.912 and leave-one-out validation coefficients q 2 = 0.608. The predictive quality of the model was tested against test set compounds with R 2pred value of 0.7057. A novel compound (ND1) was designed and its predicted IC 50 was predicted, which was lower compared with that of the parent compound (S24). Molecular docking and molecular dynamics simulation of 40 ns showed the stability of binding orientation of ND1, the parent compound, and native ligand of DPP4. Prediction of affinity using molecular mechanics/Poisson-Boltzmann/surface area method revealed that the ND1 has a comparable affinity with the parent and natural ligands.
Journal of Applied Pharmaceutical Science, 2019
Given the increasing role of P90 Ribosomal S6 Kinase 2 (RSK2) as an anticancer drug target, we pe... more Given the increasing role of P90 Ribosomal S6 Kinase 2 (RSK2) as an anticancer drug target, we performed 3D-Quantitative structure-activity relationship, including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) on difluorophenol pyridine derivatives as the inhibitor of RSK2. CoMFA model with q 2 of 0.597 and R 2 of 0.993, while CoMSIA model with q 2 of 0.563 and R 2 of 0.993, were obtained. The predictive ability of both models was assured using a test set compound with R 2 pred values of 0.996 each. Using the validated models, novel compound was proposed and its interaction with RSK2 was investigated employing molecular docking and molecular dynamics simulation of 50 ns. Furthermore, molecular-mechanics Poisson-Boltzmann surface area calculation was performed. The result showed that the newly designed compound has a comparable binding free energy with the known RSK2 inhibitor, indicating its potential as a new RSK2 inhibitor.
Journal of Applied Pharmaceutical Science, 2018
Research on the quantitative structure-activity relationship (QSAR) of the 4-fluoropyrrolidine-2-... more Research on the quantitative structure-activity relationship (QSAR) of the 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile as dipeptidyl peptidase IV (DPP4) inhibitor was performed. The molecular descriptors were calculated and the best QSAR model was developed, which satisfied statistical parameters such as correlation coefficient R = 0.912 and leave-one-out validation coefficients q 2 = 0.608. The predictive quality of the model was tested against test set compounds with R 2pred value of 0.7057. A novel compound (ND1) was designed and its predicted IC 50 was predicted, which was lower compared with that of the parent compound (S24). Molecular docking and molecular dynamics simulation of 40 ns showed the stability of binding orientation of ND1, the parent compound, and native ligand of DPP4. Prediction of affinity using molecular mechanics/Poisson-Boltzmann/surface area method revealed that the ND1 has a comparable affinity with the parent and natural ligands.