ABSTRACT:The structure and chemical reactivity of some selected cis-platinum (II) complexes, including clinically used drug molecules, cisplatin, carboplatin, and oxaliplatin are investigated using density functional theory (DFT) calculations. Calculated geometries of the complexes are in agreement with their available X-ray data. The global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity are calculated to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the complexes. Inclusion of solvent effect shows that both global and local descriptors change the trend of reactivity with respect to their trend in the gas phase. The stability of the complexes increases with the inclusion of water molecules. Simple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on DFT derived electrophilicity index for the Pt(II) complexes against A2780 human ovarian adenocarcinoma cell line to establish the importance of the descriptor in predicting cytotoxicity.
Cytotoxic activities of cis-platinum complexes against parental and resistant ovarian cancer cell lines were investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) based descriptors. The calculated parameters were found to increase the predictability of each QSAR model with incorporation of solvent effects indicating its importance in studying biological activity. Given the importance of logarithmic n-octanol/water partition coefficient (log P(o/w)) in drug metabolism and cellular uptake, we modeled the log P(o/w) of 24 platinum complexes with different leaving and carrier ligands by the quantitative structure-property relationship (QSPR) analysis against five different concentrations of MeOH using DFT and molecular mechanics derived descriptors. The log P(o/w) values of an additional set of 20 platinum complexes were also modeled with the same descriptors. We investigated the predictability of the model by calculating log P(o/w) of four compounds in the test set and found their predicted values to be in good agreement with the experimental values. The QSPR analyses performed on 24 complexes, combining the training and test sets, also provided significant values for the statistical parameters. The solvent medium played an important role in QSPR analysis by increasing the internal predictive ability of the models.
In this study, antimycobacterial activity of a set of synthesized chalcone derivatives against Mycobacterium tuberculosis H37Rv was investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) and molecular mechanics (MM+)-based descriptors in both gas and solvent phases. The best molecular descriptors identified were hardness, E HOMO , MR A-4 and MR B-4¢ that contributed to the antimycobacterial activity of the chalcones as independent factors. The correlation of these four descriptors with their antimycobacterial activity increases with the inclusion of solvent medium, indicating their importance in studying biological activity. QSAR models revealed that in gas phase, lower values of E HOMO , MR A-4 and MR B-4¢ increase the antimycobacterial activity of the chalcone molecules. However, in solvent phase, lower values of E HOMO and MR B-4¢ and higher values of MR A-4 increase their activity.
In the present work multiple linear regression analyses were performed to build QSAR models for nucleoside analogous using density functional theory (DFT) and molecular mechanics (MM+) based descriptors in both gas and solvent phases. The QSAR models for 14 carbocyclic analogues of nucleosides against murine leukemia cell line (L1210/0) and human T-lymphocyte cell lines (Molt4/C8 and CEM/0) explain more than 90% of the variances in the activity data along with higher values of [Formula: see text]. The energy of the next lowest unoccupied molecular orbital (E(NL)), electrophilicity (omega) and van der Waals surface area (SA) are the main independent factors contributing to the anticancer activity of nucleoside analogues. Inclusion of solvent medium increases the correlation of each descriptor with activity. Based on the key features responsible for anticancer activity, 10 new compounds with rather high anticancer activity have been theoretically designed. Cytotoxic activities of an additional set of 20 nucleoside analogues were also modeled by the same descriptors and found their predicted values to be in good agreement with the experimental values.
Artemisinin form the most important class of antimalarial agents currently available, and is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many derivatives of artemisinin were prepared. A comparative study on the chemical reactivity of artemisinin and some of its derivatives is performed using density functional theory (DFT) calculations. DFT based global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries are used to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the molecules. Multiple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on the DFT based descriptors against the chloroquine-resistant, mefloquine-sensitive Plasmodium falciparum W-2 clone.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.