Current Issue : October - December Volume : 2016 Issue Number : 4 Articles : 7 Articles
Malaria is the most fatal disease; in 2012 it was transmitted to 103 countries, with 3.4 billion people at risk of infection. Plasmodium falciparum is the most common parasite affecting people and lead to the death of million people annually. Quinoline is the common scaffold used for the treatment of malaria. In this study QSAR analysis of various quinoline analogues was performed to know the remarkable impact of different physicochemical properties on bioactivity. The model was generated using buildQSAR and the required equation was also obtained with good correlation coefficient between calculated and observed values of activity....
Novel PPAR-γ agonists have been designed and docking studies of the compounds have been performed. The pharmacophore having phenoxy linker and TZD ring has been retained and the lipophilic tail has been modified by various fatty acids. The designed ligands show mainly vander wall’s interactions and hydrogen bonding. All the designed compounds show good binding with the receptor. The designed ligands promise to be potent ligands for antihyperglycemic evaluation....
A series of halogen-directed donepezil drugs has been designed to inhibit acetyl\ncholinesterase (AChE). Density Functional theory (DFT) has been employed to optimize\nthe chair as well as boat conformers of the parent drug and modified ligands at B3LYP/\nMidiX and B3LYP/6-311G + (d,p) level of theories. Charge distribution, dipole moment,\nenthalpy, free energy and molecular orbitals of these ligands are also investigated to\nunderstand how the halogen-directed modifications impact the ligand structure and\ngovern the non-bonding interactions with the receptors. Molecular docking calculation\nhas been performed to understand the similarities and differences between\nthe binding modes of unmodified and halogenated chair-formed ligands. Molecular\ndocking indicated donepezil and modified ligands had non-covalent interactions with\nhydrophobic gorges and anionic subsites of AChE. The ââ?¬â??CF3-directed ligand possessed\nthe most negative binding affinity. Non-covalent interactions within the ligandââ?¬â??receptor\nsystems were found to be mostly hydrophobic and Ãâ?¬- stacking type. F, Cl and ââ?¬â??CF3\ncontaining ligands emerge as effective and selective AChE inhibitors, which can\nstrongly interact with the two active sites of AChE. In addition, we have also investigated\nselected pharmacokinetic parameters of the parent and modified ligands....
Background: The persistent appearance of viral strains that causes a resistant viral infection has led to continuous trials\nfor the design and development of novel antiviral compounds. Benzoquinazoline compounds have been reported\nto exhibit an interesting antiviral activity. This work aims to study and evaluate the antiviral activity of a newly prepared\n2-thioxo-benzo[g]quinazolin-4(3H)-one series against herpes simplex (HSV-1 & 2) and coxsackievirus (CVB4).\nMethods: The antiviral activity was performed using the MTT assay, in which Vero cells (obtained from the American\nType Culture Collection, ATCC) were propagated in fresh Dulbeccoââ?¬â?¢s Modified Eagleââ?¬â?¢s Medium (DMEM) and challenged\nwith 104 doses of the virus. Thereafter, the cultures were treated simultaneously with two-fold serial dilutions of the\ntested compound and incubated at 37 Ã?°C for 48 h. Molecular docking studies were done on the CVB4 2A proteinase\nenzyme using Molegro Virtual Docker software.\nResults: The cytotoxicity (CC50), effective concentration (EC50) and the selectivity index (SI) values were determined.\nBased on their EC50 values, a number of the investigated compounds demonstrated weak to moderate activity relative\nto their parents. Accordingly, compounds 5ââ?¬â??9, 11, 15ââ?¬â??18, 21, 22, 24, 25, 27 and 28 were active against CVB4,\nand compounds 5 and 24 were active against HSV-1 and 2 in comparison to ribavirin and acyclovir, which were used\nas reference drugs.\nConclusion: The obtained results gave us some useful insights about the characteristic requirements for future trials\nto build up and design more active and selective antiviral 2-thioxo-benzo[g]quinazolin-4(3H)-one agents....
Molecular Modeling studies based on molecular mechanics and semi-empirical methods have been carried out for PGT and its metabolites in order to gain insight into excretion, reactivity and toxic effects of PGT. All metabolites are kinetically labile as indicated by LUMO-HOMO energy difference. The molecular modeling analysis shows that M2 metabolite is readily excreted in urine as its calculated solvation energy is highest. Further, it is found that M1 metabolite might be responsible for edema as it contains acidic group which can form salt bridge with Arg 120 of COX-1. All the metabolites are more reactive than PGT towards nucleophilic attack as indicated by lowest electron affinity of PGT. M3 has the highest HOMO (lowest ionization potential) energy so it will be most susceptible towards electrophilic attack....
Aim: QSAR techniques and docking increase the probability of success and reduce time and coast\nin drug discovery process. The study presents QSAR investigation on 20 pyrimidine derivatives for\nantitubercular activity against M. tuberculosis.\nMaterials and Methods: The relationship analysis between compounds and physicochemical\nproperties under study was done by two methods Multiple linear regression (MLR) and Step wise\nSelection of Terms (SW). The results show good models with six and five (SW) parameters linear\nequations. While the molecular docking simulation study of selected target Cytochrome P450\n14alpha-sterol demethylases (CYP51) of M. tuberculosis H37Rv(1E9X) and ligands (active\npyrimidine derivatives) as well as 4-Phenyl-1h-Imidazol for comparison was performed by using\nAutodock software.\nResults: The best model predicted in this study was the eq. 1 (MLR) with excellent statistical fit as\nSE = 9.06234 R-Sq = 94.9% R-Sq (adj) = 92.1% and F=34.107, while the best model by (SW)\nwas the eq. 2 with excellent statistical fit as SE= 8.89630 R-sq= 94.64% R-sq (adj)= 92.40% F=42.354. All the parameters showed insignificant role in the antitubercular activity. The molecular\ndocking of ligands 3a-j with the cytochrome P450 14alpha-sterol demethylases (CYP51) of\nM. tuberculosis H37Rv was examined and the best docked pose was shown to have one hydrogen\nbond with PRO386. While the compound 4-Phenyl-1h-Imidazolshowed lower scores of docker\nenergy.\nConclusion: Quantum chemical calculated parameters can be successfully used in the derived a\ndesigner QSAR. And the study indicated that predicted antitubercular activity values for pyrimidine\nderivative compounds can be modeled by two methods; stepwise (SW) and multiple linear\nregression (MLR), as well as the docking analysis showed that all compounds exhibited quite\nsimilar binding energy and compound 4 as best ligand which showed the highest binding energy\nand this agreement with experimental data. The most compounds understudy exhibit the best\nresults comparison with the ligand 4-Phenyl-1h-Imidazol.All the rustles could potentially offer a\nnew opportunity in the design of novel properties or extended to other compounds....
Malaria is considered as fatal disease, approximately 250 million clinical cases of malaria occur every year. The current trend suggests the use of herbal drugs for treatment of malaria; present study was aimed to screen the identified constituents for antimalarial activity using in-silico approach. Docking studies of the constituents were carried out using AutodockVina. Analysis of the results displayed that with the receptor, quinine was found to possess the least binding energy and hence the most potent antimalarial constituent among the series under study....
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