Frequency: Quarterly E- ISSN: 2250-0308 P- ISSN: 2249-359X IBI Factor: 4.2 Abstracted/ Indexed in: Ulrich's International Periodical Directory, Google Scholar, SCIRUS, Genamics Journal Seek, PSOAR, getCITED, InfoBase Index
Quarterly published in print and online "Inventi Impact: Molecular Modeling" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals. The journal includes all aspects of molecular modeling and computational chemistry, including study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, QSAR, structure-activity and structure-property relationships, database mining, and compound library design.
Background: An increased incidence of fungal infections, both invasive and superficial, has been witnessed over\r\nthe last two decades. Candida species seem to be the main etiology of nosocomial fungal infections worldwide\r\nwith Candida albicans, which is commensal in healthy individuals, accounting for the majority of invasive Candida\r\ninfections with about 30-40% of mortality.\r\nResults: New aromatic and heterocyclic esters 5a-k of 1-aryl-3-(1H-imidazol-1-yl)propan-1-ols 4a-d were successfully\r\nsynthesized and evaluated for their anti-Candida potential. Compound 5a emerged as the most active congener\r\namong the newly synthesized compounds 5a-k with MIC value of 0.0833 �µmol/mL as compared with fluconazole\r\n(MIC value >1.6325 �µmol/mL). Additionally, molecular modeling studies were conducted on a set of anti-Candida\r\nalbicans compounds.\r\nConclusion: The newly synthesized esters 5a-k showed more potent anti-Candida activities than fluconazole.\r\nCompounds 7 and 8 revealed significant anti-Candida albicans activity and were able to effectively satisfy the\r\nproposed pharmacophore geometry, using the energy accessible conformers (Econf < 20 kcal/mol)....
HIV-1 (human immunodeficiency virus type-1) is the pathogenic retrovirus and causative agent of AIDS. The integrase enzyme offers an attractive target for anti-AIDS drug design because of its necessary for viral life cycle and lack of IN homologous enzymes in the human host. Structural features of L-chicoric acid are important for potency against HIV-1 integrase. So, in the present study, 2-D QSAR and interaction studies of some chicoric acid analogs was carried out by VLife MDS & Schrodinger molecular modeling interface. The developed QSAR models showed r2= 0.8503, pred_r2 = 0.8201 with MLR analysis. Docking study also revealed important interactions of these ligands with the active binding site of integrase enzyme. These studies are more significant guide to trace the features that really matter especially with respect to the design of novel compounds....
The �²3 adrenergic receptor is raising as an important drug target for the treatment of\npathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several\nattempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron\nis the only available drug on the market that targets this receptor approved for the treatment of\noveractive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA\n(Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially\nlife-threatening side effects associated with the administration of Mirabegron, casting doubts on the\ncontinuity of this compound. Therefore, it is of utmost importance to gather information for the\nrational design and synthesis of new �²3 adrenergic ligands. Herein, we present the first combined\n2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA\n(three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity\nIndex Analysis) study on a series of potent �²3 adrenergic agonists of indole-alkylamine structure.\nWe found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor,\nlipophilicity and molar refractivity properties of the compounds to generate new promising molecules.\nFinally, based on our analysis, a summary and a regiospecific description of the requirements for\nimproving �²3 adrenergic activity is given....
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....
In the search for fused heterocycle molecules with potential biological activities, the new title compound was produced in racemic form via a four step-synthetic sequence with an overall yield of 60%. It was structurally characterised via 1H-, 13C-NMR and IR analyses, and the molecular composition was confirmed through a high-resolution MS experiment. After predicting its analgesic activity using PASS online software, wherein a good overlap between its enantiomers and the structure of the natural opioid morphine was observed, the compound was evaluated through docking calculations as a ligand of the μ-opioid receptor. The resulting energy values and interactions were comparable to the data obtained for morphine and its synthetic derivative fentanyl, which is used in the therapeutic treatment of severe forms of pain. Moreover, the title compound displayed favourable predicted blood–brain barrier permeation and drug-likeness....
Topoisomerase is a critical enzyme vital for DNA replication and consequently playing a pivotal role in oncology. Being a validated target in anticancer drug discovery and having a well-established link between the higher enzyme activity and malignancy, topoisomerase has become an excellent target to inhibit. In this study, a series of 21 topoisomerase I inhibitors, having Indenoisoquinoline ring system as the parent scaffold, was taken for molecular modeling. Molecular characteristics such as steric, electrostatic and hydrogen bonding and their influence on afforded biological activity were established using 3D QSAR techniques; comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Top1 inhibition and indenoisoquinoline ring may make these molecules potential molecules in oncology. A statistically comprehensive and robust model was developed having significant r2 and r2pred values giving better insights of spatially focal regions around the scaffold which directly have an effect on the degree of biological activity. Segregating the series into test and training sets allowed calculations authenticating the predictive ability of the developed model. Coloured contour maps and statistical analyses might provide substantial assistance in developing better molecules with similar structures in future....
Cholesteryl ester transfer protein (CETP) is responsible for the transfer of cholesteryl esters from antiatherogenic HDLs to proatherogenic apolipoprotein B. A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. Inhibition of CETP may act as potential target for antihyperlipidemic drug design. The current manuscript deals with the 3D QSAR, pharmacophore identification of some reported CETP inhibitors....
As part of our research for new leads against human African trypanosomiasis (HAT),\nwe report on a 3D-QSAR study for antitrypanosomal activity and cytotoxicity of aminosteroid-type\nalkaloids recently isolated from the African medicinal plant Holarrhena africana A. DC. (Apocynaceae),\nsome of which are strong trypanocides against Trypanosoma brucei rhodesiense (Tbr), with low toxicity\nagainst mammalian cells. Fully optimized 3D molecular models of seventeen congeneric Holarrhena\nalkaloids were subjected to a comparative molecular field analysis (CoMFA). CoMFA models were\nobtained for both, the anti-Tbr and cytotoxic activity data. Model performance was assessed in\nterms of statistical characteristics (R2, Q2, and P2 for partial least squares (PLS) regression, internal\ncross-validation (leave-one-out), and external predictions (test set), respectively, as well as the\ncorresponding standard deviation error in prediction (SDEP) and F-values). With R2 = 0.99, Q2 = 0.83\nand P2 = 0.79 for anti-Tbr activity and R2 = 0.94, Q2 = 0.64, P2 = 0.59 for cytotoxicity against L6 rat\nskeletal myoblasts, both models were of good internal and external predictive power. The regression\ncoefficients of the models representing the most prominent steric and electrostatic effects on anti-Tbr\nand for L6 cytotoxic activity were translated into contour maps and analyzed visually, allowing\nsuggestions for possible modification of the aminosteroids to further increase the antitrypanosomal\npotency and selectivity. Very interestingly, the 3D-QSAR model established with the Holarrhena\nalkaloids also applied to the antitrypanosomal activity of two aminocycloartane-type compounds\nrecently isolated by our group from Buxus sempervirens L. (Buxaceae), which indicates that these\nstructurally similar natural products share a common structureââ?¬â??activity relationship (SAR) and,\npossibly, mechanism of action with the Holarrhena steroids. This 3D-QSAR study has thus resulted in\nplausible structural explanations of the antitrypanosomal activity and selectivity of aminosteroidand\naminocycloartane-type alkaloids as an interesting new class of trypanocides and may represent\na starting point for lead optimization....
Background: Tremendous research from last twenty years has been pursued to cure human life against HIV virus. A\r\nlarge number of HIV protease inhibitors are in clinical trials but still it is an interesting target for researchers due to\r\nthe viral ability to get mutated. Mutated viral strains led the drug ineffective but still used to increase the life span\r\nof HIV patients.\r\nResults: In the present work, 3D-QSAR and docking studies were performed on a series of Danuravir derivatives,\r\nthe most potent HIV- protease inhibitor known so far. Combined study of 3D-QSAR was applied for Danuravir\r\nderivatives using ligand-based and receptor-based protocols and generated models were compared. The results\r\nwere in good agreement with the experimental results. Additionally, docking analysis of most active 32 and least\r\nactive 46 compounds into wild type and mutated protein structures further verified our results. The 3D-QSAR and\r\ndocking results revealed that compound 32 bind efficiently to the wild and mutated protein whereas, sufficient\r\ninteractions were lost in compound 46.\r\nConclusion: The combination of two computational techniques would helped to make a clear decision that\r\ncompound 32 with well inhibitory activity bind more efficiently within the binding pocket even in case of mutant\r\nvirus whereas compound 46 lost its interactions on mutation and marked as least active compound of the series.\r\nThis is all due to the presence or absence of substituents on core structure, evaluated by 3D-QSAR studies. This set\r\nof information could be used to design highly potent drug candidates for both wild and mutated form of viruses....
Asthma is a chronic inflammatory illness characterised by airway constriction and alterations in immune cells, including eosinophil, neutrophils, macrophages, lymphocytes and cytokines. Globally, asthma prevalence is increasing, with industrialised countries having the highest frequency. Therefore, it was crucial to find a unique medication made from plants that had the fewest negative effects. With the help of computational methods, we attempted to create therapeutic molecules for asthma from plant chemicals in this effort. First, 80 phytoconstituents from various medicinal plants were discovered; these compounds were then further examined for the Lipinski rule of 5 (Rule for oral drug molecules). According to the Lipinski rule's results, only 34 out of the 80 compounds satisfy the conditions of an oral drug. Additional build QSAR tests were conducted for 34 compounds from medicinal plants and the results showed that only 4 of the compounds lie on the regression line in the graph, which was predicted to forecast the 4 best bindings to the targets. Then the finding of QSAR analysis was docked with Interleukin-13 protein using Argus lab Software. The most favourable docked confirmation was selected and further conformation were analysed for its binding interactions between ligands and targets using PyMol. Finally, the results of QSAR and Docking were assessed and the best compounds were observed to possess anti-asthmatic efficacy....
Loading....