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Quarterly published in print and online "Inventi Impact: Molecular Modeling" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals.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\ninfection. Plasmodium falciparum is the most common parasite affecting people and lead to the death of million people annually.\nQuinoline is the common scaffold used for the treatment of malaria. In this study QSAR analysis of various quinoline analogues\nwas performed to know the remarkable impact of different physicochemical properties on bioactivity. The model was generated\nusing buildQSAR and the required equation was also obtained with good correlation coefficient between calculated and\nobserved values of activity....
Topoisomerase is a critical enzyme, vital for DNA replication and consequently playing a pivotal role in oncology.\nBeing a validated target in anticancer drug discovery and having a well-established link between the higher enzyme activity and\nmalignancy, topoisomerase has become an excellent target to inhibit. In this study, a series of 21 topoisomerase I inhibitors,\nhaving indenoisoquinoline ring system as the parent scaffold, was taken for molecular modeling. Molecular characteristics such\nas steric, electrostatic and hydrogen bonding and their influence on afforded biological activity were established using 3D QSAR\ntechniques; comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA).\nTop1 inhibition and indenoisoquinoline ring may make these molecules potential molecules in oncology. A statistically\ncomprehensive and robust model was developed having significant r2and r2pred values giving better insights of spatially focal\nregions around the scaffold which directly have an effect on the degree of biological activity. Segregating the series into test and\ntraining sets allowed calculations authenticating the predictive ability of the developed model. Coloured contour maps and\nstatistical 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\nHDLs to proatherogenic apolipoprotein B. A deficiency of CETP is associated with increased HDL levels and decreased LDL\nlevels, a profile that is typically antiatherogenic. Inhibition of CETP may act as potential target for antihyperlipidemic drug\ndesign. 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....
Background. The development of new therapeutic strategies to treat patients for leishmaniasis has become a priority. The\nantileishmanial activity of the strychnobiflavone flavonoid was recently demonstrated against Leishmania amazonensis and\nLeishmania infantum amastigotes and promastigotes. The biological effect of this molecule was identified due to its capacity\nto interfere in the parasite mitochondrial membrane; however, the underlying molecular mechanism remains unclear. Methods\nand Results. In this study, a computational approach using bioinformatics was performed to screen biological targets of\nstrychnobiflavone in L. infantum. Computational programs, such as the target fishing approach and molecular docking assays,\nwere used. Results showed that the putative pathway targeted by strychnobiflavone in L. infantum is themethylglyoxal degradation\nsuperpathway, and one hydrolase-like protein was predicted to be the molecular target of this flavonoid in the parasites. Conclusion.\nIn this context, this study provides the basis for understanding the mechanism of action of strychnobiflavone in L. infantum and\npresents a strategy based on bioinformatics programs to screen targets of other molecules with biological action against distinct\npathogens....
Metalloprotease enzyme play an important role in tissue remolding associated with various process such as morphogenesis, angiogenesis, tissue repair, arthritis and metastasis. In cancer elaboration of metalloprotease takes place . In present study the docking study was performed on 14 Schiff bases of dapsone and their substituted 2-azetidinone with metalloprotease enzyme. The binding conformation of Schiff bases of dapsone and their substituted 2-azetidinone for the inhibition of metalloprotease enzyme for predicting the role of dapsone and their derivative as new potential inhibitors useful as anticancer agent was performed by using Molegro Virtual Docker MVD (Molegro Aps). The binding was determined and predicted by molecular docking. Best docking scores were shown by molecule 1a and 2c....
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