Exploring structural requirements of aurone derivatives as antimalarials by validated DFT-based QSAR, HQSAR, and COMFA–COMSIA approach

Adhikari, Nilanjan; Halder, Amit Kumar; Mondal, Chanchal; Jha, Tarun

doi:10.1007/s00044-013-0590-8

Cited by 26 publications

(18 citation statements)

References 43 publications

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“…Aurones, 2‐benzylidenebenzofuran‐3(2 H )‐ones, as structural isomers of flavones are distributed in plants and contribute to yellow coloration of flowers and fruits . They possess diverse biological activities, including antioxidant, anticancer, and antimalarial properties . They are also described as phytoalexins against infections of plants and used for the treatment of Alzheimer's disease and as inhibitors of hepatitis C virus…”

Section: Methodsmentioning

confidence: 99%

Novel Synthesis of Aurones by 2‐PyONa‐catalyzed Regioselective Cyclization of o‐(Alkynon‐1‐yl)phenols

Lee

2018

Bulletin Korean Chem Soc

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Section: Methodsmentioning

confidence: 99%

Novel Synthesis of Aurones by 2‐PyONa‐catalyzed Regioselective Cyclization of o‐(Alkynon‐1‐yl)phenols

Lee

2018

Bulletin Korean Chem Soc

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“…It correlates structural and physicochemical properties with experimental activities. It is extensively used to develop predictive models for chemical compounds with experimental biological activities (Adhikari, Halder, Mondal, & Jha, 2013;Halder, Adhikari, & Jha, 2010;Halder, Saha, & Jha, 2013a, 2013bJana et al, 2011;Lewis & Wood, in press). …”

Section: D-qsar Studymentioning

confidence: 99%

Stepwise development of structure–activity relationship of diverse PARP-1 inhibitors through comparative and validatedin silico modeling techniques and molecular dynamics simulation

Halder

Saha

et al. 2014

Journal of Biomolecular Structure and Dynamics

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Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) enzyme are useful for the treatment of various diseases including cancer. Comparative in silico studies were performed on different ligand-based (2D-QSAR, Kernel-based partial least square (KPLS) analysis, Pharmacophore Search Engine (PHASE) pharmacophore mapping), and structure-based (molecular docking, MM-GBSA analyses, Gaussian-based 3D-QSAR analyses on docked poses) modeling techniques to explore the structure-activity relationship of a diverse set of PARP-1 inhibitors. Two-dimensional (2D)-QSAR highlighted the importance of charge topological index (JGI7), fractional polar surface area (JursFPSA3), and connectivity index (CIC2) along with different molecular fragments. Favorable and unfavorable fingerprints were demonstrated in KPLS analysis, whereas important pharmacophore features (one acceptor, one donor, and two ring aromatic) along with favorable and unfavorable field effects were demonstrated in PHASE-based pharmacophore model. MM-GBSA analyses revealed significance of different polar, non-polar, and solvation energies. Docking-based alignment of ligands was used to perform Gaussian-based 3D-QSAR study that further demonstrated importance of different field effects. Overall, it was found that polar interactions (hydrogen bonding, bridged hydrogen bonding, and pi-cation) play major roles for higher activity. Steric groups increase the total contact surface area but it should have higher fractional polar surface area to adjust solvation energy. Structure-based pharmacophore mapping spotted the positive ionizable feature of ligands as the most important feature for discriminating highly active compounds from inactives. Molecular dynamics simulation, conducted on highly active ligands, described the dynamic behaviors of the protein complexes and supported the interpretations obtained from other modeling analyses. The current study may be useful for designing PARP-1 inhibitors.

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“…Other considered targets include agonists/antagonists of various GPCRs (85), nuclear hormone receptors (93), Ion channel inhibitors (105), and some other less prominent enzymes for which the annotations are kept as in the original paper. Also, annotations for aspartic protease (41), cysteine protease (50), dihydroorotate dehydrogenase (20), dihydrofolate reductase (8), DNA gyrase (15) and tRNA synthetases (13) are considered.…”

Section: Mode Of Action Annotationsmentioning

confidence: 99%

“…Currently, most studies available in the literature report QSARs for antimalarial compounds of one family at a time in a consistent biological experiment: substituted 4‐aminoquinolines, naphthoquinone derivatives, endochins, sulfonamides, urea derivatives, analogues of other used drugs . Different methods and molecular descriptors may be used: quantum chemistry level QSAR is applied quite extensively, from DFT to lightweight CODESSA quantum descriptors . 3D QSAR is a popular approach for this difficult medicinal chemistry problem .…”

Section: Introductionmentioning

confidence: 99%

AntiMalarial Mode of Action (AMMA) Database: Data Selection, Verification and Chemical Space Analysis

Sidorov

Davioud‐Charvet²,

Marcou

et al. 2018

Molecular Informatics

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This paper presents the effort of collecting and curating a data set of 15461 molecules tested against the malaria parasite, with robust activity and mode of action annotations. The set is compiled from in-house experimental data and the public ChEMBL database subsets. We illustrate the usefulness of the dataset by building QSAR models for antimalarial activity and QSPR models for modes of actions, as well as by the analysis of the chemical space with the Generative Topographic Mapping method. The GTM models perform well in prediction of both activity and mode of actions, on par with the classical SVM methods. The visualization of obtained maps helps to understand the distribution of molecules corresponding to different modes of action: molecules with similar targets are located close to each other on the map. Therefore, this analysis may suggest new modes of action for non-annotated or even annotated compounds. In perspective, this can be used as a tool for prediction of both antimalarial activity and target for novel, untested compounds.

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Exploring structural requirements of aurone derivatives as antimalarials by validated DFT-based QSAR, HQSAR, and COMFA–COMSIA approach

Cited by 26 publications

References 43 publications

Novel Synthesis of Aurones by 2‐PyONa‐catalyzed Regioselective Cyclization of o‐(Alkynon‐1‐yl)phenols

Novel Synthesis of Aurones by 2‐PyONa‐catalyzed Regioselective Cyclization of o‐(Alkynon‐1‐yl)phenols

Stepwise development of structure–activity relationship of diverse PARP-1 inhibitors through comparative and validatedin silico modeling techniques and molecular dynamics simulation

AntiMalarial Mode of Action (AMMA) Database: Data Selection, Verification and Chemical Space Analysis

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