scholarly journals In Silico Molecular Design, Synthesis, Characterization, and Rheology of Dendritically Branched Polymers: Closing the Design Loop

2012 ◽  
Vol 1 (3) ◽  
pp. 404-408 ◽  
Author(s):  
Lian R. Hutchings ◽  
Solomon M. Kimani ◽  
David M. Hoyle ◽  
Daniel J. Read ◽  
Chinmay Das ◽  
...  
Keyword(s):  
In Silico ◽  
Molecular Design ◽  
Branched Polymers ◽  
Design Synthesis

Correction to In Silico Molecular Design, Synthesis, Characterization, and Rheology of Dendritically Branched Polymers: Closing the Design Loop

2012 ◽  
Vol 1 (6) ◽  
pp. 742-742 ◽  
Author(s):  
Lian R. Hutchings ◽  
Solomon M. Kimani ◽  
David M. Hoyle ◽  
Daniel J. Read ◽  
Chinmay Das ◽  
...  
Keyword(s):  
In Silico ◽  
Molecular Design ◽  
Branched Polymers ◽  
Design Synthesis

scholarly journals Design, Synthesis, and In Silico Multitarget Pharmacological Simulations of Acid Bioisosteres with a Validated In Vivo Antihyperglycemic Effect

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 799
Author(s):  
Elix Alberto Domínguez-Mendoza ◽  
Yelzyn Galván-Ciprés ◽  
Josué Martínez-Miranda ◽  
Cristian Miranda-González ◽  
Blanca Colín-Lozano ◽  
...  
Keyword(s):  
In Silico ◽  
Molecular Design ◽  
Tyrosine Phosphatase ◽  
Binding Pocket ◽  
Binding Mode ◽  
Antidiabetic Activity ◽  
Design Synthesis ◽  
Consensus Analysis ◽  
Glucose Levels

Substituted phenylacetic (1–3), phenylpropanoic (4–6), and benzylidenethiazolidine-2,4-dione (7–9) derivatives were designed according to a multitarget unified pharmacophore pattern that has shown robust antidiabetic activity. This bioactivity is due to the simultaneous polypharmacological stimulation of receptors PPARα, PPARγ, and GPR40 and the enzyme inhibition of aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP-1B). The nine compounds share the same four pharmacophore elements: an acid moiety, an aromatic ring, a bulky hydrophobic group, and a flexible linker between the latter two elements. Addition and substitution reactions were performed to obtain molecules at moderated yields. In silico pharmacological consensus analysis (PHACA) was conducted to determine their possible modes of action, protein affinities, toxicological activities, and drug-like properties. The results were combined with in vivo assays to evaluate the ability of these compounds to decrease glucose levels in diabetic mice at a 100 mg/kg single dose. Compounds 6 (a phenylpropanoic acid derivative) and 9 (a benzylidenethiazolidine-2,4-dione derivative) ameliorated the hyperglycemic peak in a statically significant manner in a mouse model of type 2 diabetes. Finally, molecular dynamics simulations were executed on the top performing compounds to shed light on their mechanism of action. The simulations showed the flexible nature of the binding pocket of AR, and showed that both compounds remained bound during the simulation time, although not sharing the same binding mode. In conclusion, we designed nine acid bioisosteres with robust in vivo antihyperglycemic activity that were predicted to have favorable pharmacokinetic and toxicological profiles. Together, these findings provide evidence that supports the molecular design we employed, where the unified pharmacophores possess a strong antidiabetic action due to their multitarget activation.

Development of Novel Glitazones as Antidiabetic Agents: Molecular Design, Synthesis, Evaluation of Glucose Uptake Activity and SAR Studies

2020 ◽  
Vol 17 (7) ◽  
pp. 840-849
Author(s):  
Mahendra Gowdru Srinivas ◽  
Prabitha Prabhakaran ◽  
Subhankar Probhat Mandal ◽  
Yuvaraj Sivamani ◽  
Pranesh Guddur ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Molecular Design ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Ppar Γ ◽  
Sar Studies ◽  
Structure Activity ◽  
Uptake Activity

Background: Thiazolidinediones and its bioisostere, namely, rhodanines have become ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory were subjected to docking studies against PPAR-γ receptor for their selection. Methods and Results: As part of the synthesis of selected twelve glitazones, the core moiety, pyridine incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were prepared via Knovenageal condensation. In silico docking studies were performed against PPARγ protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1 cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window, glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic activity. Conclusion: Based on the glucose uptake results, structure activity relationships are drawn for the title compounds.

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Thiazole-Dihyrofuran Derivatives as Aromatase Inhibitors

2021 ◽  
pp. 105123
Author(s):  
Derya Osmaniye ◽  
Şennur Görgülü ◽  
Begum Nurpelin Saglik ◽  
Serkan Levent ◽  
Yusuf Ozkay ◽  
...  
Keyword(s):  
Aromatase Inhibitors ◽  
In Silico ◽  
Design Synthesis ◽  
In Silico Studies

scholarly journals Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators

2021 ◽  
Vol 36 (1) ◽  
pp. 1370-1377
Author(s):  
Daniel A. S. Kitagawa ◽  
Rafael B. Rodrigues ◽  
Thiago N. Silva ◽  
Wellington V. dos Santos ◽  
Vinicius C. V. da Rocha ◽  
...  
Keyword(s):  
In Silico ◽  
Design Synthesis ◽  
In Vitro Evaluation ◽  
In Silico Studies ◽  
Acetylcholinesterase Reactivators

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Triazoles as Anticancer Agents for Breast Cancer

2021 ◽  
pp. 131198
Author(s):  
Derya Osmaniye ◽  
Begum Nurpelin Saglik ◽  
Serkan Levent ◽  
Sinem Ilgın ◽  
Yusuf Ozkay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Agents ◽  
In Silico ◽  
Design Synthesis ◽  
In Silico Studies
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