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.

scholarly journals Novel glitazones as PPARγ agonists: molecular design, synthesis, glucose uptake activity and 3D QSAR studies

2018 ◽  
Vol 12 (1) ◽  
Author(s):  
Subhankar P. Mandal ◽  
Aakriti Garg ◽  
P. Prabitha ◽  
Ashish D. Wadhwani ◽  
Laxmi Adhikary ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Molecular Design ◽  
3D Qsar ◽  
Design Synthesis ◽  
Qsar Studies ◽  
Uptake Activity ◽  
Pparγ Agonists

Synthesis and antimicrobial activity of aryldiazenyl/arylhydrazono pyrazoles

2021 ◽  
Vol 45 (11-12) ◽  
pp. 1093-1099
Author(s):  
Abdulrhman Alsayari ◽  
Yahya I Asiri ◽  
Abdullatif Bin Muhsinah ◽  
Mohd. Zaheen Hassan
Keyword(s):  
Active Site ◽  
Phenyl Ring ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Docking Studies ◽  
Considerable Effect ◽  
Design Synthesis ◽  
Structure Activity ◽  
Antimicrobial Evaluation

We report the design, synthesis, and in vitro antimicrobial evaluation of functionalized pyrazoles containing a hydrazono/diazenyl moiety. Among these newly synthesized derivatives, 4-[2-(4-chlorophenyl)hydrazono]-5-methyl-2-[2-(naphthalen-2-yloxy)acetyl]-2,4-dihydro-3 H-pyrazol-3-one is a promising antimicrobial agent against Staphylococcus aureus (minimum inhibitory concentration 0.19 μg mL−1). Structure–activity relationship studies reveal that the electronic environment on the distal phenyl ring has a considerable effect on the antimicrobial potential of the hybrid analogues. Molecular docking studies into the active site of S. aureus dihydrofolate reductase also prove the usefulness of hybridizing a pyrazole moiety with azo and hydrazo groups in the design of new antimicrobial agents.

Molecular design, synthesis, and structure–Activity relationships leading to the potent and selective p56lck inhibitor BMS-243117

2003 ◽  
Vol 13 (13) ◽  
pp. 2145-2149 ◽  
Author(s):  
Jagabandhu Das ◽  
James Lin ◽  
Robert V. Moquin ◽  
Zhongqi Shen ◽  
Steven H. Spergel ◽  
...  
Keyword(s):  
Molecular Design ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Rational Design, Synthesis, Characterization and Evaluation of Iodinated 4,4′-Bipyridines as New Transthyretin Fibrillogenesis Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2213 ◽  
Author(s):  
Alessandro Dessì ◽  
Paola Peluso ◽  
Roberto Dallocchio ◽  
Robin Weiss ◽  
Giuseppina Andreotti ◽  
...  
Keyword(s):  
High Performance ◽  
Rational Design ◽  
Halogen Bond ◽  
Coupling Reaction ◽  
Docking Studies ◽  
Binding Modes ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Amyloid Fibril Formation ◽  
The Right

The 3,3′,5,5′-tetrachloro-2-iodo-4,4′-bipyridine structure is proposed as a novel chemical scaffold for the design of new transthyretin (TTR) fibrillogenesis inhibitors. In the frame of a proof-of-principle exploration, four chiral 3,3′,5,5′-tetrachloro-2-iodo-2′-substituted-4,4′- bipyridines were rationally designed and prepared from a simple trihalopyridine in three steps, including a Cu-catalysed Finkelstein reaction to introduce iodine atoms on the heteroaromatic scaffold, and a Pd-catalysed coupling reaction to install the 2′-substituent. The corresponding racemates, along with other five chiral 4,4′-bipyridines containing halogens as substituents, were enantioseparated by high-performance liquid chromatography in order to obtain pure enantiomer pairs. All stereoisomers were tested against the amyloid fibril formation (FF) of wild type (WT)-TTR and two mutant variants, V30M and Y78F, in acid mediated aggregation experiments. Among the 4,4′-bipyridine derivatives, interesting inhibition activity was obtained for both enantiomers of the 3,3′,5,5′-tetrachloro-2′-(4-hydroxyphenyl)-2-iodo-4,4′-bipyridine. In silico docking studies were carried out in order to explore possible binding modes of the 4,4′-bipyridine derivatives into the TTR. The gained results point out the importance of the right combination of H-bond sites and the presence of iodine as halogen-bond donor. Both experimental and theoretical evidences pave the way for the utilization of the iodinated 4,4′-bipyridine core as template to design new promising inhibitors of TTR amyloidogenesis.

Design, synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

2019 ◽  
Vol 49 (17) ◽  
pp. 2219-2234
Author(s):  
Srinu Bodige ◽  
Parameshwar Ravula ◽  
Kali Charan Gulipalli ◽  
Srinivas Endoori ◽  
Purna Koteswara Rao Cherukumalli ◽  
...  
Keyword(s):  
In Silico ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
Design Synthesis ◽  
In Silico Docking

Novel Cinnamic Acid Derivatives as Potential PPARδ Agonists for Metabolic Syndrome: Design, Synthesis, Evaluation and Docking Studies

2020 ◽  
Vol 17 (3) ◽  
pp. 338-347
Author(s):  
Ajay Chauhan ◽  
Ajmer S. Grewal ◽  
Deepti Pandita ◽  
Viney Lather
Keyword(s):  
Cinnamic Acid ◽  
In Silico ◽  
Metabolic Disorders ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Cinnamic Acid Derivatives ◽  
In Silico Docking ◽  
Study Results

Background: Peroxisome proliferator-activated receptor (PPAR) δ is expressed universally in the entire tissues, particularly in those concerned with the lipid metabolism. PPAR δ stimulation alters body’s energy fuel preference to fat from glucose and shows up as an emerging pharmacological target for the treatment of metabolic disorders. Methods: A new series of cinnamic acid derivatives was synthesized and evaluated for the antidiabetic and antiinflammatory activities in the animal models followed by in silico docking studies to determine the binding interactions for the best fit conformations in the binding site of the PPARδ protein. Results: Amongst the synthesized molecules, compound 3 showed higher antidiabetic activity in oral glucose tolerance test and compound 1 showed higher antiinflammatory activity in the carrageenan induced rat paw oedema method. The in vivo study results were supported by the similar in silico molecular docking results. Most of the synthesized derivatives showed drug likeness as depicted via Lipinski’s rule of 5. Conclusion: These molecules can serve as the early hit molecules for the discovery of safe, effective and bioavailable PPARδ agonists for the potential treatment of various metabolic disorders.</P>

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