Microwave assisted synthesis, antimalarial screening and structure–activity-relationship exploration of some phenylthiazolyl-triazine derivatives against dihydrofolate reductase

2016 ◽  
Vol 25 (12) ◽  
pp. 2916-2923 ◽  
Author(s):  
Supriya Sahu ◽  
Surajit K. Ghosh ◽  
Anirban Ghoshal ◽  
Junmoni Kalita ◽  
Prashant Gahtori ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
Structure Activity ◽  
Triazine Derivatives

scholarly journals Design, microwave-assisted synthesis, bioactivity and SAR of novel substituted 2-phenyl-2-cyclohexanedione enol ester derivatives

RSC Advances ◽  
2018 ◽  
Vol 8 (35) ◽  
pp. 19883-19893 ◽  
Author(s):  
Fei Ye ◽  
Peng Ma ◽  
Yue Zhai ◽  
Fei Yang ◽  
Shuang Gao ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
Structure Activity ◽  
Herbicide Safeners ◽  
Enol Ester

Based on the structure–activity relationship and active substructure combination, a novel class of substituted 2-phenyl-2-cyclohexanedione enol ester derivatives was designed for use as potential herbicide safeners.

Microwave-assisted synthesis of new sulfonyl hydrazones, screening of biological activities and investigation of structure–activity relationship

2016 ◽  
Vol 25 (8) ◽  
pp. 1590-1607 ◽  
Author(s):  
Nurcan Karaman ◽  
Emine Elçin Oruç-Emre ◽  
Yusuf Sıcak ◽  
Berna Çatıkkaş ◽  
Ayşegül Karaküçük-İyidoğan ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
Structure Activity

scholarly journals Multitarget, Selective Compound Design Yields Picomolar Inhibitors of a Kinetoplastid Pteridine Reductase 1

2020 ◽  
Author(s):  
Ina Poehner ◽  
Antonio Quotadamo ◽  
Joanna Panecka-Hofman ◽  
Rosaria Luciani ◽  
Matteo Santucci ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Dihydrofolate Reductase ◽  
Multidisciplinary Approach ◽  
Microwave Assisted Synthesis ◽  
Crystallographic Structure ◽  
Computational Docking ◽  
Design And Optimization ◽  
Microwave Assisted ◽  
Structure Activity ◽  
Further Development

The optimization of compounds with multiple targets in the drug discovery cycle is a difficult multidimensional problem. Here, we present a systematic, multidisciplinary approach to the development of selective anti-parasitic compounds. Efficient microwave-assisted synthesis of pteridines along with iterations of crystallographic structure determination were used to validate computational docking predictions and support derivation of a structure-activity relationship for multitarget inhibition. This approach yielded compounds showing picomolar inhibition of <i>T. brucei</i> pteridine reductase 1 (PTR1), nanomolar inhibition of <i>L. major</i> PTR1, along with selective submicromolar inhibition of parasitic dihydrofolate reductase (DHFR). Moreover, by combining design for polypharmacology with a property-based on-parasite optimization, we found three compounds that exhibited micromolar EC<sub>50</sub> values against <i>T. brucei brucei</i>, whilst retaining their target inhibition. Our results provide a basis for the further development of pteridine-based compounds and we expect our multitarget approach to be generally applicable to the design and optimization of anti-infective agents.<br>

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