Pharmacophoric model building for antitubercular activity of the individual Schiff bases of small combinatorial library
| Autor: | Hoda Y. Hassan, Wesam S. Abdel-Aal, Tarek Aboul-Fadl, Adel F. Youssef |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Antitubercular Agents Hydrazone Models Biological Metal Drug Discovery Combinatorial Chemistry Techniques Computer Simulation Schiff Bases Antibacterial agent Pharmacology chemistry.chemical_classification Molecular Structure Hydrogen bond Organic Chemistry Aromaticity General Medicine Mycobacterium tuberculosis chemistry visual_art Drug Design Lipophilicity visual_art.visual_art_medium Pharmacophore |
| Zdroj: | European journal of medicinal chemistry. 45(3) |
| ISSN: | 1768-3254 |
| Popis: | Synthesis and evaluation of anti-TB activity of individual compounds of Schiff bases combinatorial library were done against Mycobacterium tuberculosis H 37 Rv at a single concentration of 6.25 μg/mL according to the protocol of TAACF. Compounds 2C and 3D produced 99% inhibitory activity on the investigated organism, while the other tested compounds showed lower activity ranging from 35 to 84%. It was found that there are no relation between the anti-TB activity of the tested compounds and their lipophilicity expressed by C log P of these compounds. A 3D pharmacophoric model has been generated by Molecular Operating Environment (MOE) using a training set of 10 reported anti-TB compounds and testing the synthesized compounds ( 1A , 1B , 1D , 1E , 2C , 3A , 3C , 3D , 3E and 4A – 4E ). The generated pharmacophoric features include, F1 : hydrogen bond donors (Don), F2 : aromatic rings (Aro), F3 : hydrogen bond acceptors (Acc)/metal ligator (ML), F4 : Aro/hydrophobic (Hyd). In all hit set, it was found that the amidic nitrogen CONH–N C fitted the region of the Don, F1 , while the amidic carbonyl group fitted the region of the Acc/ML, F3 . The distances bridging F1 to F2 , F3 and F4 were essential for anti-TB activity in the developed pharmacophore model, as it was confirmed from model validation procedure. |
| Databáze: | OpenAIRE |
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