Screening for In Vitro Antimycobacterial Activity and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Study of 4-(arylamino)coumarin Derivatives
| Autor: | Kinnari Dholariya, Alpesh Parecha, Vipul Vora, Anamik Shah, Gautam Patel, Karia Denish, Bhavik Desai, Evans C. Coutinho, Raju Loriya, Atul Manvar, Kuldip Upadhyay, Mushtaque S. Shaikh, Vijay Virsdoia |
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| Rok vydání: | 2010 |
| Předmět: |
Pharmacology
Quantitative structure–activity relationship Chemistry medicine.drug_class Stereochemistry Chemical structure Organic Chemistry Antimycobacterial Coumarin Biochemistry Combinatorial chemistry In vitro chemistry.chemical_compound Minimum inhibitory concentration Drug Discovery Mycobacterium tuberculosis H37Rv medicine Molecular Medicine Molecule |
| Zdroj: | Chemical Biology & Drug Design. 76:412-424 |
| ISSN: | 1747-0277 |
| DOI: | 10.1111/j.1747-0285.2010.00997.x |
| Popis: | The resurgence of tuberculosis and the emergence of multidrug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We have synthesized a small library of 50 analogues of 4-(arylamino)coumarins with various aromatic amines at the C4- position of the coumarin scaffold. The compounds were evaluated for antimycobacterial activity against Mycobacterium tuberculosis H37Rv with rifampicin as the standard. Of the molecules synthesized, compound 9 was found to be most potent with a minimum inhibitory concentration >6.25 μg/mL for 100% inhibition. In an effort to develop new and more effective molecules in this series, the relationship between structure and activity was investigated by comparative molecular field analysis. Various models were generated using comparative molecular field analysis alone and comparative molecular field analysis plus a hydropathy field (HINT). In all, eight models were generated with atom-fit and field-fit alignment strategies. The comparative molecular field analysis models (Models 3a and 4a) based on field-fit alignment were the best with statistically good correlation coefficients (r2) and cross-validated q2. The values of r2pred for the validation set were 0.469 and 0.516. Based on the comparative molecular field analysis contours, some insights into the structure–activity relationship of the compounds could be gained. |
| Databáze: | OpenAIRE |
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