Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work reveals our efforts to continue identifying new active compounds against neglected diseases, such as malaria and tuberculosis. We took several 3-arylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivative activity results from the reference literature and established useful quantitative structure-activity relationships. We hoped that the development of in silico models would broaden our knowledge regarding the overwhelming problem of drug resistance to both illnesses. The optimized molecular structures of 60 compounds were represented by 1497 DRAGON-type descriptors and subjected to linear regression analyses; the quantitative structure-activity relationships resulted predictive when searching for new active compounds. We obtained a rational guide for the proposal of new candidate structures whose activities still remain unknown.
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PMID:Exploring 3-arylquinoxaline-2-carbonitrile 1,4-di-N-oxides activities against neglected diseases with QSAR. 2049 46

The aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds are the most important class of Plasmodium falciparum carbonic anhydrase (pfCA) inhibitors. Sulfonamide inhibitors of the protozoan CAs may have potential for the development of novel therapies of human malaria. I have attempted to build QSAR models using the OMEGA, MOPAC, PRECLAV, DRAGON and BROOD software to explore the correlations between the calculated molecular descriptors on the pool of 27 compounds and their experimental pfCA inhibitory activities. The novelty of this work consists in not only exploring the structural attributes of bioactive molecules but in predicting in silico the structures of new compounds which may show antimalarial activity. The analogs of the lead molecule are generated by replacing selected fragments that have similar shape and electrostatics. The various pharmacokinetic evaluations and synthetic accessibility test were also carried out to search more suitable compounds. The molecules of the prediction set include many molecules having high computed activity compared to the reported such derivatives.
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PMID:Computational design and chemometric QSAR modeling of Plasmodium falciparum carbonic anhydrase inhibitors. 2546 3