6533b824fe1ef96bd12801cb

RESEARCH PRODUCT

New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method

Remedios GunaCarlos Fuertes MuñozRamón García-domenechJesus-vicente De Julián-ortizJorge GalvezRafael BorrásÁNgeles García-garcía

subject

PharmacologyMicrobiology (medical)Virtual screeningQuantitative structure–activity relationshipbiologymedicine.drug_classBroth microdilutionQuantitative Structure-Activity RelationshipMicrobial Sensitivity TestsComputational biologyMycobacterium avium Complexbiology.organism_classificationLinear discriminant analysisAntimycobacterialModels BiologicalIn vitroAnti-Bacterial AgentsMicrobiologyInfectious DiseasesDrug DesignmedicinePharmacology (medical)Mycobacterium avium complexMolecular topology

description

Objectives: In order to select new drugs and to predict their in vitro activity against Mycobacterium avium complex (MAC), new quantitative structure-activity relationship (QSAR) models were developed. Methods: The activities against MAC of 29 structurally heterogeneous drugs were examined by means of linear discriminant analysis (LDA) and multilinear regression analysis (MLRA) by using topological indices (TI) as structural descriptors. In vitro antimycobacterial activities were determined by a broth microdilution method with 7H9 medium. Results: The topological model obtained successfully classifies over 80% of compounds as active or inactive; consequently, it was applied in the search for new molecules active against MAC. From among the selected candidates demonstrating in vitro activity, aflatoxin B1, benzalkonium chloride and pentamidine stand out, with MIC 50 s between 4 and 32 mg/L. Conclusion: The method described in this work is able to select molecules active against MAC.

yearjournalcountryeditionlanguage
2003-12-04Journal of Antimicrobial Chemotherapy
https://doi.org/10.1093/jac/dkh014