title: Ligand-based virtual screening, parallel solution-phase and microwave-assisted synthesis as tools to identify and synthesize new inhibitors of mycobacterium tuberculosis.
abstract: In an attempt to identify new inhibitors of the growth of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, a procedure for the generation, design, and screening of a ligand-based virtual library was applied. This used both an in silico protocol centered on a recursive partitioning (RP) model described herein, and a pharmacophoric model for antitubercular agents previously generated by our research group. Two candidates emerged from databases of commercially available compounds, both characterized by a minimum inhibitory concentration (MIC) of 25 microg mL(-1). Based on these compounds, two series of derivatives were synthesized by both parallel solution-phase and microwave-assisted synthesis, leading to enhanced antimycobacterial activity. During both the design and synthesis, attention was focused on the efficient allocation of available resources with the aim of reducing the overall costs associated with calculation and synthesis.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università Degli Studi di Siena, Via Alcide de Gasperi 2, 53100 Siena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Matteo
authors.initials: M
authors.lastname: Magnani
authors.forename: Daniele
authors.initials: D
authors.lastname: Castagnolo
authors.forename: Laura
authors.initials: L
authors.lastname: Passalacqua
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
authors.forename: Federico
authors.initials: F
authors.lastname: Corelli
authors.forename: Manuela
authors.initials: M
authors.lastname: Saddi
authors.forename: Delia
authors.initials: D
authors.lastname: Deidda
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Logu
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001185:Artificial Intelligence; D019295:Computational Biology; D003198:Computer Simulation; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D015269:Mycobacterium avium Complex / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012996:Solutions
chemical_list: D000995:Antitubercular Agents; D008024:Ligands; D012996:Solutions