title: The structure-antituberculosis activity relationships study in a series of 5-aryl-2-thio-1,3,4-oxadiazole derivatives.
abstract: A series of 82 5-aryl-2-thio-1,3,4-oxadiazole derivatives were screened for their anti-mycobacterial activities against Mycobacterium tuberculosis H37Rv. The synthesized compounds 30-37 appeared to be the most active derivatives exhibiting more than 90% inhibition of mycobacterial growth at 12.5 μg/mL. Structure-activity relationships study was performed for the given series by using the electronic-topological method combined with neural networks (ETM-NN). A system for the anti-mycobacterial activity prediction was developed as the result of training associative neural network (ASNN) with weights calculated from projections of a compound and each pharmacophoric fragment found on the elements of the Kohonen's self-organizing maps (SOMs). From the detailed analysis of all compounds under study, the necessary requirements for a compound to possess antituberculosis activity have been formulated. The analysis has shown that any requirement's violation for a molecule implies a considerable decrease or even complete loss of its activity. Molecular docking studies of the compounds allowed shedding light on the binding mode of these novel anti-mycobacterial inhibitors.
authors: Institute of Chemistry, Academy of Sciences of Moldova, Chisinau, Republic of Moldova. flmacaev@cc.acad.md
authors: Fliur
authors: F
authors: Macaev
authors: Zinaida
authors: Z
authors: Ribkovskaia
authors: Serghei
authors: S
authors: Pogrebnoi
authors: Veaceslav
authors: V
authors: Boldescu
authors: Ghenadie
authors: G
authors: Rusu
authors: Nathaly
authors: N
authors: Shvets
authors: Anatholy
authors: A
authors: Dimoglo
authors: Athina
authors: A
authors: Geronikaki
authors: Robert
authors: R
authors: Reynolds
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D010069:Oxadiazoles