title: The structure--antituberculosis activity relationships study in a series of 5-(4-aminophenyl)-4-substituted-2,4-dihydro-3h-1,2,4-triazole-3-thione derivatives. A combined electronic-topological and neural networks approach.
abstract: Antituberculosis activity of several 5-(4-aminophenyl)-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones (1-9) and their thiourea derivatives (10-31) were screened for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Of the synthesized compounds, 10-12, 30 were the most active derivatives exhibiting more than 90 % inhibition of mycobacterial growth at 12.5 microg/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 of prognosis was developed as the result of training associative neural network (ASNN) using weights of pharmacophoric fragments as descriptors. Descriptors were calculated by the projection of ETM compound and pharmacophoric fragments on the elements of Kohonen's self-organizing maps (SOM). From the detailed analysis of all compounds under study, the necessary requirements for a compound to possess antituberculosis activity were formulated. The analysis have shown that any requirements violation for a molecule implies a considerable decrease or even complete loss of its activity.
authors.affiliation: Gebze Institute of Technology, PK-141, Gebze/Kocaeli, 41400, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Kandemirli
authors.forename: Nathali
authors.initials: N
authors.lastname: Shvets
authors.forename: Seda
authors.initials: S
authors.lastname: Unsalan
authors.forename: Ilkay
authors.initials: I
authors.lastname: Küçükgüzel
authors.forename: Sevim
authors.initials: S
authors.lastname: Rollas
authors.forename: Vasyl
authors.initials: V
authors.lastname: Kovalishyn
authors.forename: Anatholy
authors.initials: A
authors.lastname: Dimoglo
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004581:Electronics; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D016571:Neural Networks, Computer; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D014230:Triazoles