title: Planarity of benzoyldithiocarbazate tuberculostatics. II. Diesters of benzoyldithiocarbazic acid.
abstract: The emergence of drug-resistant strains of Mycobacterium tuberculosis has intensified efforts to identify new lead tuberculostatics. Our earlier studies concluded that the planarity of a molecule correlates well with its tuberculostatic activity. According to our hypothesis, only derivatives whose molecules are capable of adopting a planar conformation may show tuberculostatic activity. The structures of three new potentially tuberculostatic compounds, namely N'-[bis(methylsulfanyl)methylidene]-N-methyl-4-nitrobenzohydrazide (denoted G1), C11H13N3O3S2, N'-[bis(benzylsulfanyl)methylidene]-N-methyl-4-nitrobenzohydrazide (denoted G2), C23H21N3O3S2, and N'-[(benzylsulfanyl)(methylsulfanyl)methylidene]-4-nitrobenzohydrazide (denoted G3), C16H15N3O3S2, were determined by X-ray diffraction. The significant distortion from planarity caused by the methyl substituent at the N atom of the hydrazide group or the NO2 substituent in the aromatic ring leads to the loss of tuberculostatic activity for G1, G2 and G4 {systematic name: N'-[bis(methylsulfanyl)methylidene]-2-nitrobenzohydrazide}. A similar effect is observed when there are large substituents at the S atoms (G2 and G3).
authors.affiliation: Institute of General and Ecological Chemistry, Department of Chemistry, Lodz University of Technology, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szczesio
authors.affiliation: Institute of General and Ecological Chemistry, Department of Chemistry, Lodz University of Technology, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Olczak
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gobis
authors.affiliation: Institute of General and Ecological Chemistry, Department of Chemistry, Lodz University of Technology, Poland.
authors.forename: Ida
authors.initials: I
authors.lastname: Mazerant
authors.affiliation: Institute of General and Ecological Chemistry, Department of Chemistry, Lodz University of Technology, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kałużyńska
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Foks
authors.affiliation: Institute of General and Ecological Chemistry, Department of Chemistry, Lodz University of Technology, Poland.
authors.forename: Marek L
authors.initials: ML
authors.lastname: Główka
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000187:drug effects*; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D006834:Hydrazines; C000608057:N'-((benzylsulfanyl)(methylsulfanyl)methylidene)-4-nitrobenzohydrazide; C000608056:N'-(bis(benzylsulfanyl)methylidene)-N-methyl-4-nitrobenzohydrazide; C000608055:N'-(bis(methylsulfanyl)methylidene)-N-methyl-4-nitrobenzohydrazide; D009574:Nitro Compounds
keywords: DFT analysis; Mycobacterium tuberculosis; ab initio calculations; benzohydrazides; crystal structure; drug resistance; tuberculostatic activity