Mycobacterium tuberculosis thiosemicarbazones

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

The antimicrobial activity of thiosemicarbazones against Mycobacterium tuberculosis in vitro was first reported by Domagk et al. [28] and later confirmed in vivo [29]. Screening revealed that only certain substituted be-nzaldehyde and heterocyclic thiosemicarbazones possess antitubercular activity [30-32]. The most widely used is p-acetamidobenzaldehyde thiosemicarbazone (trivial name = thiacetazone), 1. 

Since the causative organism of leprosy, one of the world s six major diseases, Mycobacterium leprae, is closely related to Mycobacterium tuberculosis, thio-semicarbazones have also been used as second-line drugs in the chemotherapy of leprosy [38]. The most widely used in leprosy treatment has been thiacetazone, and structure-activity relationships for it are similar to those observed for antitubercular thiosemicarbazones [39, 40]. 

It is chemically related to nicotinamide and thiosemicarbazone. It is bactericidal. It is effective against Mycobacterium tuberculosis resistant to INH and streptomycin. It is converted to pyrazinoic acid (active... 

Thiosemicarbazones of starch dialdehyde and thiosemicarbazones and condensation products of starch dialdehyde with isoniazid were evaluated for their antituberculostatic activity, and showed positive effects with mice that were intravenously infected with Mycobacterium tuberculosis. 613-614-617-2627-2629 These results were contradicted by other authors615,616 who showed acceleration of M. tuberculosis growth in vitro in contact with starch dialdehyde thiosemicar-bazone. A potential application of this compound was suggested in tuberculosis taxonomy. 

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