Drugs used in the treatment of tuberculosis and leprosy

Onakpoya, Igho

doi:10.1016/bs.seda.2022.08.011

Cited by 3 publications

(1 citation statement)

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“…It is estimated that approximately 30% of the global population are carriers of this bacterium, and every year, the World Health Organization reports numerous diseases and deaths caused by its infection [ 2 ]. The tuberculosis treatment process is very demanding for patients, not only because of the extended duration of therapy but also because of the side effects that occur after taking tuberculosis drugs, such as nausea, hearing loss, or hepatotoxicity [ 3 , 4 ]. Immunocompromised patients, including those using immunosuppressive drugs or who are HIV-positive, are at higher risk of tuberculosis [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity of Piperidinothiosemicarbazones Derived from Aminoazinecarbonitriles

Ziembicka,

Gobis,

Szczesio

et al. 2023

Pharmaceuticals

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To investigate how structural modifications affect tuberculostatic potency, we synthesized seven new piperidinothiosemicrabazone derivatives 8–14, in which three of them had a pyrazine ring replacing the pyridine ring. Derivatives 8–9 and 13–14 exhibited significant activity against the standard strain (minimum inhibitory concentration (MIC) 2–4 μg/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5–4 μg/mL). Additionally, the effects of compounds 8–9 were entirely selective (MIC toward other microorganisms ≥ 1000 μg/mL) and non-toxic (IC50 to HaCaT cells 5.8 to >50 μg/mL). The antimycobacterial activity of pyrazine derivatives 11–12 was negligible (MIC 256 to >500 μg/mL), indicating that replacing the aromatic ring was generally not a promising line of research in this case. The zwitterionic structure of compound 11 was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion (ADME) calculations showed that all compounds, except 11, could be considered for testing as future drugs. An analysis of the structure–activity relationship was carried out, indicating that the higher basicity of the substituent located at the heteroaromatic ring might be of particular importance for the antituberculous activity of the tested groups of compounds.

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Section: Introductionmentioning

confidence: 99%