Author/Authors :
Esfahanizadeh, Marjan Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran - Central Research Laboratories - Shahid Beheshti University of Medical Sciences, Tehran , Omidi, Koroush Central Research Laboratories - Shahid Beheshti University of Medical Sciences, Tehran , Kauffman, Joel Department of Chemistry and Biochemistry - University of the Sciences in Philadelphia - Philadelphia - PA, USA , Gudarzi, Ali Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran , Shahraki Zahedani, Shahram Department of Microbiology - School of Medicine - Zahedan University of Medical Sciences, Zahedan , Amidi, Salimeh Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran , Kobarfard, Farzad Phytochemistry Research Center - Shahid Beheshti University of Medical Sciences, Tehran - Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran
Abstract :
Treatment of tuberculosis (TB) and the discovery of effective new anti-tubercular drugs are among the most urgent priorities in health organizations all over the world. In the present study, fluorinated analogs of some of the most important anti-TB agents such as p-aminosalicylic acid (PAS), thiacetazone and pyrazinamide were synthesized and tested against TB. The fluorinated analog of thiacetazone was 20 times more potent than the parent compound against M.tuberculosis H37-RV, while the fluorinated p-aminosalicylic acid (PAS) was almost three times less potent than PAS. A few other halogenated analogs of thioacetazone were also synthesized
and subjected to anti-M.tuberculosis screening tests. The best halogen substituent was found to be fluorine which has the smallest size from one hand and the strongest electronegativity from the other hand among the halogen atoms. Fluorine therefore could be considered as a golden substituent to improve the anti-M.tuberculosis activity of thioacetazone.
Keywords :
Fluorinated analogs , Anti-tuberculosis drugs , Pyrazinamide , PAS , Thiacetazone
