TY - JOUR
T1 - New fluoroquinolones/nitric oxide donor hybrids
T2 - design, synthesis and antitubercular activity
AU - Aziz, Hossameldin A.
AU - Moustafa, Gamal A.I.
AU - Abbas, Samar H.
AU - Hauk, Glenn
AU - Siva Krishna, Vagolu
AU - Sriram, Dharmarajan
AU - Berger, James M.
AU - Abuo-Rahma, Gamal El Din A.
N1 - Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - New nitric oxide (NO) donating fluoroquinolones/nitrate ester hybrids were prepared and their structures were characterized by various spectroscopic and analytical tools. The release of NO from the prepared nitrate esters was measured using the modified Griess colorimetric method. Evaluation of antitubercular activity showed that most of tested compounds exhibited comparable or higher activity than the parent fluoroquinolones. Compounds 2b, 3a, 4a, 5a, and 2d showed better activity than ciprofloxacin. Nevertheless, none of the new compounds were superior to the parent fluoroquinolones in terms of DNA cleavage stimulation in mycobacteria. The additional growth inhibition effect that is distinct from gyrase poisoning may be due to release of NO or enhancement of lipophilicity. These data are augmented by docking results where the docked compounds did not exert additional significant bindings over the parent fluoroquinolones.
AB - New nitric oxide (NO) donating fluoroquinolones/nitrate ester hybrids were prepared and their structures were characterized by various spectroscopic and analytical tools. The release of NO from the prepared nitrate esters was measured using the modified Griess colorimetric method. Evaluation of antitubercular activity showed that most of tested compounds exhibited comparable or higher activity than the parent fluoroquinolones. Compounds 2b, 3a, 4a, 5a, and 2d showed better activity than ciprofloxacin. Nevertheless, none of the new compounds were superior to the parent fluoroquinolones in terms of DNA cleavage stimulation in mycobacteria. The additional growth inhibition effect that is distinct from gyrase poisoning may be due to release of NO or enhancement of lipophilicity. These data are augmented by docking results where the docked compounds did not exert additional significant bindings over the parent fluoroquinolones.
KW - Antitubercular
KW - Cleavable DNA complex
KW - Fluoroquinolones
KW - Molecular docking
KW - Nitric oxide (NO)
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U2 - 10.1007/s00044-019-02372-y
DO - 10.1007/s00044-019-02372-y
M3 - Article
AN - SCOPUS:85067240343
SN - 1054-2523
VL - 28
SP - 1272
EP - 1283
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 8
ER -