Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid carbohydrazide
Bin-Jubair, Fayzah A.S. . 2010
Tuberculosis (TB) remains among the world’s great public health challenges.Worldwide resurgence of TB
is due to two major problems: the AIDS epidemic, which started in the mid-1980s, and the outbreak of
multidrug resistant (MDR) TB. Thus, there is an urgent need for anti-TB drugs with enhanced activity
against MDR strains. In recent years, Schiff bases of 1H-indole-2,3-diones are reported to exhibit anti-TB
activity. On the other hand, several quinolone antibacterial agents have been examined as inhibitors of
TB, as well as other mycobacterial infections. Accordingly, the current work involved design and
synthesis of Schiff bases of nalidixic acid carbohydrazide and isatin derivatives (5,6aef and 7,8aec).
Structures of the synthesized derivatives were confirmed on the bases of spectral methods of analyses.
Anti-TB activity of the synthesized derivatives was investigated against four Mycobacterium strains:
Mycobacterium intercellulari, Mycobacterium xenopi, Mycobacterium cheleneo and Mycobacterium smegmatis.
Modest anti-TB activity was observed within the investigated compounds, however, compound 5f
revealed potent anti-TB activity with MIC 0.625 mg/ml, which is 20 times greater than the reference drug
isoniazid, INH, (MIC ¼ 12.5 mg/ml). A hypothetical pharmacophore model was built using Molecular
Operating Environment (MOE) program and 10 compounds structurally related to the synthesized ones
with reported anti-TB activity. The Pharmacophoric model built revealed the necessity of the following
pharmacophoric features for anti-TB activity: aromatic center, hydrogen bond acceptor/metal ligator
center, hydrogen bond donor center and aromatic center/hydrophobic area. Theses features were
consistent with the found anti-TB activity of the tested compounds.
The present invention relates to an isatin derivative having the formula (I),
a medicament for treatment of tuberculoses containing that isatin derivative as Well as a method for preparing…
Tuberculosis (TB) remains among the world’s great public health challenges.Worldwide resurgence of TB
is due to two major problems: the AIDS epidemic, which started in the mid-1980s, and…