Background: Heterocyclic compounds have attracted much attention to synthetic and medicinal
chemists because of their biological activities especially for tuberculosis (TB).Moreover, fatal forms of TB (including
tuberculous meningitis) have led to search for new structural anti-TB agents. So, we have built a scaffold
using imidazo[1,2-b]pyridazine, piperazine and morpholine moieties, which are widely used in the inhibition
of resistant strains of various organisms.
Objective: The aim was to synthesise 6-morpholino-3-(piperazine-1-yl)imidazo[1,2-b]pyridazine containing
amide and sulphonamide derivatives and evaluate their antimycobacterial and locomotor activities.
Methods: The novel imidazo[1,2-b]pyridazine, piperazine and morpholine scaffolds have been synthesized in
seven steps. All the synthesized compounds (8a-j) were screened for in vitro antimycobacterial activity against
M.tb H37Rv strains using the MABA, in vivo locomotor activity by using photoactometer and rotarod apparatus.
Results: All the synthesized imidazo[1,2-b]pyridazine analogues were characterized by 1H NMR, 13C NMR
and ESI-MS. The compounds 8h and 8j exhibited potent in vitro anti-TB activity at 1.6 µg/mL concentration.
Based on the structural and in vitro studies, we had related SAR of 8a-j. Overall, the amide derivatives showed
better antitubercular activity than sulphonamide derivatives, which might be due to easy hydrogen bond formation.
Moreover, all the derivatives showed significant CNS depressant action lacking neurotoxicity that indicates
that the compounds 8a-j have strong lipophilic nature.
Conclusion: The presence of novel structure, lipophilicity and non-toxic nature provide impetus for compounds
8a-j in the diagnosis of TB and tuberculous meningitis along with first line anti-TB drugs.