Anthranilic amide and imidazobenzothiadiazole compounds disruptMycobacterium tuberculosismembrane potential

Abstract

Compounds 1 and 2 disrupt M. tuberculosis membrane potential and demonstrate bactericidal activity against non-replicating M. tuberculosis in pH 4.5 buffer.

Targeting Mycobacterium tuberculosis pH-driven adaptation

“…Furthermore, its activity against replicating and non-replicating Mtb suggests that nitazoxanide has a potentially novel mechanism of action and multiple targets [ 87 92 ]. Compound 16 disrupts Mtb membrane potential in a pH-dependent manner, and has been proposed as a new tool to evaluate Mtb membrane potential disruption at acidic pH because it exhibits greater depolarization than CCCP compared to a DMSO control [ 93 ]. Monensin is another membrane potential disruptor that also acts as an ionophore ( Table 1 ) [ 71 ].…”

Synthetic approaches to potent heterocyclic inhibitors of tuberculosis: A decade review

“…However, increase in the alkyl chain length (n = 4, n = 6) and the induction of the morpholine ring resulted in the improvement of activity indicating a 6.25 μM MIC value of compounds 122a, 122b, and 122c with lesser cytotoxicity. Parish and his group in 2019 reported the membrane potential disruption of M. tb by imidazobenzathiazole analogs (Figure 11) (Smith et al, 2019). Mensuration of membrane potential toward human liver cells in HepG2 was performed by the conventional method where 50,000 cells were plated per well in 96-well plates.…”

“…Parish and his group in 2019 reported the membrane potential disruption of M. tb by imidazobenzathiazole analogs ( Figure 11 ) ( Smith et al, 2019 ). Mensuration of membrane potential toward human liver cells in HepG2 was performed by the conventional method where 50,000 cells were plated per well in 96-well plates.…”

“… M. tb membrane potential disruption at pH 6.8 by benzothiadiazole analogs. Reproduced from Smith et al, 2019 , with permission from Royal Society of Chemistry, Copyright 2019. …”