Design, synthesis and biological evaluation of (Quinazoline 4-yloxy)acetamide and (4-oxoquinazoline-3(4H)-yl)acetamide derivatives as inhibitors of Mycobacterium tuberculosis bd oxidase

Cytochrome bd oxidase: an emerging anti-tubercular drug target

“…19). 55 Total cellular ATP depletion assay of 10 and 11 in monotherapy and combination therapy with Q203 indicated that an appreciable reduction of ATP level is produced only in combination with Q203 (Fig. 20).…”

“…53 Kumar et al reported the design and synthesis of two series of compounds, (quinazoline 4-yloxy)acetamide derivatives and (4-oxoquinazoline-3(4H)-yl)acetamide derivatives as cyt-bd oxidase inhibitors and further conducted multiple virtual screening and biological studies. 55 They adopted the scaffold hopping technique on three previously reported anti-TB compounds: 2, 1, and 2-(quinolin-4-yloxy) acetamide based derivative 40,50,56 and designed the first series of compounds by linking the quinazoline moiety of 2 with the acetamide chain of 2-(quinolin-4-yloxy)acetamide class of compounds, while second series of compounds were…”

“…16.) 55 Twenty-nine synthesized compounds of both series were initially screened against two strains of Mtb, wild-type Mtb H37Rv and the deletion-mutated strain of Mtb, lacking the cytochrome b (QcrB) subunit of bc 1 complex. Of these, only two compounds had inhibitory potential at a concentration below 32 μM.…”

“…Due to the compensatory function of the cyt bcc 1 /aa 3 super complex, such high values were reported. 55 When the two lead compounds were tested individually for synergistic response with Q203, only 11 showed synergism (Fig. 18).…”

“…18). 55 To evaluate inhibitory potential against cyt-bd, the authors explored the bactericidal response of 10 and 11 under hypoxic conditions to non-replicating TB strains, and both the compounds produced strong bactericidal response resulting in ∼1.9 log 10 reduction at 32 μM concentration. In conjunction with Q203, 10 and 11 showed an approximate four times enhancement in potency (Fig.…”