Table 1.

Activity of various heterocyclic scaffolds (1–14) against replicating Mtb H₃₇Rv in various media, against non-replicating Mtb —LORA and cytotoxicity in VERO cells

Compound	Mol. Wt.	Calc. ClogP*	MIC mean ±/− SD (μM) [MIC range] against replicating Mtb in medium:			LORA (μM)	VERO IC50 (μM)
			GAS	GAST	7H12
1	281.31	2.76	4.9 ± 1.7 [2.9–6.2]	4.4 [5.7–3.7]	16.6 ± 11.1 [3.8–24.0]	63	>128
2	279.29	3.47	5.7± 2.3 [0.5–7.9]	0.49 [<1–0.5]	3.9± 1.0 [3.0–5.0]	37	121
3	278.31	3.70	>65 [23.1–>128]	59	>40 [19.5–>50]	NT	NT
4	297.37	2.94	12.9± 4.8 [9.1–18.3]	3.5	11.6± 5.1 [7.7–17.4]	NT	>128
5	295.36	4.10	6.0± 4.0 [1.5–8.5]	6.2	7.2± 3.0 [4.0–9.8]	NT	>128
6	278.31	4.54	3.5± 1.4 [1.8–4.3]	>64	>38 [15.0–>50]	NT	>128
7	279.29	4.30	2.2± 1.0 [1.1–2.9]	NT	0.8± 0.01 [0.7–0.8]	28.0± 1.3 [26.9–29.4]	>50
8	319.35	4.71	1.9±0.6 [1.5–2.5]	NT	9.5±3.2 [5.8–11.9]	NT	NT
9	342.39	5.89	<0.195	NT	<0.195	21.7± 0.8 [21.1–22.6]	>50
10	341.41	5.30	0.6±0.1 [0.5–0.7]	NT	2.9±0.1 [2.8–3.0]	>50	>50
11	280.32	4.07	<0.195	NT	<0.195	34.8± 3.4 [31.3–38.2]	>50
12	279.34	3.60	0.7 [0.4–1.1]	2.0 [<0.5–3.4]	2.3 [1.9–2.7]	54	>128
13	267.28	2.40	2.3±0.5 [1.7–2.7]	NT	4.7±1.1 [3.2–5.2]	NT	>50
14	295.34	3.40	1.1±0.3 [0.9–1.4]	NT	5.3±0.5 [5.0–5.9]	NT	>50
Isoniazid (INH)	137.14	−0.67	0.22±0.01 [0.23–0.22]	NT	0.37±0.12 [0.23–0.46]	>512	>128
Rifampin (RMP)	822.94	6.04	0.09±0.01 [0.08–0.1]	0.2	0.04±0.01 [0.03–0.05]	2.6	113

^*Calculated ClogP by ChemDraw version 12.0; SD = standard deviation; MIC = Minimum Inhibitory Concentration required to inhibit the growth of 90% of organisms; NT = Not tested; GAS = Glycerol-alanine-salts media; GAST = Iron deficient glycerol-alanine-salts with Tween 80 media; 7H12 = 7H9 broth base media with BSA, casein hydrolysate, catalase, palmitic acid; LORA = Low oxygen recovery assay using the Mtb H₃₇Rv luxAB luminescence strain; VERO = African green monkey kidney cell line to evaluate toxicity. Values reported are the average of three individual measurements.