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. Author manuscript; available in PMC: 2023 Oct 18.
Published in final edited form as: Eur J Med Chem. 2022 Nov 11;245(Pt 2):114916. doi: 10.1016/j.ejmech.2022.114916

Table 2.

Antitubercular activity, cytotoxicity and metabolic stability of compounds synthesized

graphic file with name nihms-1937709-t0014.jpg
Cmpd Ring A R R1 X MIC90a μg/mL (μM)
MtbH37Rv 		MIC90b μg/mL (μM)
M. Marinum 		IC50c μg/mL
(μM)		 HLM stabilityd (min)
3 Phenyl H 4-CH3 S 1.0(2.7) 0.5(1.3) 88(234) t1/2 = 35 ± 1
4 2-Pyridine H 4-CH3 S 0.5(1.3) 0.5(1.3) 22.1(59) t1/2 = 16 ± 1
9a Phenyl 4-F 4-CH3 S 1.0(2.5) nde 46.8(118) nd
10a Phenyl 3-F 4-CH3 S 2.5(6.3) nd nd nd
11a Phenyl 2-F 4-CH3 S 1.0(2.5) nd 33.9(86) nd
12a Phenyl 4-Cl 4-CH3 S >40 nd nd nd
13a Phenyl 3-CF3 4-CH3 S >20 nd nd nd
14a Phenyl 4-CH3 4-CH3 S 1.0(2.6) nd 47.5(122) nd
15a Phenyl 3-CH3 4-CH3 S 0.5(1.3) nd 10.7(27) nd
16a Phenyl 2-CH3 4-CH3 S 1.0(2.5) nd 63.7(163) nd
17a Phenyl 3,5-CH3 4-CH3 S >20 nd nd nd
18a Phenyl 2,4-CH3 4-CH3 S >20 nd nd nd
19a Phenyl 3-OEt 4-CH3 S >20 nd nd nd
20a Phenyl 4-OH 4-CH3 S 0.5(1.3) 1(2.6) 79.1(202) nd
21a Phenyl 3-OH 4-CH3 S 0.5(1.3) nd 48.7(124) nd
22a Phenyl 2-OH 4-CH3 S 0.5(1.3) nd 53.1(135) nd
23a 4-Pyridine H 4-CH3 S 1.0(2.6) nd 29.9(79) nd
24a 3-Pyridine H 4-CH3 S 10(26) nd nd nd
25a 2-Pyridine 3-CH3 4-CH3 S >20 nd nd nd
26a 2-Pyridine 6-CH3 4-CH3 S 0.5(1.3) 1.0(2.6) 66.8(171) nd
27a 2-Pyridine 4-CH3 4-CH3 S 1.0(2.6) nd 86.3(221) nd
28a Phenyl 2-Cl, 4-CH3 4-CH3 S >20 nd nd nd
29a 4-Pyridazine H 4-CH3 S >20 nd nd nd
30a 2-Thiazole H 4-CH3 S >40 nd nd nd
31a 2-Thiazole 5-CH3 4-CH3 S >20 nd nd nd
32a 3-Thiophene H 4-CH3 S 1.0(2.6) 1.0(2.6) >100 nd
33a (Thiophen-2-yl)methyl H 4-CH3 S >20 nd nd nd
35b f Phenyl H 3,5-Cl S >20 nd nd nd
36b f 2-Pyridine H 3,5-Cl S >20 nd nd nd
35c Phenyl H 3,5-F S >20 nd nd nd
36c 2-Pyridine H 3,5-F S >20 nd nd nd
35d Phenyl H 3,5-CH3 S 1.0(2.5) nd 70.9(175) nd
36d 2-Pyridine H 3,5-CH3 S >20 nd nd nd
20e Phenyl 4-OH 3-OH,4-CH3 S 5.0(12.2) nd nd t1/2 = 19 ± 1
42e Phenyl H 3-OH,4-CH3 S 2.5(6.3) nd >100 nd
43e 2-Pyridine H 3-OH,4-CH3 S 5(12.6) nd >100 nd
42f Phenyl H 2-OH,4-CH3 S nd nd nd nd
43f 2-Pyridine H 2-OH,4-CH3 S >20 nd nd nd
42g Phenyl H H S 1.25(3.4) nd 11.9(33) t1/2 = 43 ± 3
43g 2-Pyridine H H S >20 nd nd t1/2 = 66 ± 9
42h Phenyl H 4-CF3 S >20 nd nd 71 ± 7 %
43h 2-Pyridine H 4-CF3 S >20 nd nd 85 ± 6 %
42j Phenyl H 3,4,5-Cl S >20 nd nd 101 ± 1 %
43j 2-Pyridine H 3,4,5-Cl S >20 nd nd 102 ± 6 %
42l Phenyl H 4-Cl S 1.25(3.2) 2(6.0) >100 t1/2 = 59 ± 9
42m Phenyl H 3-OH S 5.0(13.2) nd nd t1/2 = 34 ± 1
42n Phenyl H 4-CH2OH S >20 nd nd nd
43n 2-Pyridine H 4-CH2OH S >20 nd nd nd
47 Phenyl H 4-CH3 O 1.0(2.8) nd >100 nd
48 g 2-Pyridine H 4-CH3 O 2.5(6.9) nd 70.9(197) nd
34a graphic file with name nihms-1937709-t0015.jpg >20 nd >100 nd
42i graphic file with name nihms-1937709-t0016.jpg >20 nd nd 97 ± 12 %
43i graphic file with name nihms-1937709-t0017.jpg >20 nd nd 96 ± 14 %
53 graphic file with name nihms-1937709-t0018.jpg 1.25(3.8) nd >100 nd
SM h 0.25 nd nd nd
INH i 0.025 nd nd nd
a

Minimum Inhibitory Concentration, determined by REMA method toward M. tuberculosis H37Rv;[69]

b

Minimum Inhibitory Concentration, determined toward M. marinum ATCC BAA-535;

c

MTT assay has been used to assess the cytotoxicity of synthetized compounds toward Human monocytes THP-I cells;

d

in vitro metabolic stability in HLM was alternatively reported as half-life (t1/2) in min or as residual fraction (%) at 60 min if % compound at t=60 min was > 50%. Reported are Means ± S.E.M. (n=3).

e

Not Determined;

f

Activity for these compounds has already been reported;32

g

Activity for this compound has already been reported;49

h

Streptomycin;

i

Isoniazide.