BioMed Research International

Review Article

Potential Inhibitors for Isocitrate Lyase of Mycobacterium tuberculosis and Non-M. tuberculosis: A Summary

Table 1

Summary of potential inhibitors for MTB and non-MTB isocitrate lyase (ICL).


Number	Published year	Inhibitor	Source	Description	Target ICL	Inhibitio (IC₅₀)	Remarks

1	1977	Itaconate [11, 14]	Synthetic	Succinate analog	Pseudomonas indigofera	= 120	Established inhibitor

2	1982	3-Nitropropionate [11, 15]	Synthetic	Succinate analog	Pseudomonas indigofera	= 120	Established inhibitor

3	1990	Mycenon [60]	Mycena sp.	Fungi	Acinetobacter calcoaceticus Neurospora crassa Ricinus communis	5.2 M 7.4 M	No information on positive control

4	1990	3-Bromopyruvate [11, 16]	Synthetic	Glyoxylate analog	Escherichia coli	3 M	Established inhibitor

5	2005	DNAzyme [41]	Synthetic	—	Mycobacterium tuberculosis	—

6	2006	Extract of traditional Chinese medicine [30]	Zingiber officinale, Illicium verum	Plant	Mycobacterium tuberculosis	47.7 μg/mL 18.2 μg/mL	Positive control IC₅₀ of itaconate = 90 g/mL (good inhibitory)

7	2007	Hydroquinone derivatives [62]	Synthetic	—	Candida albicans	0.28–1.02 mM	Positive control IC₅₀ of itaconate = 0.06 mM (weak inhibitory)

8	2007	Halisulfate 1 [46, 47]	Hippospongia sp.	Marine sponge	Magnaporthe grisea	12.6 M	No information on positive control (high inhibitory)

9	2007	Bromophenols [27]	Odonthalia corymbifera	Red algae	Magnaporthe grisea	2.0–2.8 M	Positive control IC₅₀ of 3-nitropropionate = 94.2 M (high inhibitory)

10	2008	Polyoxygenated diterpenes [61]	Phorbas sp.	Marine sponge	—	LC₅₀ of 55–140 g/mL	No information on positive control (weak inhibitory)

11	2008	Meroditerpenoids [48]	Sargassum siliquastrum	Brown algae	Candida albicans	50–95 g/mL	No information on positive control (weak inhibitory)

12	2008	Dihydroxystyrene metabolites [49]	Association of Poecillastra wondoensis and Jaspis sp.	Marine sponge	Candida albicans	28.7 to >200 μg/mL	Positive control IC₅₀ of itaconate = 5.8 g/mL (weak to moderate inhibitory)

13	2008	Sesterterpenoids [50]	Sarcotragus sp.	Marine sponge	Candida albicans	12.5–19.9 g/mL	Positive control IC₅₀ of Itaconate = 4.9 g/mL (moderate to high inhibitory)

14	2008	Sesterterpene sulfates [51]	Dysidea sp.	Marine sponge	Candida albicans	31.3–33.8 M	Positive control IC₅₀ of 3-nitropropionate = 50.7 M (high inhibitory)

15	2009	Pthalazinyl derivatives [35]	Synthetic	—	Mycobacterium tuberculosis	45–61% inhibition at 10 M	Positive control 3-nitropropionate has 63.2% inhibition at 100 M

16	2009	Hyrtiosin B [52]	Hyrtios sp.	Marine sponge	Candida albicans	89 M	Positive control IC₅₀ of 3-nitropropionate = 50.7 M (high inhibitory)

17	2010	Phthalazin-4-ylacetamides [36]	Synthetic	—	Mycobacterium tuberculosis	40.62–66% inhibition at 10 M	Positive control 3-nitropropionate has 68.2% inhibition at 100 M

18	2010	Extract of traditional Chinese medicine (I2906) [31]	—	Plant	Mycobacterium tuberculosis	134 g/mL	Control samples were untreated samples

19	2010	5-Nitro-2-furoic acid hydrazones with furan-2-carbaldehyde [37]	Synthetic	—	Mycobacterium tuberculosis	86.8% inhibition at 10 mM	Positive control 3-nitropropionate has 63.2% inhibition at 100 M (good inhibitory)

20	2010	Bromophenols [63]	Synthetic	—	Candida albicans	2.65 M	Positive control IC₅₀ of 3-nitropropionate = 50.7 μM (high inhibitory)

21	2010	5-Nitro-2,6-dioxohexahydro-4-pyrimidinecarboxamides [38]	Synthetic	—	Mycobacterium tuberculosis	45.7% inhibition at 10 mM	Positive control 3-nitropropionate has 68.2% inhibition at 100 M (good inhibitory)

22	2010	Indole-containing natural compound (analog) [64]	Synthetic	—	Candida albicans	75 M	Positive control IC₅₀ of 3-nitropropionate = 50 M (high inhibitory)

23	2010	Isatinyl thiosemicarbazones derivatives [39]	Synthetic	—	Mycobacterium tuberculosis	63.44% inhibition at 10 mM	Positive control 3-nitropropionate has 65.9% inhibition at 100 mM (good inhibitory)

24	2011	Brominated resorcinol dimer [65]	Synthetic	—	Candida albicans	28 M	Positive control IC₅₀ of 3-nitropropionate = 6.0 M (good inhibitory)

25	2011	Sargachromanols [53]	Sargassum siliquastrum	Brown algae	Candida albicans	118.4–172.9 M	Positive control IC₅₀ of 3-nitropropionate = 34.8 M (moderate inhibitory)

26	2011	Scalarane sesterterpenes [54]	Hyatella sp.	Marine sponge	Candida albicans	40.8–55.3 M	Positive control IC₅₀ of 3-nitropropionate = 27.9 M (weak inhibitory)

27	2011	Suvanine salt [55]	Coscinoderma sp.	Marine sponge	Candida albicans	5–17 M	Positive control IC₅₀ of 3-nitropropionate = 27.9 M (moderate inhibitory)

28	2011	Chelerythrine extract [32]	Chelidonium majus	Plant	Mycobacterium tuberculosis	Expression level decreased 5 fold	—

29	2011	Mannich base, Ydcm67 [42]	Synthetic	—	Mycobacterium tuberculosis	57.4% inhibition at 0.05 mg/mL	Positive control oxalic acid has 95.55% inhibition at 0.05 M

30	2011	Peptide inhibitor [43]	Synthetic	—	Mycobacterium tuberculosis	Inhibition rate 38.2–47.92%	Samples contain no peptide inhibitor or ICL in reaction system as controls

31	2011	3-Nitropropionamides derivatives [40]	Synthetic	—	Mycobacterium tuberculosis	0.1 M	Positive control IC₅₀ of 3-nitropropionate = 116.0 M (good inhibitory)

32	2012	Pyruvate-isoniazid analog with their copper complex [45]	Synthetic	—	Mycobacterium tuberculosis	Inhibition rate 6–92%	Control docking using pyruvic acid

33	2012	Bahamaolides A (macrolide) [56]	Streptomyces sp.	Actinomycete (Actinobacteria)	Candida albicans	10.8 M	Positive control IC₅₀ of 3-nitropropionate = 20.1 M (high inhibitory)

34	2012	Beta-carboline alkaloid [57]	Synoicum sp.	Ascidian (sea squirt)	Candida albicans	48.2–68.9 M	Positive control IC₅₀ of 3-nitropropionate = 38.6 M (weak inhibitory)

35	2012	Sphingolipid [58]	Spirastrella abata	Marine sponge	Candida albicans	2–87 M	Positive control IC₅₀ of 3-nitropropionate = 1.0 M (weak to moderate inhibitory)

36	2012	Thio benzanilide [66]	Synthetic	—	Mycobacterium tuberculosis	21–23% inhibition at 10 mol/L	Positive control 3-nitropropionate has 25% inhibition at 10–100 mol/L

38	2012	Salicylanilide derivatives [67]	Synthetic	—	Mycobacterium tuberculosis	22–59% inhibition at 10–100 mol/L	Positive control 3-nitropropionate has 25–67% inhibition at 10–100 mol/L

39	2013	Tris-aromatic furanones [59]	Synoicum sp.	Ascidian (sea squirt)	Candida albicans	7.62–10.36 M	Positive control IC₅₀ of 3-nitropropionate = 13.91 M (Good inhibitory)

40	2013	Heptapeptide [44]	Synthetic	—	Mycobacterium tuberculosis	126 M	Positive control IC₅₀ of 3-nitropropionate = 50.7 M (good inhibitory)

Inhibition default unit is IC₅₀ unless other units are mentioned in the table.
Inhibitory potential of potential inhibitors was evaluated by the respective authors.