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. 2024 Feb 8;25(4):2092. doi: 10.3390/ijms25042092

Table 4.

Summary of selected bacterial nicotinate mononucleotide adenylyltransferase (NadD) and NAD+ synthetase (NadE) inhibitors and their reported activities.

Name and Structure Enzyme Inhibition (IC50/Ki) Antibacterial/Antiparasitic Activity (MIC) Antitumor Activity
Compound 3_02
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Inhibits nicotinate mononucleotide adenylyltransferases of E. coli (IC50 = 65 µM, Ki = 25 ± 9 µM toward NAMN and 21 ± 9 µM toward ATP) and B. anthracis (IC50 = 36 µM, Ki = 18 ± 4 µM toward NAMN and 32 ± 5 µM toward ATP) but not human NMNAT1-3 [142] Reduces the growth of E. coli (MIC50 = 160 µM), B. anthracis and B. subtilis (MIC50 = 80 µM) [142] N/A
Compound 1_02
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Inhibits nicotinate mononucleotide adenylyltransferases of E. coli (IC50 = 15 µM, Ki = 8 ± 3 µM toward NAMN and 5 ± 1 µM toward ATP) and B. anthracis (IC50 = 25 µM, Ki = 9 ± 3 µM toward NAMN and 10 ± 2 µM toward ATP) but not human NMNAT1-3 [142] Reduces the growth of E. coli (MIC50> 80 µM) [142] N/A
Compound 1_03
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Inhibits nicotinate mononucleotide adenylyltransferases of E. coli (IC50 = 18 µM), B. anthracis (IC50 = 33 µM) [142], and P. falciparum [162], but not human NMNAT1-3 [142] Reduces the growth of E. coli (MIC50> 80 µM), B. anthracis (MIC50 = 15 µM) and B. subtilis (MIC50 = 10 µM) [142]
Suppresses the growth of the P. falciparum parasite (MIC50 = 50 µM [163] and 8.09 ± 5.11 µM [162]) and arrests its growth inside the erythrocytes at the trophozoite stage (at 100 µM) [163]
N/A
Compound N2-11
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Inhibits nicotinate mononucleotide adenylyltransferases of M. tuberculosis (IC50 = 6 ± 1 µM) [164] Reduces the growth of M. smegmatis (MIC = 5 µM), and M. tuberculosis (MIC = 28.2 µM) [164] N/A
Compound 5824
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Inhibits NAD+ synthetase of B. anthracis (IC50 = 6.4 µM and 10 µM) [161,165]
Inhibits nicotinate mononucleotide adenylyltransferases of B. anthracis (IC50 = 2 µM) [165]
Inhibits the activity of human NAD+ synthetase enzyme (NADSYN1) in a dose-dependent manner (i.e., at 1, 2, and 3 µM) [69]
Reduces the growth of B. anthracis (MIC = 1.9 µM in LB media and 2.8 µM in MH media) [165]
Reduces the viability of L. donovani promastigotes at micromolar concentrations [166]
Reduces NAD+ levels and the viability of several PH-amplified cancer cell lines but not normal cells [69]
Represses the growth of PH-amplified OV4 ovarian cancer tumors in vivo [69]
Compound 5{1}
Inline graphic
Inhibits NAD+ synthetase of B. anthracis (IC50 = 32.7 µM) [161]
Inhibits nicotinate mononucleotide adenylyltransferase of B. anthracis (IC50 = 7.3 µM) [161]
Reduces the growth of B. anthracis (MIC = 2.8 µM in LB media and 3.8 µM in MH media) [161] N/A
Compound VIB8E
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Inhibits NAD+ synthetase of B. subtilis (IC50 = 20 µM) [167] Reduces the growth of gram-positive bacteria such as B. subtilis (MIC = 6.2 µM), S. aureus (MIC = 1.5 µM), and methicillin-resistant S. aureus (MIC is between 3.1 and 12.5 µM), but not gram-negative bacteria such as S. enteritidis and P. aeruginosa [167] N/A
Compound VD1
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Inhibits NAD+ synthetase of B. subtilis (IC50 = 20 µM) [168] Reduces the growth of gram-positive bacteria such as B. subtilis (MIC = 2 µg/mL), S. aureus (MIC = 9.4 µg/mL), and methicillin-resistant S. aureus (MIC = 3.1 and 6.2 µg/mL), but not gram-negative bacteria such as S. enteritidis and P. aeruginosa [168] N/A
Compound 2A
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Inhibits NAD+ synthetase of B. subtilis (IC50 = 22 ± 2.4 µM) [169] Reduces the growth of gram-positive bacteria such as B. subtilis, S. aureus, and methicillin-resistant S. aureus (MIC = 0.78 µM for all), but not P. aeruginosa [169] N/A
Compound 4f
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Inhibits NAD+ synthetase of M. tuberculosis (IC50 = 90 ± 5 µM) [170] Reduces the growth of M. tuberculosis (MIC = 37 µg/mL in rich media and 25 µg/mL in minimal media) [170] N/A

N/A; Not available.