Sclerotiorin inhibits protein kinase G from Mycobacterium tuberculosis and impairs mycobacterial growth in macrophages

Targeting the messengers: Serine/threonine protein kinases as potential targets for antimycobacterial drug development

“…Additionally, a nitro‐fatty acid was tested to be a potent inhibitor of PknG , wherein the fatty acid nitroalkenes reacts with crucial cysteine residues of thioredoxin domain, impairing the PknG activity . Sclerotiorin, derived from marine fungi, has also been reported to be a non‐competitive inhibitor of PknG . Consistent with the role of PknG, this inhibitor has no bactericidal effects in vitro , but led to substantial reduction in the bacterial survival in infected macrophages.…”

“…Consistent with the role of PknG, this inhibitor has no bactericidal effects in vitro , but led to substantial reduction in the bacterial survival in infected macrophages. Docking studies suggested sclerotiorin interacts with the P‐loop and the catalytic loop of PknG . Another molecular docking studies with 40 withanolide derivates, an ayurvedic herb, suggested four compounds withanolide E, D, F and withaferin inhibited PknG.…”

Recent advances for identification of new scaffolds and drug targets for Mycobacterium tuberculosis

“…PknG inhibits phagosome‐lysosome fusion and its deletion enhances susceptibility of M. tuberculosis to drugs, impairs growth in stationary phase, biofilms, and guinea pigs . PknG has been identified as a target for novel antimicrobial compounds such as sclerotiorin, aminopyrimidine derivative, and azaphilone derivatives . In addition to STPKs, two component systems are also essential for M. tuberculosis virulence and adaptation to different stress conditions.…”

Recent advances in the chemistry and biology of azaphilones

“…19 Cytotoxic (L5178Y: 26.20% at 10 mg mL À1 ) (3S)-6-Hydroxy-8-methoxy-3-methylisochroman (9) Penicillium sp. 19 Cytotoxic (L5178Y: 16.10% at 10 mg mL À1 ) (S)-3,6-Dihydroxy-8-methoxy-3methylisochroman-4-one (10) Aspergillus fumigatus 20 Cytotoxic (MV4-11: 38.39 mM) (R)-3,6-Dihydroxy-8-methox-3methylisochroman-4-one (11) Aspergillus fumigatus 20 8-Methoxy-3-methylisochromane-3,6-diol (12) Aspergillus fumigatus 20 Cytotoxic (MV4-11: 30.00 mM) 3,8-Dimethoxy-3-methylisochroman-6-ol (13) Aspergillus fumigatus 20 3,6,7,8-Tetramethoxy-3-methylisochromane (14) Aspergillus fumigatus 20 Colletobredin A (15) Colletotrichum aotearoa BCRC 09F0161 21 Anti-inammatory (inhibit NO production: 182.2 mM) Colletobredins B-D (16)(17)(18) Colletotrichum aotearoa BCRC 09F0161 21 Monascuspilorin (19) Monascus pilosus BCRC 38072 22 Monascupurpurin (20) Monascus purpureus BCRC 31499 23 Peyronellone A (21) Peyronellaea glomerate 6 Antioxidant (ABTS: 88.8 mM, DPPH: 126.3 mM) Peyronellone B (22) Peyronellaea glomerate 6 Antioxidant (ABTS: 95.2 mM, DPPH: 83.5 mM); hypoxia-protective activity (improved the survival rate of H/R-treated human umbilical vein endothelial cells from 35% to 70% at 5 mM) Penicitol A (23) Penicillium chrysogenum HND11-24 24 Cytotoxic (HeLa: 4.6 mM, BEL-7402: 10.5 mM, HEK-293: 6.7 mM, HCT-116: 5.6 mM, A549: 7.6 mM) Citrifuran A (24) Aspergillus sp. 7 Anti-inammatory (inhibit NO production: 18.3 mM) Citrifuran B (25) Aspergillus sp.…”

“…18 The fungus Penicillium sp., collected in the sediment of the hyper saline lake Wadi El-Natrun in Egypt, produced two novel cytotoxic citrinin analogues, (3S,4R)-6-hydroxy-8-methoxy-3,5dimethyl isochromanol (8) and (3S)-6-hydroxy-8-methoxy-3methylisochroman (9). 19 An endophytic fungus from Cordyceps sinensis, Aspergillus fumigatus, gave ve new isochromanes (10)(11)(12)(13)(14), among which 10 and 11 were determined as a pair of enantiomers puried by chiral HPLC methods. 20 Meanwhile, 10 and 12 exhibited moderate activities against MV4-11 cell line with IC 50 values of 38.4 and 30.0 mM, respectively.…”