Molecular Docking and Pharmacophore Filtering in the Discovery of Dual-Inhibitors for Human Leukotriene A4 Hydrolase and Leukotriene C4 Synthase

2010 ◽  
Vol 51 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Sundarapandian Thangapandian ◽  
Shalini John ◽  
Sugunadevi Sakkiah ◽  
Keun Woo Lee
Keyword(s):  
Molecular Docking ◽  
Leukotriene C4 ◽  
Leukotriene A4 Hydrolase ◽  
Dual Inhibitors ◽  
Leukotriene A4 ◽  
Leukotriene C4 Synthase

scholarly journals 14,15-Dehydroleukotriene A4: a specific substrate for leukotriene C4 synthase

1997 ◽  
Vol 328 (1) ◽  
pp. 225-229 ◽  
Author(s):  
Angelo SALA ◽  
Mylene GARCIA ◽  
Simona ZARINI ◽  
Jean Claude ROSSI ◽  
Giancarlo FOLCO ◽  
...  
Keyword(s):  
Human Platelet ◽  
Leukotriene B4 ◽  
Reversed Phase ◽  
Human Platelets ◽  
Polymorphonuclear Leucocyte ◽  
Specific Substrate ◽  
Leukotriene C4 ◽  
Synthase Inhibitor ◽  
Leukotriene A4 ◽  
Leukotriene C4 Synthase

We studied the metabolism of 14,15-dehydro-leukotriene A4 (14,15-dehydro-LTA4) by human platelet leukotriene C4 (LTC4) synthase and polymorphonuclear leucocyte (PMNL) leukotriene A4 (LTA4) hydrolase. Metabolites were separated and identified using reversed-phase HPLC coupled to diode-array UV detection. Human platelets metabolize 14,15-dehydro-LTA4 to 14,15-dehydro-LTC4 with apparent kinetics identical with authentic LTA4. Metabolism to 14,15-dehydro-LTC4 is inhibited by MK-886, a reported LTC4 synthase inhibitor in human platelets, with a potency comparable with that shown by LTA4. In contrast, neither human red-blood-cell lysates nor human PMNL enzymically convert 14,15-dehydro-LTA4 into 14,15-dehydro-leukotriene B4. Minor amounts of 14,15-dehydro-LTC4, observed in some PMNL preparations, result from variable eosinophil contamination, as confirmed using highly purified neutrophil and eosinophil-enriched preparations. In addition, 14,15-dehydro-LTA4 irreversibly inhibits PMNL LTA4 hydrolase with an IC50 of 0.73 μM. The geometry of the methyl terminus of LTA4 does not influence the metabolism by human platelet LTC4 synthase. The double bond at C-14,15 is essential for the catalytic activity of LTA4 hydrolase but not for binding to this enzyme.

scholarly journals In silico molecular docking of quercetin as anti-colorectal cancer agents by inhibiting LT4AH

2021 ◽  
Vol 1 (2) ◽  
pp. 16
Author(s):  
Made Agus Widiana Saputra ◽  
Anak Agung Istri Rani Mahaswari ◽  
Ni Ketut Sri Anggreni ◽  
Wahyu Nadi Eka Putri ◽  
Ni Putu Linda Laksmiani
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Malignant Neoplasm ◽  
Docking Method ◽  
Leukotriene A4 Hydrolase ◽  
Leukotriene A4 ◽  
In Silico Molecular Docking ◽  
Native Ligand

Colorectal cancer is a malignant neoplasm originating from the colon or rectum. Overexpression of leukotriene A4 hydrolase (LTA4H) increases the growth of HCT116 colon cancer cells, therefore, this enzyme becomes an attractive target for commercial drug bestatin. Meanwhile, quercetin is a member of flavonoids possessing a wide variety of anticancer. This study aimed to determine the potential of quercetin as anti-colorectal cancer by inhibiting LTA4H through in silico molecular docking. The docking process involved optimizing quercetin structure, preparing LTA4H protein (PDB ID: 3U9W), validating the molecular docking method, and docking quercetin and bestatin on LTA4H. The binding energy of quercetin to LTA4H was -9.57 kcal/mol, while 28P native ligand and bestatin yielded -10.22 kcal/mol and -9.10 kcal/mol, respectively. Based on the binding energy value, quercetin has a potential inhibitory against the LTA4H.

Leukotriene C4 Synthase: Upcoming Drug Target For Inflammation

2012 ◽  
Vol 13 (8) ◽  
pp. 1114-1125 ◽  
Author(s):  
Nisha S. Devi ◽  
Mukesh Doble
Keyword(s):  
Drug Target ◽  
Leukotriene C4 ◽  
Leukotriene C4 Synthase
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