Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors as anti-Alzheimer’s agents through pharmacophore-based virtual screening, molecular docking and experimental validation

Zhang XX, Tian Y, Wang ZT, Ma YH, Tan L, Yu JT. The epidemiology of Alzheimer’s disease modifiable risk factors and prevention. J Prev Alzheimers Dis. 2021;8:313–21. https://doi.org/10.14283/jpad.2021.15

Article  PubMed  Google Scholar 

Alzheimer’s Association. 2022 Alzheimer’s disease facts and figures. 2022

Jain S, Bisht A, Verma K, Negi S, Paliwal S, Sharma S. The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer’s disease. Cell Biochem Funct. 2021. https://doi.org/10.1002/CBF.3680

D’Addario C, Di Francesco A, Arosio B, Gussago C, Dell’Osso B, Bari M, et al. Epigenetic regulation of fatty acid amide hydrolase in Alzheimer disease. PLoS ONE. 2012;7:1–7. https://doi.org/10.1371/journal.pone.0039186

Article  CAS  Google Scholar 

Tanaka M, Yagyu K, Sackett S, Zhang Y. Anti-inflammatory effects by pharmacological inhibition or knockdown of fatty acid amide hydrolase in BV2 microglial cells. Cells. 2019;8:491. https://doi.org/10.3390/cells8050491

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kumbhar N, Nimal S, Barale S, Kamble S, Bavi R, Sonawane K, et al. Identification of novel leads as potent inhibitors of HDAC3 using ligand-based pharmacophore modeling and MD simulation. Sci Rep. 2022;12:1–21. https://doi.org/10.1038/s41598-022-05698-7

Article  CAS  Google Scholar 

Kesar S, Paliwal S, Mishra P, Madan K, Chauhan M, Chauhan N, et al. Identification of novel Rho-Kinase-II inhibitors with vasodilatory activity. ACS Med Chem Lett. 2020;11:1694–703. https://doi.org/10.1021/acsmedchemlett.0c00126

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sharma M, Mittal A, Singh A, Jainarayanan AK, Sharma S, Paliwal S. Pharmacophore-driven identification of N-methyl-D-receptor antagonists as potent neuroprotective agents validated using in vivo studies. Biol Methods Protoc. 2021;5:1–12. https://doi.org/10.1093/biomethods/bpaa013

Article  CAS  Google Scholar 

Wu J, Zhang P, Zhang L, Meng W, Li J, Tong C, et al. Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results. MedRxiv. 2020. https://doi.org/10.1101/2020.04.02.20051136

Chaudhari P, Bari S. In silico exploration of c-KIT inhibitors by pharmaco-informatics methodology: pharmacophore modeling, 3D QSAR, docking studies, and virtual screening. Mol Divers. 2016;20:41–53. https://doi.org/10.1007/S11030-015-9635-X/FIGURES/7

Article  CAS  PubMed  Google Scholar 

Tripathi N, Paliwal S, Sharma S, Verma K, Gururani R, Tiwari A, et al. Discovery of novel soluble epoxide hydrolase inhibitors as potent vasodilators. Sci Rep. 2018;8:1–11. https://doi.org/10.1038/s41598-018-32449-4

Article  CAS  Google Scholar 

Palermo G, Favia AD, Convertino M, De Vivo M. The molecular basis for dual fatty acid amide hydrolase (FAAH)/cyclooxygenase (COX) inhibition. ChemMedChem. 2016:1252–8. https://doi.org/10.1002/cmdc.201500507

Ahn K, Johnson DS, Fitzgerald LR, Liimatta M, Arendse A, Stevenson T, et al. Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity. Biochemistry. 2007;46:13019–30. https://doi.org/10.1021/bi701378g

Article  CAS  PubMed  Google Scholar 

Criscuolo E, De Sciscio ML, Fezza F, Maccarrone M. In silico and in vitro analysis of major cannabis-derived compounds as fatty acid amide hydrolase inhibitors. Molecules. 2021;26:48. https://doi.org/10.3390/MOLECULES26010048

Article  CAS  Google Scholar 

Jaiswal S, Tripathi RKP, Ayyannan SR. Scaffold hopping-guided design of some isatin based rigid analogs as fatty acid amide hydrolase inhibitors: synthesis and evaluation. Biomed Pharmacother. 2018;107:1611–23. https://doi.org/10.1016/J.BIOPHA.2018.08.125

Article  CAS  PubMed  Google Scholar 

Moreira-Silva D, Carrettiero DC, Oliveira ASA, Rodrigues S, Dos Santos-Lopes J, Canas PM, et al. Anandamide effects in a streptozotocin-induced Alzheimer’s disease-like sporadic dementia in rats. Front Neurosci. 2018;12:1–14. https://doi.org/10.3389/fnins.2018.00653

Article  Google Scholar 

Hasegawa Y, Inoue T, Kawaminami S, Fujita M. Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity. Asian Pac J Trop Med. 2016;9:662–7. https://doi.org/10.1016/j.apjtm.2016.05.019

Article  CAS  PubMed  Google Scholar 

Foyet HS, Keugong Wado E, Ngatanko Abaissou HH, Assongalem EA, Eyong OK. Anticholinesterase and antioxidant potential of hydromethanolic extract of Ziziphus mucronata (Rhamnaceae) leaves on scopolamine-induced memory and cognitive dysfunctions in mice. Evid Based Complement Alternat Med. 2019;2019. https://doi.org/10.1155/2019/4568401

Li C, Shi J, Wang B, Li J, Jia H. CB2 cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice. Neurosci Lett. 2019;707:134286. https://doi.org/10.1016/j.neulet.2019.134286

Article  CAS  PubMed  Google Scholar 

Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med. 2008;14:949–53. https://doi.org/10.1038/nm.1855

Article  CAS  PubMed  Google Scholar 

Gao Y, Xu Y, Yin J. Selenomethionine ameliorates cognitive impairment, decreases hippocampal oxidative stress and attenuates dysbiosis in d-galactose-treated mice. Antioxidants. 2022;11. https://doi.org/10.3390/antiox11010111

Patel S, Gururani R, Jain S, Tripathi N, Paliwal S, Paliwal S, et al. Repurposing of digoxin in pain and inflammation: an evidence-based study. Drug Dev Res. 2022;83:1097–110. https://doi.org/10.1002/ddr.21935

Article  CAS  PubMed  Google Scholar 

Patel S, Shukla J, Jain S, Paliwal V, Tripathi N, Paliwal S, et al. Repositioning of tubocurarine as analgesic and anti-inflammatory agent: exploring beyond myorelaxant activity. Biochem Pharm. 2022;205:115248. https://doi.org/10.1016/j.bcp.2022.115248

Article  CAS  PubMed  Google Scholar 

Nazir N, Zahoor M, Nisar M, Karim N, Latif A, Ahmad S, et al. Evaluation of neuroprotective and antiamnesic effects of Elaeagnus umbellate thunb. On scopolamine-induced memory impairment in mice. BMC Complement Med Ther. 2020;20:1–17. https://doi.org/10.1186/s12906-020-02942-3

Article  CAS  Google Scholar 

Sun XY, Li LJ, Dong QX, Zhu J, Huang YR, Hou SJ, et al. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2021;18:1–14. https://doi.org/10.1186/s12974-021-02182-3

Article  CAS  Google Scholar 

El Sayed NS, Ghoneum MH. Antia, a natural antioxidant product, attenuates cognitive dysfunction in streptozotocin-induced mouse model of sporadic Alzheimer’s disease by targeting the amyloidogenic, inflammatory, autophagy, and oxidative stress pathways. Oxid Med Cell Longev. 2020;2020. https://doi.org/10.1155/2020/4386562

Sirwi A, Sayed NSE, Abdallah HM, Ibrahim SRM, Mohamed GA, El-Halawany AM, et al. Umuhengerin neuroprotective effects in streptozotocin-induced Alzheimer’s disease mouse model via targeting nrf2 and nf-kβ signaling cascades. Antioxidants. 2021;10. https://doi.org/10.3390/antiox10122011

Tak K, Sharma P, Sharma R, Dave V, Jain S, Sharma S. One-pot hydrothermal green synthesis of Polygala tenuifolia mediated graphene quantum dots for acetylcholine esterase inhibitory activity. J Drug Deliv Sci Technol. 2022;73:103486. https://doi.org/10.1016/j.jddst.2022.103486

Article  CAS  Google Scholar 

Fan F, Warshaviak DT, Hamadeh HK, Dunn RT. The integration of pharmacophore-based 3D QSAR modeling and virtual screening in safety profiling: A case study to identify antagonistic activities against adenosine receptor, A2A, using 1,897 known drugs. PLoS ONE. 2019;14:1–23. https://doi.org/10.1371/journal.pone.0204378

Article  CAS  Google Scholar 

Holtfrerich A, Hanekamp W, Lehr M. (4-Phenoxyphenyl) tetrazolecarboxamides and related compounds as dual inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Eur J Med Chem. 2013;63:64–75. https://doi.org/10.1016/j.ejmech.2013.01.050

Article  CAS  PubMed  Google Scholar 

Agarwal A, Paliwal S, Mishra R, Sharma S, Kumar Dwivedi A, Tripathi R, et al. Discovery of a selective, safe and novel anti-malarial compound with activity against chloroquine resistant strain of Plasmodium falciparum. Sci Rep. 2015;5:1–8. https://doi.org/10.1038/srep13838

Article  CAS  Google Scholar 

Opo FADM, Rahman MM, Ahammad F, Ahmed I, Bhuiyan MA, Asiri AM. Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein. Sci Rep. 2021;11:1–18. https://doi.org/10.1038/s41598-021-83626-x

Article  CAS  Google Scholar 

Ferraz WR, Gomes RA, Novaes ALS, Goulart Trossini GH. Ligand and structure-based virtual screening applied to the SARS-CoV-2 main protease: an in silico repurposing study. Future Med Chem. 2020;12:1815–28. https://doi.org/10.4155/fmc-2020-0165

Article  CAS  PubMed  Google Scholar 

Zhao D, Wang H, Lian Z, Han D, Jin X. Pharmacophore modeling and virtual screening for the discovery of new fatty acid amide hydrolase inhibitors. Acta Pharm Sin B. 2011;1:27–35. https://doi.org/10.1016/j.apsb.2011.04.003

Article  CAS  Google Scholar 

Ng’uni T, Klaasen JA, Fielding BC. Acute toxicity studies of the South African medicinal plant Galenia africana. Toxicol Rep. 2018;5:813–8. https://doi.org/10.1016/j.toxrep.2018.08.008

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moreira S, Jansen A, Silva F. Dietary interventions and cognition daily functioning and dementia of Alzheimer’s disease patients. Dement Neuropsychol. 2020;14:258–82

Article  PubMed  PubMed Central  Google Scholar 

Moon M, Jung ES, Jeon SG, Cha MY, Jang Y, Kim W, et al. Nurr1 (NR4A2) regulates Alzheimer’s disease-related pathogenesis and cognitive function in the 5XFAD mouse model. Aging Cell. 2019;18:1–11. https://doi.org/10.1111/acel.12866

Article  CAS  Google Scholar 

Fan M, Liu S, Sun HM, Ma MD, Gao YJ, Qi CC, et al. Bilateral intracerebroventricular injection of streptozotocin induces AD-like behavioral impairments and neuropathological features in mice: involved with the fundamental role of neuroinflammation. Biomed Pharmacother. 2022;153:113375. https://doi.org/10.1016/J.BIOPHA.2022.113375

Article  CAS  PubMed  Google Scholar 

Foyet HS, Ngatanko Abaïssou HH, Wado E, Asongalem Acha E, Alin C. Emilia coccinae (SIMS) G extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in scopolamine-treated rats. BMC Complement Alter Med. 2015;15:1–12. https://doi.org/10.1186/s12906-015-0864-4

Article  CAS  Google Scholar 

Barai P, Raval N, Acharya S, Acharya N. Bergenia ciliata ameliorates streptozotocin-induced spatial memory deficits through dual cholinesterase inhibition and attenuation of oxidative stress in rats. Biomed Pharmacother. 2018;102:966–80.

Comments (0)

No login
gif