Comparative Anti–Alzheimer’s Potential Evaluation of Curcumin and Curcumin Analogues obtained from ZINC Database: An in-Silico Validation
Abstract:
Curcumin and its eleven analogues obtained from the ZINC database were screened
for its anti-Alzheimer’s potential validated through in silico approach. Curcumin,
eleven curcumin analogues from the ZINC database, and six standard anti-Alzheimer’s
drugs were obtained from SWISS ADME and Pub chem database. All obtained molecules
were subjected to drug-likeness, molecular docking, and ADMET analysis. Curcumin
and eleven curcumin analogues show no violations against five drug-likeness rules,
whereas 2 standard drugs (CID_11269353, CID_46883536) out of 5 screened standard drug molecules shows violations
in drug likeness property. Curcumin and curcumin analogues
possess docking scores in the range of -7.5 to 9.9 Kcal/mol, whereas reference standard
drugs docking score lies in the range of -6.4 to -11.0 Kcal/mol against all three
Alzheimer’s disease molecular targets. Finally, our present study has proven that
curcumin analogues possess some novel anti-Alzheimer’s
properties over curcumin and standard reference drug. It needs to be validated and
commercialized after in vivo preclinical trials.
References:
[1] Alzheimer’s Association, 2015, Alzheimer’s disease
facts and figures. Alzheimers Dement,
11(3):332-84.
[2] Waldemar, G., Dubois, B., Emre, M., Georges, J., McKeith,
I.G., Rossor, M., Scheltens, P., Tariska, P., Winblad, B., 2007, Recommendations
for the diagnosis and management of Alzheimer’s disease and other disorders associated
with dementia: EFNS guideline, Eur J Neurol,14(1):1-26.
[3] Kumar, S., Chowdhury, S., 2014, Kinetics of acetylcholinesterase
inhibition by an aqueous extract of Cuminum cyminum seeds, Int J Appl Sci Biotechnol.
2(1):64–8.
[4] Kumar, S., Chowdhury, S., 2015, Kinetics of inhibition
of butyrylcholinesterase by an aqueous extract of Cuminum cyminum, Pharm Biol Eval,
2(1):25–8.
[5] Ul-Haq Z., Khan W., Kalsoom S., Ansari FL., 2010,
In silico modeling of the specific inhibitory potential of thiophene-2, 3-dihydro-1,5-benzothiazepine
against BChE in the formation of β-amyloid plaques associated with Alzheimer’s disease,
Theor Biol Med Model, 7(1):22.
[6] Zhang YW., Thompson R., Zhang H., Xu H., 2011, APP
processing in Alzheimer’s disease. Mol Brain, 4:3.
[7] Guzman-Martinez L., Calfío C., Farias GA., Vilches
C., Prieto R., Maccioni RB., 2021, New Frontiers in the Prevention, Diagnosis, and
Treatment of Alzheimer’s Disease, J Alzheimers Dis, 82(s1): S51-S63.
[8] Lleó, A., Greenberg, S.M., Growdon, J.H., 2006, Current
pharmacotherapy for Alzheimer’s disease, Annu. Rev. Med, 57: 513-533.
[9] Pohanka, M., 2011, Cholinesterases a target of pharmacology
and toxicology, Biomed. Pap. Med. Fac. Univ. Palacky Olomouc CzechRepub, 155(3):
219-229.
[10] Dunn B., Stein P., Cavazzoni P., 2021, Approval of
Aducanumab for Alzheimer Disease—The FDA’s Perspective, JAMA Intern Med, 181(10):1276–1278.
[11] Lanctot, K.L., Herrmann, N., Yau, K.K., Khan, L.R.,
Liu, B.A., Loulou, M.M., Einarson, T.R., 2003, Efficacy and safety of cholinesterase
inhibitors in Alzheimer’s disease: A meta-analysis, Can. Med. Assoc. J. 169(6):557–564.
[12] Veerman, S.R.T., Schulte, P.F.J., Smith, J.D., Haan,
L.D., 2016, Memantine augmentation in Clozapine-Refractory Schizophrenia: A Randomized,
Double-Blind, Placebo-Con- trolled Crossover Study, Psychol. Med ,46(9):1909–1921.
[13] Lieberman, AJ., Papadakis, K., Csernansky, J., Litman,
R., Volavka, J., Jia, XD., Gage, A., et al., v 2009, A Randomized, Placebo-Controlled
Study of Memantine as Adjunctive Treatment in Patients with Schizophrenia, Neuropsychopharmacol,
34:1322–1329.
[14] Shrikant Mishra and Kalpana Palanivelu., 2008, The
effect of curcumin (turmeric) on Alzheimer's disease: An overview, Ann Indian Acad
Neurol,11(1): 13–19.
[15] Noor H., Ikram A., Rathinavel T., Kumarasamy S., Nasir
Iqbal M., Bashir Z., 2021, Immunomodulatory and anti-cytokine therapeutic potential
of curcumin and its derivatives for treating COVID-19–a computational modeling,
J. Biomol. Struct. Dyn, 1–16.
[16] Ege D., 2021, Action Mechanisms of Curcumin in Alzheimer’s
Disease and Its Brain Targeted Delivery. Materials, 14: 3332.
[17] Berry A., Collacchi B., Masella R., Varì R., Cirulli
F., 2021, Curcuma Longa, the “Golden Spice” to Counteract Neuroinflammaging and
Cognitive Decline—What Have We Learned and What Needs to Be Done, Nutrients, 13:1519.
[18] Weininger D., 1988, SMILES, a chemical language and
information system Introduction to methodology and encoding rules, J. Chem. Inf.
Comput. Sci, 28(1):31–36.
[19] Berman HM., Westbrook J., Feng Z., Gilliland G., Bhat
T.N., Weissig H., Shindyalov IN., Bourne PE., 2000, The protein data bank, Nucleic
Acids Res, 28:235–242.
[20] Trott O., Olson AJ., 2010, AutoDock Vina: improving
the speed and accuracy of docking with a new scoring function, efficient optimization
and multithreading, J Comput Chem, 31:455–461.
[21] Daina A., Michielin O., Zoete V., 2017, SwissADME:
a free web tool to evaluate pharmaco kinetics, drug-likeness and medicinal chemistry
friendliness of small molecules, Sci. Rep, 7:42717.
[22] Chandrasekaran B., Abed SN., Al-Attraqchi O., Kuche
K., Tekade RK., 2018, Computer-aided prediction of pharmacokinetic (ADMET) properties.
In: Dosage form design parameters, Academic Press, 731–755.
[23] Wang Z., Yang H., Wu Z., Wang T., Li W., Tang Y.,
Liu G., 2018, In silico prediction of blood-brain barrier permeability of compounds
by machine learning and resampling methods, Chem. Med. Chem, 13:2189−2201.
[24] Tran, TS., Le, MT., Tran, TD., Tran, TH., Thai, KM, 2020, Design of Curcumin and Flavonoid Derivatives with Acetylcholinesterase and Beta-Secretase Inhibitory Activities Using in Silico Approaches, Molecules, 25(16):3644.
[25] Srinivasa Rao Kareti., Subash, P., 2020, In Silico
Molecular Docking Analysis of Potential Anti-Alzheimer's Compounds Present in Chloroform
Extract of Carissa carandas Leaf Using Gas Chromatography MS/MS, Curr Ther Res,
93: 100615.
[26] Kandagalla S., Sharath BS., Bharath BR., Hani U.,
Manjunatha H, 2017, Molecular docking analysis of curcumin analogues against kinase
domain of ALK5, In Silico Pharmacol, 5 (15):1–9.
[27] Lagorce, D., Douguet, D., Miteva, MA., Villoutreix,
BO., 2017, Computational analysis of calculated physicochemical and ADMET properties
of protein-protein interaction inhibitors, Sci. Rep 7:46277.