Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Perspective Article

Privileged Pharmacophore of FDA Approved Drugs in Combination with Chalcone Framework: A New Hope for Alzheimer’s Treatment

Author(s): Bijo Mathew*

Volume 23 , Issue 9 , 2020

Page: [842 - 846] Pages: 5

DOI: 10.2174/1386207323999200728122627

Price: $65

Abstract

Multi-functional design of ligands emerged as a new drug design paradigm of Alzheimer’s disease (AD). Given the complexity of AD, the molecules showing dual inhibition of monoamine oxidase (MAO) and acetylcholinesterase (AChE) with neuroprotective properties could prevent the progressive neural degeneration effectively. Numerous studies documented that chalcone is a privileged structural framework for the inhibition of both MAO and AChE. The recent studies suggested that the development of chalcone candidates endowed with pharmacophores of FDA approved drugs may become an active molecules in the field of current AD research. The current perspective described the recent updates of chalcone moiety linked with the pharmacophores of flurbiprofen and rivastigmine hybrids as selective ChE/MAO-B inhibitors for the prophylactic agents for AD.

Keywords: Chalcones, pharmacophore, monoamine oxidase, acetylcholinesterase, flurbiprofen, rivastigmine.

[1]
Kabir, M.T.; Uddin, M.S.; Begum, M.M.; Thangapandiyan, S.; Rahman, M.S.; Aleya, L.; Mathew, B.; Ahmed, M.; Barreto, G.E.; Ashraf, G.M. Cholinesterase inhibitors for Alzheimer’s disease: multitargeting strategy based on anti-Alzheimer’s drugs repositioning. Curr. Pharm. Des., 2019, 25(33), 3519-3535.
[http://dx.doi.org/10.2174/1381612825666191008103141] [PMID: 31593530]
[2]
Mamun, A.A.; Uddin, M.S.; Mathew, B.; Ashraf, G.M. Toxic tau: structural origins of tau aggregation in Alzheimer’s disease. Neural Regen. Res., 2020, 15(8), 1417-1420.
[http://dx.doi.org/10.4103/1673-5374.274329] [PMID: 31997800]
[3]
Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Mathew, G.E.; Uddin, M.S.; Kim, H.; Mathew, B. Advancements in nanotherapeutics for Alzheimer’s disease: current perspectives. J. Pharm. Pharmacol., 2019, 71(9), 1370-1383.
[http://dx.doi.org/10.1111/jphp.13132] [PMID: 31304982]
[4]
Kabir, M.T.; Uddin, M.S.; Mamun, A.A.; Jeandet, P.; Aleya, L.; Mansouri, R.A.; Ashraf, G.M.; Mathew, B.; Bin-Jumah, M.N.; Abdel-Daim, M.M. Combination drug therapy for the management of Alzheimer’s disease. Int. J. Mol. Sci., 2020, 21(9), 3272.
[http://dx.doi.org/10.3390/ijms21093272] [PMID: 32380758]
[5]
Mathew, B.; Baek, S.C.; Grace Thomas Parambi, D.; Pil Lee, J.; Joy, M.; Annie Rilda, P.R.; Randev, R.V.; Nithyamol, P.; Vijayan, V.; Inasu, S.T.; Mathew, G.E.; Lohidakshan, K.K.; Kumar Krishnan, G.; Kim, H. Selected aryl thiosemicarbazones as a new class of multi-targeted monoamine oxidase inhibitors. MedChemComm, 2018, 9(11), 1871-1881.
[http://dx.doi.org/10.1039/C8MD00399H] [PMID: 30568755]
[6]
Mathew, B.; Mathew, G.E.; Petzer, J.P.; Petzer, A. Structural exploration of synthetic chromones as selective MAO-B inhibitors. A mini review. Comb. Chem. High Throughput Screen., 2017, 20(6), 522-532.
[http://dx.doi.org/10.2174/1386207320666170227155517] [PMID: 28245770]
[7]
Kavully, F.S.; Oh, J.M.; Dev, S.; Kaipakasseri, S.; Palakkathondi, A.; Vengamthodi, A.; Abdul Azeez, R.F.; Tondo, A.R.; Nicolotti, O.; Kim, H.; Mathew, B. Design of enamides as new selective monoamine oxidase-B inhibitors. J. Pharm. Pharmacol., 2020, 72(7), 916-926.
[http://dx.doi.org/10.1111/jphp.13264] [PMID: 32246471]
[8]
Mathew, B.; Mathew, G.E.; Suresh, J.; Ucar, G.; Sasidharan, R.; Vilapurathu, J.K.; Anbazhagan, S.; Jayaprakash, V. Monoamine oxidase inhibitors: Perspective design for the treatment of depression and, neurological disorders. Curr. Enzym. Inhib., 2016, 12, 115-122.
[http://dx.doi.org/10.2174/1573408012666160402001715]
[9]
Mathew, B.; Parambi, D.G.T.; Mathew, G.E.; Uddin, M.S.; Inasu, S.T.; Kim, H. Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer’s and Parkinson’s diseases Arch. Pharm. Chem. Life Sci., 2019.e1900177
[http://dx.doi.org/10.1002/ardp.201900177]
[10]
Kabir, M.T.; Sufian, M.A.; Uddin, M.S.; Begum, M.M.; Akhter, S.; Islam, A.; Mathew, B.; Islam, M.S.; Amran, M.S.; Md Ashraf, G. NMDA receptor antagonists: Repositioning of emantine as multitargeting agent for Alzheimer’s therapy. Curr. Pharm. Des., 2019, 25(33), 3506-3518.
[http://dx.doi.org/10.2174/1381612825666191011102444] [PMID: 31604413]
[11]
Ramsay, R.R. Inhibitor design for monoamine oxidases. Curr. Pharm. Des., 2013, 19(14), 2529-2539.
[http://dx.doi.org/10.2174/1381612811319140004] [PMID: 23116392]
[12]
Mathew, B.; Suresh, J.; Anbazhagan, S.; Paulraj, J.; Krishnan, G.K. Heteroaryl chalcones: Mini review about their therapeutic voyage. BioMed. Prev. Nut., 2014, 4, 451-458.
[http://dx.doi.org/10.1016/j.bionut.2014.04.003]
[13]
Mathew, B.; Parambi, D.G.T.; Sivasankarapillai, V.S.; Uddin, M.S.; Suresh, J.; Mathew, G.E.; Joy, M.; Marathakam, A.; Gupta, S.V. Perspective design of chalcones for the management of CNS disorders. CNS Neurol. Disord. Drug Targets, 2019, 18(6), 432-445.
[http://dx.doi.org/10.2174/1871527318666190610111246] [PMID: 31187716]
[14]
Mathew, B.; Haridas, A.; Suresh, J.; Mathew, G.E.; Uçar, G.; Jayaprakash, V. Monoamine oxidase inhibitory actions of chalcones. A mini review. Cent. Nerv. Syst. Agents Med. Chem., 2016, 16(2), 120-136.
[http://dx.doi.org/10.2174/1871524915666151002124443] [PMID: 26429556]
[15]
Mathew, B. Unraveling the structural requirements of chalcone chemistry towards monoamine oxidase inhibition. Cent. Nerv. Syst. Agents Med. Chem., 2019, 19(1), 6-7.
[http://dx.doi.org/10.2174/1871524919666190131160122] [PMID: 30706795]
[16]
Mathew, B.; Mathew, G.E.; Uçar, G.; Baysal, I.; Suresh, J.; Vilapurathu, J.K.; Prakasan, A.; Suresh, J.K.; Thomas, A. Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies. Bioorg. Chem., 2015, 62, 22-29.
[http://dx.doi.org/10.1016/j.bioorg.2015.07.001] [PMID: 26189013]
[17]
Mathew, B.; Uçar, G.; Yabanoğlu-Çiftçi, S.; Baysal, I.; Suresh, J.; Mathew, G.E.; Vilapurathu, J.K.; Nadeena, A.M.; Nabeela, P.; Lakshmi, V.; Haridas, A.; Fathima, F. Development of fluorinated thienylchalcones as monoamine oxidase-b inhibitors: Design, synthesis, biological evaluation and molecular docking studies. Lett. Org. Chem., 2015, 12, 605-613.
[http://dx.doi.org/10.2174/1570178612666150903213416]
[18]
Mathew, B.; Mathew, G.E.; Uçar, G.; Baysal, I.; Suresh, J.; Mathew, S.; Haridas, A.; Jayaprakash, V. Potent and selective monoamine oxidase-b inhibitory activity: Fluoro- vs trifluoromethyl-4-hydroxylated chalcone derivatives. Chem. Biodivers., 2016, 13(8), 1046-1052.
[http://dx.doi.org/10.1002/cbdv.201500367] [PMID: 27402375]
[19]
Mathew, B.; Haridas, A.; Uçar, G.; Baysal, I.; Adeniyi, A.A.; Soliman, M.E.S.; Joy, M.; Mathew, G.E.; Lakshmanan, B.; Jayaprakash, V. Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors. Int. J. Biol. Macromol., 2016, 91, 680-695.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.05.110] [PMID: 27262516]
[20]
Mathew, B.; Haridas, A.; Uçar, G.; Baysal, I.; Joy, M.; Mathew, G.E.; Lakshmanan, B.; Jayaprakash, V. Synthesis, biochemistry, and computational studies of brominated thienyl chalcones: A new class of reversible MAO-B inhibitors. ChemMedChem, 2016, 11(11), 1161-1171.
[http://dx.doi.org/10.1002/cmdc.201600122] [PMID: 27159243]
[21]
Mathew, B.; Uçar, G.; Mathew, G.E.; Mathew, S.; Kalatharakkal Purapurath, P.; Moolayil, F.; Mohan, S.; Varghese Gupta, S. Monoamine oxidase inhibitory activity: Methyl- versus chloro-chalcone derivatives. ChemMedChem, 2016, 11(24), 2649-2655.
[http://dx.doi.org/10.1002/cmdc.201600497] [PMID: 27902880]
[22]
Sasidharan, R.; Manju, S.L.; Uçar, G.; Baysal, I.; Mathew, B. Identification of indole based chalcones: discovery of potent, selective and reversible class of MAO-B inhibitors. Arch. Pharm. (Weinheim), 2016, 349(8), 627-637.
[http://dx.doi.org/10.1002/ardp.201600088] [PMID: 27373997]
[23]
Mathew, B.; Uçar, G.; Raphael, C.; Mathew, G.E.; Joy, M.; Machaba, K.E. Characterization of thienylchalcones as hMAO-B inhibitors: Synthesis, biochemistry and molecular dynamics studies. ChemistrySelect, 2017, 2, 11113-11119.
[http://dx.doi.org/10.1002/slct.201702141]
[24]
Mathew, B.; Adeniyi, A.A.; Dev, S.; Joy, M.; Ucar, G.; Mathew, G.E.; Singh-Pillay, A.; Soliman, M.E. Pharmacophore based 3D-QSAR analysis of thienyl chalcone as new class of human MAO-B inhibitors. Investigation of combined quantum chemical and molecular dynamics approach. J. Phys. Chem. B, 2017, 121(6), 1186-1203.
[http://dx.doi.org/10.1021/acs.jpcb.6b09451] [PMID: 28084742]
[25]
Mathew, B.; Baek, S.C.; Parambi, D.G.T.; Lee, J.P.; Mathew, G.E.; Jayanthi, S.; Devaraji, D.; Raphael, C.; Vinod, D.; Kondarath, S.S.; Uddin, M.S.; Kim, H. Potent and highly selective dual-targeting monoamine oxidase-B inhibitors: Fluorinated chalcones of morpholine versus imidazole Arch.Pharm. Chem. Life Sci., 2019.e1800309
[26]
Parambi, D.G.T.; Oh, J.M.; Baek, S.C.; Lee, J.P.; Tondo, A.R.; Nicolotti, O.; Kim, H.; Mathew, B. Design, synthesis and biological evaluation of oxygenated chalcones as potent and selective MAO-B inhibitors. Bioorg. Chem., 2019, 93103335
[http://dx.doi.org/10.1016/j.bioorg.2019.103335] [PMID: 31606547]
[27]
Reeta.; Baek, S.C.; Lee, J.P.; Rangarajan, T.M.; Ayushee, Singh, R.P.; Singh, M.; Mangiatordi, G.F.; Nicolotti, O.; Kim, H.; Mathew, B. Ethyl acetohydroxamate incorporated chalcones: Unveiling a novel class of chalcones for multitarget monoamine oxidase-B inhibitors against Alzheimer’s disease. CNS Neurol. Dis. Drug Targets, 2019, 18, 643-654.
[28]
Sasidharan, R.; Sreedharannair Leelabaiamma, M.; Mohanan, R.; Jose, S.P.; Mathew, B.; Sukumaran, S. Anti-inflammatory effect of synthesized indole-based chalcone (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one: an in vitro and in vivo studies. Immunopharmacol. Immunotoxicol., 2019, 41(6), 568-576.
[http://dx.doi.org/10.1080/08923973.2019.1672177] [PMID: 31594421]
[29]
Chaves, O.A.; Sasidharan, R.; dos Santos de Oliveria, C.H.C.; Manju, S.L.; Joy, M.; Mathew, B.; Ferreira, J.C.N. In vitro study of the interaction between HSA and indolylchalcone, a potent human MAO-B inhibitor: Spectroscopic and molecular modeling studies. ChemistrySelect, 2019, 4, 1007-1014.
[http://dx.doi.org/10.1002/slct.201802665]
[30]
Oh, J.M.; Rangarajan, T.M.; Reeta, C.; Singh, R.P.; Singh, M.; Singh, R.P.; Kim, H. Novel class of chalcone oxime ethers as potent monoamine oxidase-B and acetylcholinesterase inhibitors. Molecules, 2020, 20, 2536.
[31]
Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Unnikrishnan, M.K.; Uddin, M.S.; Mathew, G.E.; Pratap, R.; Marathakam, A.; Mathew, B. Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules. Brain Res. Bull., 2020, 160, 121-140.
[http://dx.doi.org/10.1016/j.brainresbull.2020.03.018] [PMID: 32315731]
[32]
Cao, Z.; Yang, J.; Xu, R.; Song, Q.; Zhang, X.; Liu, H.; Qiang, X.; Li, Y.; Tan, Z.; Deng, Y. Design, synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment. Bioorg. Med. Chem., 2018, 26(5), 1102-1115.
[http://dx.doi.org/10.1016/j.bmc.2018.01.030] [PMID: 29409707]
[33]
Tian, C.; Qiang, X.; Song, Q.; Cao, Z.; Ye, C.; He, Y.; Deng, Y.; Zhang, L. Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer’s disease: Design, synthesis and biological evaluation. Bioorg. Chem., 2020, 94103477
[http://dx.doi.org/10.1016/j.bioorg.2019.103477] [PMID: 31818478]
[34]
Colović, M.B.; Krstić, D.Z.; Lazarević-Pašti, T.D.; Bondžić, A.M.; Vasić, V.M. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr. Neuropharmacol., 2013, 11(3), 315-335.
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[35]
Xiao, G.; Li, Y.; Qiang, X.; Xu, R.; Zheng, Y.; Cao, Z.; Luo, L.; Yang, X.; Sang, Z.; Su, F.; Deng, Y. Design, synthesis and biological evaluation of 4′-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease. Bioorg. Med. Chem., 2017, 25(3), 1030-1041.
[http://dx.doi.org/10.1016/j.bmc.2016.12.013] [PMID: 28011206]
[36]
Wang, L.; Wang, Y.; Tian, Y.; Shang, J.; Sun, X.; Chen, H.; Wang, H.; Tan, W. Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors. Bioorg. Med. Chem., 2017, 25(1), 360-371.
[http://dx.doi.org/10.1016/j.bmc.2016.11.002] [PMID: 27856236]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy