Sulfonamide Derivatives: Recent Compounds with Potent
Anti-alzheimer’s Disease Activity

Melford   Chuka   Egbujor
doi:10.2174/0118715249278489231128042135
Abstract

Facile synthetic procedures and broad spectrum of biological activities are special attributes of sulfonamides. Sulfonamide derivatives have demonstrated potential as a class of compounds for the treatment of Alzheimer's disease (AD). Recent sulfonamide derivatives have been reported as prospective anti-AD agents, with a focus on analogues that significantly inhibit the function of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and exhibit remarkable antioxidant and anti-inflammatory properties, all of which are critical for the treatment of AD. Sulfonamide- mediated activation of nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of the endogenous antioxidant response, has also been suggested as a potential therapeutic approach in AD. Additionally, it has been discovered that a number of sulfonamide derivatives show selectivity for the β- and γ-secretase enzymes and a significant reduction of amyloid B (Aβ) aggregation, which have been implicated in AD. The comparative molecular docking of benzenesulfonamide and donepezil, an AD reference drug showed comparable anti-AD activities. These suggest that sulfonamide derivatives may represent a new class of drugs for the treatment of AD. Thus, the current review will focus on recent studies on the chemical synthesis and evaluation of the anti-AD properties, molecular docking, pharmacological profile, and structure-activity relationship (SAR) of sulfonamide derivatives, as well as their potential anti-AD mechanisms of action. This paper offers a thorough assessment of the state of the art in this field of study and emphasizes the potential of sulfonamide derivatives synthesized during the 2012-2023 period as a new class of compounds for the treatment of AD.
Keywords: Sulfonamide derivatives, alzheimer disease, structure-activity relationship, molecular docking, NRF2, antioxidant.
« Previous Next »
Graphical Abstract

[1]
George, E.K.; Reddy, P.H. Can Healthy diets, regular Exercise, and better lifestyle delay the progress of dementia in elderly individuals? J. Alzheimers Dis.,  2019, 72(s1), S37-S58.
 [http://dx.doi.org/10.3233/JAD-190232]

[2]
Liang, C.S.; Li, D.J.; Yang, F.C.; Tseng, P.T.; Carvalho, A.F.; Stubbs, B.; Thompson, T.; Mueller, C.; Shin, J.I.; Radua, J.; Stewart, R.; Rajji, T.K.; Tu, Y.K.; Chen, T.Y.; Yeh, T.C.; Tsai, C.K.; Yu, C.L.; Pan, C.C.; Chu, C.S. Mortality rates in Alzheimer’s disease and non-Alzheimer’s dementias: A systematic review and meta-analysis. Lancet Healthy Longev.,  2021, 2(8), e479-e488.
 [http://dx.doi.org/10.1016/S2666-7568(21)00140-9] [PMID: 36097997]

[3]
Dementia.  Available from: https://www.who.int/en/newsroom/fact-sheets/detail/dementia

[4]
Price, M.; Ghercet, M.; Prina, M. The epidemiology and impact of dementia: Current state and future trends. WHO thematic briefing; World Health Organization, 2015, pp. 1-4.

[5]
Kim, D.H.; Yeo, S.H.; Park, J.M.; Choi, J.Y.; Lee, T.H.; Park, S.Y.; Ock, M.S.; Eo, J.; Kim, H.S.; Cha, H.J. Genetic markers for diagnosis and pathogenesis of Alzheimer’s disease. Gene,  2014, 545(2), 185-193.
 [http://dx.doi.org/10.1016/j.gene.2014.05.031] [PMID: 24838203]

[6]
Savelieff, M.G.; Lee, S.; Liu, Y.; Lim, M.H. Untangling amyloid-β tau, and metals in Alzheimer’s disease. ACS Chem. Biol.,  2013, 8(5), 856-865.
 [http://dx.doi.org/10.1021/cb400080f] [PMID: 23506614]

[7]
Blevins, H.; Xu, Y.; Biby, S.; Zhang, S. Mechanistic insights of
sulfonamide-based NLRP3 inhibitors for the treatment of neurodegenerative
diseases. FASEB J.,  2022, 36(S1), fasebj.2022.36.S1.R3734.
 [http://dx.doi.org/10.1096/fasebj.2022.36.S1.R3734]

[8]
Egbujor, M.C.; Garrido, J.; Borges, F.; Saso, L. Sulfonamide a valid scaffold for antioxidant drug development. Mini Rev. Org. Chem.,  2023, 20(2), 190-209.
 [http://dx.doi.org/10.2174/1570193X19666220411134006]

[9]
Egbujor, M.C.; Egu, S.A.; Okonkwo, V.I.; Jacob, A.D.; Egwuatu, P.I.; Amasiatu, I.S. Antioxidant drug design: Historical and decent developments. J. Pharm. Res. Int.,  2020, 32, 36-56.

[10]
Masand, N.; Gupta, S.P.; Khosa, R.L. N-substituted aryl sulphonamides as potential anti-alzheimer’s agents: Design, synthesis and biological evaluation. Curr. Computeraided Drug Des.,  2018, 14(4), 338-348.
 [http://dx.doi.org/10.2174/1573409914666180604115425] [PMID: 29866012]

[11]
Egbujor, M.C.; Okoro, U.C. New methionine-based p-toluenesulphonamoyl carboxamide derivatives as antimicrobial and antioxidant agents: Design, synthesis, and molecular docking. J. Pharm. Res. Int.,  2019, 28, 1-12.
 [http://dx.doi.org/10.9734/jpri/2019/v28i130192]

[12]
Egbujor, M.C.; Okoro, U.C.; Okafor, S.; Nwankwo, N.E. Design, synthesis and molecular docking of novel serine-based sulphonamide bioactive compounds as potential antioxidant and antimicrobial agents. Indo. Am. J. Pharm. Sci,  2019, 06(06), 12232-12240.

[13]
Egbujor, M.C.; Okoro, U.C.; Okafor, S.; Nwankwo, N.E. Synthesis, characterization and in silico studies of novel alkanoylated 4-methylphenyl sulphonamoyl carboxylic acids as potential antimicrobial and antioxidant agents. Int. J. Pharm. Phytopharmacol. Res,  2019, 9(3), 89-97.

[14]
Abdel-Aziz, A.A.M.; Angeli, A.; El-Azab, A.S.; Hammouda, M.E.A.; El-Sherbeny, M.A.; Supuran, C.T. Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions. Bioorg. Chem.,  2019, 84, 260-268.
 [http://dx.doi.org/10.1016/j.bioorg.2018.11.033] [PMID: 30508771]

[15]
Wan, Y.; Fang, G.; Chen, H.; Deng, X.; Tang, Z. Sulfonamide derivatives as potential anti-cancer agents and their SARs elucidation. Eur. J. Med. Chem.,  2021, 226113837
 [http://dx.doi.org/10.1016/j.ejmech.2021.113837] [PMID: 34530384]

[16]
Egbujor, M.C.; Okoro, U.C.; Okafor, S. Novel alanine based antimicrobial and antioxidant agents: Synthesis and molecular docking. Indian J. Sci. Technol.,  2020, 13(9), 1003-1014.
 [http://dx.doi.org/10.17485/ijst/2020/v013i09/146687]

[17]
Egbujor, M.C.; Okoro, U.C.; Okafor, S.N.; Amasiatu, I.S.; Amadi, U.B.; Egwuatu, P.I. Synthesis, molecular docking and pharmacological evaluation of new 4-methylphenylsulphamoyl carboxylic acids analogs. Int. J. Res. Pharm. Sci.,  2020, 11(4), 5357-5366.
 [http://dx.doi.org/10.26452/ijrps.v11i4.3157]

[18]
Egbujor, M.C.; Okoro, U.C.; Egu, S.A.; Egwuatu, P.I.; Eze, F.U.; Amasiatu, I.S. Synthesis and biological evaluation of alanine derived bioactive p-toluenesulphonamide analogs. Int. J. Res. Pharm. Sci.,  2020, 11(4), 6449-6458.
 [http://dx.doi.org/10.26452/ijrps.v11i4.3440]

[19]
Jain, A.N.; Nicholls, A. Recommendations for evaluation of computational methods. J. Comput. Aided Mol. Des.,  2008, 22(3-4), 133-139.
 [http://dx.doi.org/10.1007/s10822-008-9196-5] [PMID: 18338228]

[20]
Broks, J.S.; Harvey, R.J. Donepezil for dementia due to alzheimer’s disease. Cochrane. Database of Systematic Reviews,  2018, 6,.

[21]
Zanforlin, E.; Zagotto, G.; Ribaudo, G. An overview of new possible treatments of Alzheimer’s disease, based on natural products and semisynthetics compounds. Curr. Med. Chem.,  2017, 24(34), 3749-3773.
 [PMID: 28707586]

[22]
Briggs, R.; Kennelly, S.P.; O’Neill, D. Drug treatments in Alzheimer’s disease. Clin. Med.,  2016, 16(3), 247-253.
 [http://dx.doi.org/10.7861/clinmedicine.16-3-247] [PMID: 27251914]

[23]
Aisen, P.S. The development of anti-amyloid therapy for Alzheimer’s disease: From secretase modulators to polymerisation inhibitors. CNS Drugs,  2005, 19(12), 989-996.
 [http://dx.doi.org/10.2165/00023210-200519120-00002] [PMID: 16332141]

[24]
Robinson, S.R.; Bishop, G.M.; Lee, H.; Münch, G. Lessons from the AN 1792 Alzheimer vaccine: Lest we forget. Neurobiol. Aging,  2004, 25(5), 609-615.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2003.12.020] [PMID: 15172738]

[25]
Wischik, C.M.; Staff, R.T.; Wischik, D.J.; Bentham, P.; Murray, A.D.; Storey, J.M.D.; Kook, K.A.; Harrington, C.R. Tau aggregation inhibitor therapy: An exploratory phase 2 study in mild or moderate Alzheimer’s disease. J. Alzheimers Dis.,  2015, 44(2), 705-720.
 [http://dx.doi.org/10.3233/JAD-142874] [PMID: 25550228]

[26]
Tougu, V. Acetylcholinesterase: Mechanism of catalysis and inhibition. Curr. Med. Chem.,  2001, 1(1), 155-170.

[27]
Cygler, M.; Schrag, J.D.; Sussman, J.L.; Harel, M.; Silman, I.; Gentry, M.K.; Doctor, B.P. Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins. Protein Sci.,  1993, 2(3), 366-382.
 [http://dx.doi.org/10.1002/pro.5560020309] [PMID: 8453375]

[28]
Khansari, N.; Shakiba, Y.; Mahmoudi, M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat. Inflamm. Allergy Drug Discov.,  2009, 3(1), 73-80.
 [http://dx.doi.org/10.2174/187221309787158371] [PMID: 19149749]

[29]
Apiraksattayakul, S.; Pingaew, R.; Prachayasittikul, V.; Ruankham, W.; Jongwachirachai, P.; Songtawee, N.; Suwanjang, W.; Tantimongcolwat, T.; Prachayasittikul, S.; Prachayasittikul, V.; Phopin, K. Neuroprotective properties of bis-sulfonamide derivatives against 6-ohda-induced parkinson’s model via sirtuin 1 activity and in silico pharmacokinetic properties. Front. Mol. Neurosci.,  2022, 15890838
 [http://dx.doi.org/10.3389/fnmol.2022.890838] [PMID: 35935335]

[30]
Osama, A.; Zhang, J.; Yao, J.; Yao, X.; Fang, J. Nrf2: a dark horse in Alzheimer’s disease treatment. Ageing Res. Rev.,  2020, 64101206
 [http://dx.doi.org/10.1016/j.arr.2020.101206] [PMID: 33144124]

[31]
Egbujor, M.C.; Saha, S.; Buttari, B.; Profumo, E.; Saso, L. Activation of Nrf2 signaling pathway by natural and synthetic chalcones: a therapeutic road map for oxidative stress. Expert Rev. Clin. Pharmacol.,  2021, 14(4), 465-480.
 [http://dx.doi.org/10.1080/17512433.2021.1901578] [PMID: 33691555]

[32]
Egbujor, M.C.; Buttari, B.; Profumo, E.; Telkoparan-Akillilar, P.; Saso, L. An overview of nrf2-activating compounds bearing α,β-unsaturated moiety and their antioxidant effects. Int. J. Mol. Sci.,  2022, 23(15), 8466.
 [http://dx.doi.org/10.3390/ijms23158466] [PMID: 35955599]

[33]
Egbujor, M.C.; Tucci, P.; Onyeije, U.C.; Emeruwa, C.N.; Saso, L. NRF2 activation by nitrogen heterocycles: A review. Molecules,  2023, 28(6), 2751.
 [http://dx.doi.org/10.3390/molecules28062751] [PMID: 36985723]

[34]
Egbujor, M.C.; Petrosino, M.; Zuhra, K.; Saso, L. The role of organosulfur compounds as Nrf2 activators and their antioxidant effects. Antioxidants,  2022, 11(7), 1255.
 [http://dx.doi.org/10.3390/antiox11071255] [PMID: 35883746]

[35]
Supuran, C.T.; Scozzafava, A.; Menabuoni, L.; Mincione, F.; Briganti, F.; Mincione, G. Carbonic anhydrase inhibitors. Part 71. Eur. J. Pharm. Sci.,  1999, 8(4), 317-328.
 [http://dx.doi.org/10.1016/S0928-0987(99)00022-6] [PMID: 10425382]

[36]
Egbujor, M.C.; Okoro, U.C.; Okafor, S. Design, synthesis, molecular docking, antimicrobial, and antioxidant activities of new phenylsulfamoyl carboxylic acids of pharmacological interest. Med. Chem. Res.,  2019, 28(12), 2118-2127.
 [http://dx.doi.org/10.1007/s00044-019-02440-3]

[37]
Davies, T.Q.; Tilby, M.J.; Skolc, D.; Hall, A.; Willis, M.C. Primary sulfonamide synthesis using the sulfinylamine reagent N-sulfinylo-(tertbutyl) hydroxylamine, t-Buonso. Org. Lett.,  2020, 22(24), 9495-9499.
 [http://dx.doi.org/10.1021/acs.orglett.0c03505] [PMID: 33237777]

[38]
Egbujor, M.C.; Okoro, U.C.; Egu, A.S.; Okonkwo, V.I.; Okafor, S.N.; Emeruwa, C.N.; Egwuatu, P.I.; Umeh, O.R.; Eziafakaego, M.I.; Amasiatu, I.S.; Nwobodo, D.C. Synthesis and biological evaluation of sulfamoyl carboxamide derivatives from sulfur-containing α-amino acids. Healing Khana Witthayasat Maha Witthayalai Chiang Mai,  2022, 49(4), 1100-1115.
 [http://dx.doi.org/10.12982/CMJS.2022.070]

[39]
Egbujor, M.; Okafor, S.N.; Okoro, U.C.; Egu, S.; Amasiatu, I.; Egwuatu, P.; Umeh, O.; Ibo, E. Design, synthesis, and molecular docking of cysteine-based sulphonamide derivatives as antimicrobial agents. Res. Pharm. Sci.,  2022, 17(1), 99-110.
 [http://dx.doi.org/10.4103/1735-5362.329930] [PMID: 34909048]

[40]
Dakhlaoui, I.; Bernard, P.J.; Pietrzak, D.; Simakov, A.; Maj, M.; Refouvelet, B.; Béduneau, A.; Cornu, R.; Jozwiak, K.; Chabchoub, F.; Iriepa, I.; Martin, H.; Marco-Contelles, J.; Ismaili, L. Exploring the potential of sulfonamide -dihyldropyridine hybrids as multitargeted ligand for Alzheimer’s disease treatment. Int. J. Mol. Sci.,  2023, 24(11), 9742.
 [http://dx.doi.org/10.3390/ijms24119742] [PMID: 37298693]

[41]
Benchekroun, M.; Romero, A.; Egea, J.; León, R.; Michalska, P.; Buendía, I.; Jimeno, M.L.; Jun, D.; Janockova, J.; Sepsova, V.; Soukup, O.; Bautista-Aguilera, O.M.; Refouvelet, B.; Ouari, O.; Marco-Contelles, J.; Ismaili, L. The antioxidant additive approach for Alzheimer’s disease therapy. New ferulic (Lipoic) acid plus melatomin modified tacrines as cholinesterases inhibitors, direct antioxidants, and nuclear factor (erythroid-dervived 2) - like 2 activators. J. Med. Chem.,  2016, 59(21), 9967-9973.
 [http://dx.doi.org/10.1021/acs.jmedchem.6b01178] [PMID: 27736061]

[42]
Khan, S.; Ullah, H.; Taha, M.; Rahim, F.; Sarfraz, M.; Iqbal, R.; Iqbal, N.; Hussain, R.; Ali Shah, S.A.; Ayub, K.; Albalawi, M.A.; Abdelaziz, M.A.; Alatawi, F.S.; Khan, K.M. Synthesis, DFT studies molecular docking and biological activity evaluation of thiazole -sulfonamide derivatives as potent Alzheimer’s inhibitors. Molecules,  2023, 28(2), 559.
 [http://dx.doi.org/10.3390/molecules28020559] [PMID: 36677616]

[43]
Fortin, J.S.; Shimanaka, K.; Saraswati, A.P. M, Liu; Wang, K-W.; Hagar, H-T.; Maity, S.; Ganegamage, S.K.; Ellsworth, E.; Counts, S.E; Borhan, B.; Dttmer, B.; Kuo, M-H. Anti-fibrillization effects of sulfonamide derivatives on synuclein and hyperphosph orylated tau isoform 1N4R. J. Mol. Struct.,  2022, 05, 1267.

[44]
Ganeshpurkar, A.; Singh, R.; Kumar, D.; Gore, P.; Shivhare, S.; Sardana, D.; Rayala, S.; Kumar, A.; Singh, S.K. Identification of sulfonamide based butyrylcholinesterase inhibitors through scaffold hopping approach. Int. J. Biol. Macromol.,  2022, 203, 195-211.
 [http://dx.doi.org/10.1016/j.ijbiomac.2022.01.136] [PMID: 35090939]

[45]
Taha, M.; Alshamrani, F.J.; Rahim, F.; Anouar, E.H.; Uddin, N.; Chigurupati, S.; Almandil, N.B.; Farooq, R.K.; Iqbal, N.; Aldubayan, M.; Venugopal, V.; Khan, K.M. Synthesis, characterization, biological evaluation, and kinetic study of indole base sulfonamide derivatives as acetylcholinesterase inhibitors in search of potent anti-Alzheimer agent. J. King Saud Univ. Sci.,  2021, 33(3)101401
 [http://dx.doi.org/10.1016/j.jksus.2021.101401]

[46]
Kumar, A.; Gupta, V.; Sharma, S. Donepezil.Stat Pearls; Stat Pearls publishing: Internet Treasure Island, FL, 2021. 

[47]
Queda, F. Calos; Gwizdala, K.; Magalhaes, J.D.; Cardoso, S.M.; Chaves, S.; Piemontese, L.; Santos, M.A. Novel donepezil - arylsulfonamide hybrids as multitargeted -directed ligands for potential treatment of Alzheimer’s disease. Molecules,  2021, 26, 1658.
 [http://dx.doi.org/10.3390/molecules26061658] [PMID: 33809771]

[48]
Gök, N.; Akıncıoğlu, A.; Erümit Binici, E.; Akıncıoğlu, H.; Kılınç, N.; Göksu, S. Synthesis of novel sulfonamides with anti-Alzheimer and antioxidant capacities. Arch. Pharm.,  2021, 354(7)2000496
 [http://dx.doi.org/10.1002/ardp.202000496]

[49]
Li, N.; Wang, Y.; Li, W.; Li, H.; Yang, L.; Wang, J.; Mahdy, H.A.; Mehany, A.B.M.; Jaiash, D.A.; Santali, E.Y.; Eissa, I.H. Screening of some sulfonamide and sulfonylurea derivatives as anti-Alzherimer’s agents targeting BACE1 and PPAR. J. Chem.,  2020, 2020, 1-17.

[50]
Lolak, N.; Boga, M.; Tuneg, M.; Karakoc, G.; Akocak, S.; Supuran, C.T. Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile. J. Enzyme Inhib. Med. Chem.,  2020, 35(1), 424-431.
 [http://dx.doi.org/10.1080/14756366.2019.1707196] [PMID: 31899985]

[51]
de Souza, M.M.; Andreolla, M.C.; Ribeiro, T.C.; Gonçalves, A.E.; Medeiros, A.R.; de Souza, A.S.; Ferreira, L.L.G.; Andricopulo, A.D.; Yunes, R.A.; de Oliveira, A.S. Structure-activity relationships of sulfonamides derived from carvacrol and their potential for the treatment of Alzheimer’s disease. RSC Med. Chem.,  2020, 11(2), 307-316.
 [http://dx.doi.org/10.1039/D0MD00009D] [PMID: 33479638]

[52]
Wei, H.; Zhang, H-L.; Wang, X-C.; Xie, J-Z.; An, D-D.; Wan, L.; Wang, J-Z.; Zeng, Y.; Shu, X-J.; Westermarck, J.; Lu, Y-M.; Ohlmeyer, M.; Liu, R. Direct activation of protein phosphate 2A (PP2A) by tricylic sulfonamides ameliorates Alzheimer’s diseases pathogenesis in cell and animal models. Neurother,  2020, 17, 1087-1103.
 [http://dx.doi.org/10.1007/s13311-020-00841-6] [PMID: 32096091]

[53]
Swetha, R.; Kumar, D.; Gupta, S.K.; Ganeshpurkar, A.; Singh, R.; Gutti, G.; Kumar, D.; Jana, S.; Krishnamurthy, S.; Singh, S.K. Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer’s disease. Future Med. Chem.,  2019, 11(24), 3161-3178.
 [http://dx.doi.org/10.4155/fmc-2019-0106] [PMID: 31838895]

[54]
Akocak, S.; Boga, M.; Lolak, N.; Tuneg, M.; Sanku, R.K.K. Design, synthesis and biological evaluation of 1,3-diaryltriazenesubstituted sulfonamides as antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitors. J. Turk. Chem. Soc.,  2019, 6(1), 63-70.
 [http://dx.doi.org/10.18596/jotcsa.516444]

[55]
Ulus, R.; Esirden, İ.; Aday, B.; Turgut, G.Ç.; Şen, A.; Kaya, M. Synthesis of novel acridine-sulfonamide hybrid compounds as acetylcholinesterase inhibitor for the treatment of alzheimer’s disease. Med. Chem. Res.,  2018, 27(2), 634-641.
 [http://dx.doi.org/10.1007/s00044-017-2088-2]

[56]
Mutahir, S.; Jonczyk, J.; Bajda, M.; Khan, I.U.; Khan, M.S.; Ullah, N.; Ashraf, M.; Qurat-ul-Ani; Raiz, S.; Hussain, S.; Yar, M. Novel biphenyl bis-sulfonamides as acetyl and butyrylcholinesterase inhibitors: Synthesis, biological evaluation and molecular modeling stuies. Bioorg. Chem.,  2016, 64, 13-20.
 [http://dx.doi.org/10.1016/j.bioorg.2015.11.002] [PMID: 26595185]

[57]
Bag, S.; Tulsan, R.; Sood, A.; Cho, H.; Redjeb, H.; Zhou, W.; LeVine, H., III; Török, B.; Török, M. Sulfonamides as multifunctional agents for Alzheimer’s disease. Bioorg. Med. Chem. Lett.,  2015, 25(3), 626-630.
 [http://dx.doi.org/10.1016/j.bmcl.2014.12.006] [PMID: 25537270]

[58]
Riaz, S.; Khan, I.U.; Bajda, M.; Ashraf, M. Qurat -ul-Ani; A, Shaukat; Rehman, T.U.; Mutahir, S.; Hussain, S.; Mustafa, G.; Yar, M. Pyridine sulfonamide as a small key organic molecular for the potential treatment of type II- diabetes mellitus and Alzheimer’s disease: In vitro studies against yeast. Bioorg. Chem.,  2015, 63, 64-71.
 [http://dx.doi.org/10.1016/j.bioorg.2015.09.008] [PMID: 26451651]

[59]
Abbasi, M.A.; Ahamd, S. Aziz-ur-Rahmar; Rasool, S.; Khan, K.M; Ashraf, M.; Nasar, R; Ismail, T. Sulfonamide derivatives of 2-amino - phyenlyethane as suitable cholinesterase inhibitors. Trop. J. Pharm. Res.,  2014, 13, 737-745.
 [http://dx.doi.org/10.4314/tjpr.v13i5.13]

[60]
Göçer, H.; Akıncıoğlu, A.; Öztaşkın, N.; Göksu, S.; Gülçin, İ. Synthesis, antioxidant, and antiacetylcholinesterase activities of sulfonamide derivatives of dopamine-related compounds. Arch. Pharm.,  2013, 346(11), 783-792.
 [http://dx.doi.org/10.1002/ardp.201300228] [PMID: 24591156]

[61]
Aziz-ur-Rehman; Afroz, S.; Abassi, M.A.; Tanveer, W.; Khan, K.M.; Ashraf, M.; Ahmad, I.; Afzal, I.; Ambreen, N. Synthesis, characterization and biological screening of sulfonamides derived from 2-phenylethylamine. Pak. J. Pharm. Sci.,  2012, 25, 809-814.

[62]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem.,  2010, 31(2), 455-461.
 [http://dx.doi.org/10.1002/jcc.21334] [PMID: 19499576]

[63]
Schrödinger, L.; DeLano, W. PyMOL., 2020. Retrieved from: http://www.pymol.org/pymol

[64]
Xue, Q.; Liu, X.; Russell, P.; Li, J.; Pan, W.; Fu, J.; Zhang, A. Evaluation of the binding performance of flavonoids to estrogen receptor alpha by Autodock, Autodock Vina and Surflex-Dock. Ecotoxicol. Environ. Saf.,  2022, 233113323
 [http://dx.doi.org/10.1016/j.ecoenv.2022.113323] [PMID: 35183811]

[65]
Kitchen, D.B.; Decornez, H.; Furr, J.R.; Bajorath, J. Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat. Rev. Drug Discov.,  2004, 3(11), 935-949.
 [http://dx.doi.org/10.1038/nrd1549] [PMID: 15520816]

[66]
Nittinger, E.; Inhester, T.; Bietz, S.; Meyder, A.; Schomburg, K.T.; Lange, G.; Klein, R.; Rarey, M. Large-scale analysis of hydrogen bond interaction patterns in protein-ligand interfaces. J. Med. Chem.,  2017, 60(10), 4245-4257.
 [http://dx.doi.org/10.1021/acs.jmedchem.7b00101] [PMID: 28497966]

[67]
Gohlke, H.; Klebe, G. Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors. Angew. Chem. Int. Ed.,  2002, 41(15), 2644-2676.
 [http://dx.doi.org/10.1002/1521-3773(20020802)41:15<2644:AID-ANIE2644>3.0.CO;2-O] [PMID: 12203463]

[68]
Dobberschütz, S.; Rimmen, M.; Hassenkam, T.; Andersson, M.P.; Stipp, S.L.S. Specific ion effects on the hydrophobic interaction of benzene self-assembled monolayers. Phys. Chem. Chem. Phys.,  2015, 17(33), 21432-21441.
 [http://dx.doi.org/10.1039/C5CP01803J] [PMID: 26220291]

[69]
Pérez, V.; Marco, J.L.; Fernández-Álvarez, E.; Unzeta, M. Relevance of benzyloxy group in 2-indolyl methylamines in the selective MAO-B inhibition. Br. J. Pharmacol.,  1999, 127(4), 869-876.
 [http://dx.doi.org/10.1038/sj.bjp.0702600] [PMID: 10433493]

[70]
Lane, R.M.; Potkin, S.G.; Enz, A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int. J. Neuropsychopharmacol.,  2006, 9(1), 101-124.
 [http://dx.doi.org/10.1017/S1461145705005833] [PMID: 16083515]

[71]
García-Ayllón, M.S.; Small, D.H.; Avila, J.; Sáez-Valero, J. Revisiting the role of acetylcholinesterase in Alzheimer’s disease: cross-talk with P-tau and β-amyloid. Front. Mol. Neurosci.,  2011, 4(22), 22.
 [http://dx.doi.org/10.3389/fnmol.2011.00022] [PMID: 21949503]

[72]
Marucci, G.; Buccioni, M.; Ben, D.D.; Lambertucci, C.; Volpini, R.; Amenta, F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology,  2021, 190108352
 [http://dx.doi.org/10.1016/j.neuropharm.2020.108352] [PMID: 33035532]

[73]
Jiang, C.S.; Ge, Y.X.; Cheng, Z.Q.; Wang, Y.Y.; Tao, H.R.; Zhu, K.; Zhang, H. Discovery of new selective butyrylcholinesterase (BChE) inhibitors with anti-Aβ aggregation activity: Structure-based virtual screening, hit optimization and biological evaluation. Molecules,  2019, 24(14), 2568.
 [http://dx.doi.org/10.3390/molecules24142568] [PMID: 31311169]

[74]
Sawhney, S.K.; Singh, M. Molecular docking software’s applications and basic challenges faced: A review. Int. Res. J. Pharm.,  2020, 11(2), 15-19.
 [http://dx.doi.org/10.7897/2230-8407.110213]

[75]
Ewing, T.J.A.; Makino, S.; Skillman, A.G.; Kuntz, I.D. DOCK 4.0: search strategies for automated molecular docking of flexible molecule databases. J. Comput. Aided Mol. Des.,  2001, 15(5), 411-428.
 [http://dx.doi.org/10.1023/A:1011115820450] [PMID: 11394736]

[76]
Özer, E.Ö.; Tan, O.U.; Ozadali, K.; Küçükkılınç, T.; Balkan, A.; Uçar, G. Synthesis, molecular modeling and evaluation of novel N'-2-(4-benzylpiperidin-/piperazin-1-yl) acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation. Bioorg Med Chem Lett,  2013, 23(2), 440-443.; 
Plemontese, L.; Tomas, D.; Hiremathad, A.; Capriati, V.; Candeias, E.; Cardoso, S.M.; Chaves, S.; Santos, M.A. Donepezil structure-based hybrids as potential multifunctional anti-alzheimer’s drug candidates. J. Enzyme Inhib. Med. Chem.,  2018, 33, 1212-1224.

[77]
Costanzo, P.; Cariati, L.; Desiderio, D.; Sgammato, R.; Lamberti, A.; Arcone, R.; Salerno, R.; Nardi, M.; Masullo, M.; Oliverio, M. Design, synthesis and evaluation of donepezil-like compounds as AChE and BACE-1 inhibitors. ACS Med. Chem. Lett.,  2016, 7(5), 470-475.
 [http://dx.doi.org/10.1021/acsmedchemlett.5b00483] [PMID: 27190595]

[78]
Kareem, R.T.; Abedinifar, F.; Mahmood, E.A.; Ebadi, A.G.; Rajabi, F.; Vessally, E. The recent development of donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s agents: Highlights from 2010 to 2020. RSC Advances,  2021, 11(49), 30781-30797.
 [http://dx.doi.org/10.1039/D1RA03718H] [PMID: 35498922]

[79]
Dias Viegas, F.P.; de Freitas Silva, M.; Divino da Rocha, M.; Castelli, M.R.; Riquiel, M.M.; Machado, R.P.; Vaz, S.M.; Simões de Lima, L.M.; Mancini, K.C.; Marques de Oliveira, P.C.; Morais, É.P.; Gontijo, V.S.; da Silva, F.M.R.; D’Alincourt da Fonseca Peçanha, D.; Castro, N.G.; Neves, G.A.; Giusti-Paiva, A.; Vilela, F.C.; Orlandi, L.; Camps, I.; Veloso, M.P.; Leomil Coelho, L.F.; Ionta, M.; Ferreira-Silva, G.Á.; Pereira, R.M.; Dardenne, L.E.; Guedes, I.A.; de Oliveira Carneiro Junior,  W.; Quaglio Bellozi, P.M.; Pinheiro de Oliveira, A.C.; Ferreira, F.F.; Pruccoli, L.; Tarozzi, A.; Viegas, C. Jr Design, synthesis and pharmacological evaluation of N -benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates. Eur. J. Med. Chem.,  2018, 147, 48-65.
 [http://dx.doi.org/10.1016/j.ejmech.2018.01.066] [PMID: 29421570]

[80]
Bitencourt-Ferreira, G.; Veit-Acosta, M.; de Azevedo, W.F., Jr Hydrogen bonds in protein-ligand complexes. Methods Mol. Biol.,  2019, 2053, 93-107.
 [http://dx.doi.org/10.1007/978-1-4939-9752-7_7] [PMID: 31452101]

[81]
Zhao, H.; Huang, D. Hydrogen bonding penalty upon ligand binding. PLoS One,  2011, 6(6)e19923
 [http://dx.doi.org/10.1371/journal.pone.0019923] [PMID: 21698148]

[82]
Wu, M.Y.; Dai, D.Q.; Yan, H. PRL-dock: Protein-ligand docking based on hydrogen bond matching and probabilistic relaxation labeling. Proteins,  2012, 80(9), 2137-2153.
 [http://dx.doi.org/10.1002/prot.24104] [PMID: 22544808]

[83]
Lima, C.C.; Silva, D.S.N.; De Sa, E.R.A. computational analysis of sulfonamide - based compounds by molecular docking and ADME/T in the inhibition of acetylcholinesterase (AChE) in Alzheimer’s disease. Open Acess Library J.,  2022, 9e8469

[84]
Tsantili-Kakoulidou, A.; Demopoulos, V. Drug-like properties and fraction lipophilicity index as a combined metric. ADMET DMPK,  2021, 9(3), 177-190.
 [http://dx.doi.org/10.5599/admet.1022] [PMID: 35300360]

[85]
Benet, L.Z.; Hosey, C.M.; Ursu, O.; Oprea, T.I. BDDCS, the Rule of 5 and drugability. Adv. Drug Deliv. Rev.,  2016, 101, 89-98.
 [http://dx.doi.org/10.1016/j.addr.2016.05.007] [PMID: 27182629]

[86]
Adessi, C.; Frossard, M.J.; Boissard, C.; Fraga, S.; Bieler, S.; Ruckle, T.; Vilbois, F.; Robinson, S.M.; Mutter, M.; Banks, W.A.; Soto, C. Pharmacological profiles of peptide drug candidates for the treatment of Alzheimer’s disease. J. Biol. Chem.,  2003, 278(16), 13905-13911.
 [http://dx.doi.org/10.1074/jbc.M211976200] [PMID: 12578830]

[87]
Hogan, D.B. Progress update: Pharmacological treatment of Alzheimer’s disease. Neuropsychiatr. Dis. Treat.,  2007, 3(5), 569-578.
 [PMID: 19300586]

[88]
Conti Filho, C.E.; Loss, L.B.; Marcolongo-Pereira, C.; Rossoni, J.V., Junior; Barcelos, R.M.; Chiarelli-Neto, O.; Silva, B.S.; Passamani Ambrosio, R.; Castro, F.C.A.Q.; Teixeira, S.F.; Mezzomo, N.J. Advances in Alzheimer’s disease’s pharmacological treatment. Front. Pharmacol.,  2023, 141101452
 [http://dx.doi.org/10.3389/fphar.2023.1101452] [PMID: 36817126]

[89]
Giubilei, F. Beyond cholinesterase inhibition: Anti-inflammatory role and pharmacological profile of current drug therapy for Alzheimer’s disease. CNS Neurol. Disord. Drug Targets,  2016, 15(6), 683-689.
 [http://dx.doi.org/10.2174/1871527315666160518122917] [PMID: 27189472]

[90]
Huang, L.K.; Chao, S.P.; Hu, C.J. Clinical trials of new drugs for Alzheimer disease. J. Biomed. Sci.,  2020, 27(1), 18.
 [http://dx.doi.org/10.1186/s12929-019-0609-7] [PMID: 31906949]

[91]
Ganeshpurkar, A.; Singh, R.; Tripathi, P.; Alam, Q.; Krishnamurthy, S.; Kumar, A.; Singh, S.K. Effect of sulfonamide derivatives of phenylglycine on scopolamine-induced amnesia in rats. Ibrain,  2023, 9(1), 13-31.
 [http://dx.doi.org/10.1002/ibra.12092] [PMID: 37786521]

[92]
Lu, D.; Chambers, P.; Wipf, P.; Xie, X.Q.; Englert, D.; Weber, S. Lipophilicity screening of novel drug-like compounds and comparison to clogP. J. Chromatogr. A,  2012, 1258, 161-167.
 [http://dx.doi.org/10.1016/j.chroma.2012.07.078] [PMID: 22939208]

[93]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3-25. 1. Adv. Drug Deliv. Rev.,  2001, 46(1-3), 3-26.
 [http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]

[94]
Veber, D.F.; Johnson, S.R.; Cheng, H.Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem.,  2002, 45(12), 2615-2623.
 [http://dx.doi.org/10.1021/jm020017n] [PMID: 12036371]

[95]
Van de waterbeemd, H.; Carter, R.E.; Grassy, G.; Kubinyi, H.; Martins, Y.C.; Tute, M.S.; Willet, P. Grossory of terms used in
computational drug design 1997, 69(5), 1137-1152.

[96]
Guha, R. On exploring structure-activity relationships. Methods Mol. Biol.,  2013, 993, 81-94.
 [http://dx.doi.org/10.1007/978-1-62703-342-8_6] [PMID: 23568465]

[97]
McKinney, J.D.; Richard, A.; Wallero, C.; Newman, M.C.; Gerberick, F. The practice of structure activity relationships (SAR) in toxicology. Toxicol. Sci.,  2000, 56(1), 8-17.
 [http://dx.doi.org/10.1093/toxsci/56.1.8]

[98]
Dighe, S.N.; Deora, G.S.; De la Mora, E.; Nachon, F.; Chan, S.; Parat, M.O.; Brazzolotto, X.; Ross, B.P. Discovery and structure-activity relationships of a highly selective butyrylcholinesterase inhibitor by structure-based virtual screening. J. Med. Chem.,  2016, 59(16), 7683-7689.
 [http://dx.doi.org/10.1021/acs.jmedchem.6b00356] [PMID: 27405689]

[99]
Ansari, F.; Ghasemi, J.B.; Niazi, A. Three dimensional quantitative structure activity relationship and pharmacophore modeling of tacrine derivatives as acetylcholinesterase inhibitors in Alzheimer’s treatment. Med. Chem.,  2020, 16(2), 155-168.
 [http://dx.doi.org/10.2174/1573406415666190513100646] [PMID: 31092184]

[100]
Tong, W.; Welsh, W.J.; Shi, L.; Fang, H.; Perkins, R. Structure-activity relationship approaches and applications. Environ. Toxicol. Chem.,  2003, 22(8), 1680-1695.
 [http://dx.doi.org/10.1897/01-198] [PMID: 12924570]
Rights & Permissions Print Cite
Article Metrics
40
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0118715249278489231128042135	Print ISSN 1871-5249
Publisher Name Bentham Science Publisher	Online ISSN 1875-6166
Central Nervous System Agents in Medicinal Chemistry

Sulfonamide Derivatives: Recent Compounds with Potent Anti-alzheimer’s Disease Activity

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles
