Design and synthesis of new indole drug candidates to treat Alzheimer’s disease and targeting neuro-inflammation using a multi-target-directed ligand (MTDL) strategy

References

• Yao Z, Li-Yun Z, Yu-Ren J, et al. Design, synthesis and biological evaluation of dual acetylcholinesterase and phosphodiesterase 5A inhibitors in treatment for Alzheimer’s disease. Bioorg Med Chem Lett. 2017;27(17):4180–4184.
   PubMed Web of Science ®Google Scholar
• Gerard AKT, Jacques J, Sarel FM. Tacrine, trolox and tryptoline as lead compounds for the design and synthesis of multi-target agents for Alzheimer’s disease therapy. Open Med Chem J. 2017;11:24–37.
   PubMedGoogle Scholar
• Luo Z, Sheng J, Sun Y, Lu C, Yan J, Liu A, Luo H-B, Huang L, Li X. Synthesis and evaluation of multi-target-directed ligands against Alzheimer’s disease based on the fusion of donepezil and ebselen. J Med Chem. 2013;56(22):9089–9099.
   PubMed Web of Science ®Google Scholar
• Zhipei S, Keren W, Ping B, et al. Design, synthesis and biological evaluation of novel O-carbamoyl ferulamide derivatives as multi-target-directed ligands for the treatment of Alzheimer’s disease. Eur J Med Chem. 2020;194:112265–112289.
   PubMed Web of Science ®Google Scholar
• Yuying F, Wenjuan X, Bao C, et al. Design, synthesis, and biological evaluation of compounds with a new scaffold as anti-neuroinflammatory agents for the treatment of Alzheimer’s disease. Eur J Med Chem. 2018;149:129–138.
   PubMed Web of Science ®Google Scholar
• Lei F, Birgit K, Jochen L, et al. Michael, design and synthesis of tacrine–ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates. Bioorg Med Chem Lett. 2008;18:2905–2909.
   PubMed Web of Science ®Google Scholar
• Ferreira JPS, Albuquerque HMT, Cardoso SM, Silva AMS, Silva VLM. Dual-target compounds for Alzheimer’s disease: natural and synthetic AChE and BACE-1 dualinhibitors and their structure-activity relationship (SAR). Eur J Med Chem. 2021;221:113492–113518.
   PubMed Web of Science ®Google Scholar
• Tanzeel UR, Islam UK, Muhammad A, et al. An efficient synthesis of bi-aryl pyrimidine heterocycles: potential new drug candidates to treat Alzheimer’s Disease. Arch Pharm Chem Life Sci. 2017;350:1600304–1600315.
   Web of Science ®Google Scholar
• El-Sayed NAE, Farag AES, Ezzat MAF, Akincioglu H, Gülçin İ, Abou-Seri SM. Design, synthesis, in vitro and in vivo evaluation of novel pyrrolizine-based compounds with potential activity as cholinesterase inhibitors and anti-Alzheimer’s agents. Bioorg Chem. 2019;93:103312–103325.
   PubMed Web of Science ®Google Scholar
• Liao Q, Li Q, Zhao Y, Jiang P, Yan Y, Sun H, Liu W, Feng F, Qu W. Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer’s disease. Bioorg Chem. 2020;99:103844–103857.
   PubMed Web of Science ®Google Scholar
• Salehi N, Mirjalili BBF, Nadri H, Abdolahi Z, Forootanfar H, Samzadeh-Kermani A, Küçükkılınç TT, Ayazgok B, Emami S, Haririan I, et al. Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer’s agents. Bioorg Chem. 2019;83:559–568.
   PubMed Web of Science ®Google Scholar
• Van der ZEA, Platt B, Riedel G. Acetylcholine: future research and perspectives. Behav Brain Res. 2011;221(2):583–586.
   PubMed Web of Science ®Google Scholar
• Zhou W, Zhong G, Fu S, Xie H, Chi T, Li L, Rao X, Zeng S, Xu D, Wang H, et al. Microglia-based phenotypic screening identifies a novel inhibitor of neuroinflammation effective in Alzheimer’s disease models. ACS Chem Neurosci. 2016;7(11):1499–1507.
   PubMed Web of Science ®Google Scholar
• Phoebe FL, John NP, Ahmed OE, et al. Design, synthesis and evaluation of novel phthalimide derivatives as in vitro anti-microbial, anti-oxidant and anti-inflammatory agents. Molecules. 2015;20:16620–16642.
   PubMed Web of Science ®Google Scholar
• Khaled R, Phoebe FL, Hany AO. 3-Methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents. J Enz Inh Med Chem. 2016;31:318–324.
   PubMed Web of Science ®Google Scholar
• Phoebe FL, Waleed AM, Vaclav B, et al. Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: synthesis, biological activities in vitro and docking study. Eur J Med Chem. 2016;123:803–813.
   PubMed Web of Science ®Google Scholar
• Phoebe FL, John NP, Amany AA, et al. Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study. J Enz Inh Med Chem. 2017;32:805–820.
   PubMed Web of Science ®Google Scholar
• Catalina A, Isabel V. Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res. 2005;49:405–430.
   PubMed Web of Science ®Google Scholar
• Singh YP, Tej GNVC, Pandey A, Priya K, Pandey P, Shankar G, Nayak PK, Rai G, Chittiboyina AG, Doerksen RJ, et al. Design, synthesis and biological evaluation of novel naturally-inspired multifunctional molecules for the management of Alzheimer’s disease. Eur J Med Chem. 2020;198:112257–112282.
   PubMed Web of Science ®Google Scholar
• Estrada M, Herrera-Arozamena C, Pérez C, Viña D, Romero A, Morales-García JA, Pérez-Castillo A, Rodríguez-Franco MI. New cinnamic - N-benzylpiperidine and cinnamic - N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties. Eur J Med Chem. 2016;121:376–386.
   PubMed Web of Science ®Google Scholar
• Mphahlele MJ, Agbo EN, Gildenhuys S, Setshedi IB. Exploring biological activity of 4-oxo-4H-furo[2,3-h]chromene derivatives as potential multi-target-directed ligands inhibiting cholinesterases, β-secretase, cyclooxygenase-2, and lipoxygenase-5/15. Biomolecules. 2019;9(11):736–760.
   PubMed Web of Science ®Google Scholar
• Zhao XJ, Gong DM, Jiang YR, Guo D, Zhu Y, Deng YC. Multipotent AChE and BACE-1 inhibitors for the treatment of Alzheimer’s disease: design, synthesis and bio-analysis of 7-amino-1,4-dihydro-2H-isoquilin-3-one derivates. Eur J Med Chem. 2017;138:738–747.
   PubMed Web of Science ®Google Scholar
• Sun ZQ, Tu LX, Zhuo FJ, Liu SX. Design and discovery of Novel Thiazole acetamide derivatives as anticholinesterase agent for possible role in the management of Alzheimer’s. Bioorg Med Chem Lett. 2016;26(3):747–750.
   PubMed Web of Science ®Google Scholar
• Schott Y, Decker M, Rommelspacher H, Lehmann J. 6-Hydroxy- and 6-methoxybeta-carbolines as acetyl- and butyrylcholinesterase inhibitors. Bioorg Med Chem Lett. 2006;16(22):5840–5843.
   PubMed Web of Science ®Google Scholar
• Gruss M, Appenroth D, Flubacher A, Enzensperger C, Bock J, Fleck C, Gille G, Braun K. 9-Methyl-beta-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation. J Neurochem. 2012;121(6):924–931.
   PubMed Web of Science ®Google Scholar
• Hamann J, Wernicke C, Lehmann J, Reichmann H, Rommelspacher H, Gille G. 9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture. Neurochem Int. 2008;52(4–5):688–700.
   PubMed Web of Science ®Google Scholar
• Horton W, Sood A, Peerannawar S, Kugyela N, Kulkarni A, Tulsan R, Tran CD, Soule J, LeVine H, Török B, et al. Synthesis and application of betacarbolines as novel multi-functional anti-Alzheimer’s disease agents. Bioorg Med Chem Lett. 2017;27(2):232–236.
   PubMed Web of Science ®Google Scholar
• Desmarais JE, Gauthier S. Alzheimer disease: clinical use of cholinergic drugs in Alzheimer disease. Nat Rev Neurol. 2010;6(8):418–420.
   PubMed Web of Science ®Google Scholar
• Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B. Guidelines for managing Alzheimer’s disease: part II. Am Fam Physician. 2002;65(12):2525–2534.
   PubMed Web of Science ®Google Scholar
• Wang H, Zhang H. Reconsideration of anticholinesterase therapeutic strategies against Alzheimer’s disease. ACS Chem Neurosci. 2019;10(2):852–862.
   PubMed Web of Science ®Google Scholar
• Rabbani G. A concise introduction of Perkin reaction. Organic Chem Curr Res. 2018;07(02):191–195.
   Google Scholar
• El-Sawy ER, Abo-Salem HM, Mandour AH. 1H-Indole-3-carboxaldehyde: synthesis and reactions. Egypt J Chem. 2017;0 (0):0–0.
   Google Scholar
• Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7(2):88–95.
   PubMed Web of Science ®Google Scholar
• Giacobini E. Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res. 2004;50(4):433–440.
   PubMed Web of Science ®Google Scholar
• Kabir MT, Uddin MS, Begum MM, Thangapandiyan S, Rahman MS, Aleya L, Mathew B, Ahmed M, Barreto GE, Ashraf GM, et al. Cholinesterase inhibitors for Alzheimer’s disease: multitargeting strategy based on anti-Alzheimer’s drugs repositioning. Curr Pharm Des. 2019;25(33):3519–3535.
   PubMed Web of Science ®Google Scholar
• Honjo K, Black SE, Verhoeff NPLG. Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade. Can J Neurol Sci. 2012;39(6):712–728.
   PubMed Web of Science ®Google Scholar
• Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Doré V, Fowler C, Li QX, Martins R, Rowe C, et al. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature. 2018;554(7691):249–254.
   PubMed Web of Science ®Google Scholar
• Dorheim MA, Tracey WR, Pollock JS, Grammas P. Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer’s disease. Biochem Biophys Res Commun. 1994;205(1):659–665.
   PubMed Web of Science ®Google Scholar
• Aisen PS. Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer’s disease. J Pain Symptom Manage. 2002;23(4):S35–S40.
   PubMed Web of Science ®Google Scholar
• Sciacca FL, Ferri C, Licastro F, Veglia F, Biunno I, Gavazzi A, Calabrese E, Martinelli Boneschi F, Sorbi S, Mariani C, et al. Interleukin-1B polymorphism is associated with age at onset of Alzheimer’s disease. Neurobiol Aging. 2003;24(7):927–931.
   PubMed Web of Science ®Google Scholar
• Zha GF, Zhang CP, Qin HL, Jantan I, Sher M, Amjad MW, Hussain MA, Hussain Z, Bukhari SNA. Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Bioorg Med Chem. 2016;24(10):2352–2359.
   PubMed Web of Science ®Google Scholar
• Kundaikar HS, Degani MS. Insights into the interaction mechanism of ligands with Aβ42 based on molecular dynamics simulations and mechanics: implications of role of common binding site in drug design for Alzheimer’s disease. Chem Biol Drug Des. 2015;86(4):805–812.
   PubMed Web of Science ®Google Scholar
• Tateishi H, Mizoguchi Y, Kawaguchi A, Imamura Y, Matsushima J, Kunitake H, Murakawa T, Haraguchi Y, Kunitake Y, Maekawa T, et al. Changes in interleukin-1 beta induced by rTMS are significantly correlated with partial improvement of cognitive dysfunction in treatment-resistant depression: a pilot study. Psychiatry Res. 2020;289:112995.
   PubMed Web of Science ®Google Scholar
• Abdel-Fattah MM, Salama AAA, Shehata BA, Ismaiel IE. The potential effect of the angiotensin II receptor blocker telmisartan in regulating OVA-induced airway remodeling in experimental rats. Pharmacol Rep. 2015;67(5):943–951.
   PubMed Web of Science ®Google Scholar
• Stansley B, Post J, Hensley K. A comparative review of cell culture systems for the study of microglial biology in Alzheimer’s disease. J Neuroinflammation. 2012;9(1):115–118.
   PubMedGoogle Scholar
• https://www.molinspiration.com/.
   Google Scholar
• https://preadmet.bmdrc.kr/.
   Google Scholar
• http://www.swissadme.ch/index.php#.
   Google Scholar