Author(s):
Saira Asghar, Nousheen Mushtaq, Ahsaan Ahmad, Rabya Munawwar, Sumaira Ansari, Syeda Abiha Rizvi
Email(s):
saira.Asghar@hamdard.edu.pk
DOI:
10.52711/0974-360X.2023.00597 
Address:
Saira Asghar1,2, Nousheen Mushtaq1, Ahsaan Ahmad3, Rabya Munawwar4, Sumaira Ansari1, Syeda Abiha Rizvi5l
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Pakistan.
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan.
3Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi, Pakistan.
4Dow College of Pharmacy, Dow University of Health Science, Karachi, Pakistan.
5Jinnah College of Pharmacy, Sohail University, Karachi, Pakistan.
*Corresponding Author
Published In:
Volume - 16,
Issue - 8,
Year - 2023
ABSTRACT:
Oxidative stress is one of the main causative factors for pathogenesis of numerous disorders including psychological and neurodegenerative diseases (Alzheimer’s disease and Parkinsonism). Amyloid aggregates induced oxidative stress is involved in disfunction and degeneration of brain cells in Alzheimer’s disease. Antioxidants are important natural or synthetic molecules having tendency to curb free radicals and discontinuing their chain reactions prior to the damage of essential biomolecules. Drugs possessing antioxidant activity are being extensively anticipated for developing novel therapeutic agents in numerous pathological conditions accompanying oxidative stress like AD. In this study twelve tryptamine derivatives were synthesized and investigated for antioxidant, fibril inhibition and disaggregation potential. In vitro antioxidant potential of the derivatives was examined by using DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and revealed that SR10, SR14, SR23 and SR42 displayed better antioxidant activity (IC50 in the range of 0.75±0.05µM-14.43±0.77µM) than the standard ascorbic acid (IC50 =15.83±0.88µM). In vitro amyloid fibril inhibition and disaggregation assay was carried out by using HEWL (Hen egg white lysozyme) presenting moderate to high inhibition/disaggregation activities. Molecular dockingassessment recognized themode of bindingswithin active site of human antioxidant enzyme peroxiredoxin (PDB ID: 3MNG). These tryptamine derivatives with potential antioxidant and inhibition/disaggregation activitieswill be beneficialto develop and designdrug molecules forneurodegenerative disorders.
Cite this article:
Saira Asghar, Nousheen Mushtaq, Ahsaan Ahmad, Rabya Munawwar, Sumaira Ansari, Syeda Abiha Rizvi. Design, Synthesis and Therapeutic investigation of Tryptamine derivatives as Potential Antioxidant and Amyloid inhibitor/disaggregator. Research Journal of Pharmacy and Technology 2023; 16(8):3622-2. doi: 10.52711/0974-360X.2023.00597
Cite(Electronic):
Saira Asghar, Nousheen Mushtaq, Ahsaan Ahmad, Rabya Munawwar, Sumaira Ansari, Syeda Abiha Rizvi. Design, Synthesis and Therapeutic investigation of Tryptamine derivatives as Potential Antioxidant and Amyloid inhibitor/disaggregator. Research Journal of Pharmacy and Technology 2023; 16(8):3622-2. doi: 10.52711/0974-360X.2023.00597 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-8-17
REFERENCES:
1. Mónica SE. Luísa C. Daniela R. Diana C. Marisa F. Ana G. et al. Antioxidant activity of unexplored indole derivatives: Synthesisand screening.European journal of medicinal chemistry. 2010; 45(11): 4869-4878.https://doi.org/10.1016/j.ejmech.2010.07.059.
2. Afshin F. Farshid H. Ahmad MA. Lotfalah S. and Mehrdad M. Synthesis and evaluation of antioxidant activity of some novelhydroxypyridinone derivatives: a DFT approach for explanation of their radical scavenging activity.Research in Pharmaceutical Sciences. 2020; 15(6): 515. https://doi.org/10.4103/1735-5362.301336.
3. Cigdem YG. Nilay AK. Aysegul P. Belkis B. and Mustafa S. New p-substituted salicylaldehyde phenylhydrazone derivatives: synthesis, characterization, and antioxidant activities. Scientia pharmaceutica. 2014; 82(4): 735-748.https://doi.org/10.3797/scipharm.1405-04.
4. Rok M. Igor K. Alain W. and Marjana N. Development of models for prediction of the antioxidant activity of derivatives of natural compounds. Analytica chimica acta. 2015; 868: 23-35.https://doi.org/10.1016/j.aca.2015.01.050.
5. Francik R. Kazek G. Cegła M. and Stępniewski M. Antioxidant activity of β-carboline derivatives. Acta Poloniae Pharmaceutica. Drug Research. 2011; 68(2).https://www.ptfarm.pl/wydawnictwa/czasopisma/acta-poloniae-pharmaceutica/110/-/13464.
6. GabrS.Bakr R.Mostafa E , El-Fishawy A. andEl-Alfy T. Antioxidant activity and molecular docking study of Erythrina× neillii polyphenolics. South African Journal of Botany. 2019; 121: 470-477.https://doi.org/10.1016/j.sajb.2018.12.011.
7. Nilima K. Dilshad NL. Biplab KD. Uttom K. and Abu SS. Synthesis and antioxidant activity of some novel benzimidazole derivatives. Dhaka University Journal of Pharmaceutical Sciences. 2017; 16(2): 245-249. https://doi.org/10.3329/dujps.v16i2.35263.
8. Qazi Y. and Zahid Z. 4-Aminoantipyrine Analogs as Anti-inflammatory and Antioxidant agents: Synthesis, Biological Evaluation and Molecular Docking Studies. International Journal of Pharmaceutical Investigation. 2021; 11(1): 14-22.https://doi.org/10.5530/ijpi.2021.1.4.
9. SüzenS.Antioxidant activities of synthetic indole derivatives and possible activity mechanisms, in Bioactive Heterocycles V. 2007; Springer. 145-178. https://doi.org/10.1007/7081_200.
10. Thanchanok P. Shinya K. Sarin T. Jutamas J. Jaturong P. Worawan K. et al.Semisynthesis and biological evaluation of prenylated resveratrol derivatives as multi-targeted agents for Alzheimer’s disease. Journal of natural medicines. 2017; 71(4): 665-682. https://doi.org/10.1007/s11418-017-1097-2.
11. Hasti S. Gandavaram P. Chintha V. Chamarthi NR. and Wudayagiri R.In silico and in vitro antioxidant activity profiles of urea and thiourea derivatives of 5-hydroxytryptophan. Journal of Receptors and Signal Transduction. 2019; 39(4): 373-381. https://doi.org/10.1080/10799893.2019.1683864.
12. Brad F. and Sajay G. A review of antioxidants and Alzheimer’s disease. Annals of Clinical Psychiatry. 2005; 17(4): 269-286. https://doi.org/10.3109/10401230500296428.
13. FengY. andWang X. Antioxidant therapies for Alzheimer's disease. Oxidative medicine and cellular longevity. 2012; https://doi.org/10.1155/2012/472932.
14. Pen LT. and Ming KH. Free radical scavenging and antioxidative activity of melatonin derivatives. Journal of pharmacy and pharmacology. 2003; 55(12): 1655-1660.https://doi.org/10.1211/0022357022250.
15. KousaraS.Anjuma SN. Jaleela F. Khana J. and Naseema S. Biomedical significance of tryptamine: A review. J. Pharmacovigil. 2017; 5(5). https://doi.org/10.4172/2329-6887.1000239.
16. Beata J. Weronika K. Michał P. Beata W. Urszula R. Tomasz P. et al.Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives. Scientific Reports. 2021; 1(1): 1-14.https://doi.org/10.1038/s41598-021-94904-z.
17. Bijo M. Della GT. Githa EM. Sahab U. Sini TI. Hoon K.et al.Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie. 2019; 352(11): 1900177. https://doi.org/10.1002/ardp.201900177.
18. Atul JR. Yogesh TN. and Jayesh SB. Synthesis and Antioxidant Activity of Functionalized Pyridinyl-Methylthiosemicarbazide Derivatives. Polycyclic Aromatic Compounds. 2020; 1-10. https://doi.org/10.1080/10406638.2020.1866033.
19. Zhen Z. Ying LG.Zheng YW. Huan NW. Yan Z. Xue MC.et al.Synthesis and biological evaluation of novel indoleamide derivatives as antioxidative and antitumor agents. Journal of Heterocyclic Chemistry. 2020; 57(3): 1165-1172. https://doi.org/10.1002/jhet.3853.
20. RamshiniH.Saeidian S. andNazemian L. Synthesis and Identification of Novel Aromatic Compound as Inhibitor of Lysozyme Amyloid Aggregation. Journal of Sabzevar University of Medical Sciences. 2020; 27(1): 55-63.
21. Hossein A. Elaheh HZ. Mahmood T. Nabeela M. Gopal NS. and Rizwan HK.Discovery of a tetracyclic indole alkaloid that postpones fibrillation of hen egg white lysozyme protein. International Journal of Biological Macromolecules. 2021; 183: 1939-1947. https://doi.org/10.1016/j.ijbiomac.2021.05.212.
22. Rabya M. Nousheen M. Ahsaan A. Syed SMG. Saman U.and Shamim A. et al.Molecular docking, synthesis and biological evaluation of phenacyl derivatives of 9-aminoacridine as anti-Alzheimer's agent. Pakistan journal of pharmaceutical sciences. 2020; 33(2). doi.org/10.36721/PJPS.2020.33.2.REG.659-668.1.
23. Wario G. Milkyas E. Emebet G. Rajalakshmanan E. Temesgen A. and Yadessa M. Antibacterial and antioxidant activities of extracts and isolated compounds from the roots extract of Cucumis prophetarum and in silico study on DNA gyrase and human peroxiredoxin 5. BMC chemistry. 2021; 15(1): 1-17. https://doi.org/10.1186/s13065-021-00791-w.
24. Aftab A.Talha J. and Parvej A.In vitro antioxidant and anti-inflammatory activities of green cardamom essential oil and in silico molecular docking of its major bioactives. Journal of Taibah University for Science. 2021; 15(1): 757-768. https://doi.org/10.1080/16583655.2021.2002550.
25. BharathiR. and Santhi N. 4-(3-(2-amino-3, 5-dibromophenyl)-1-(4-substitutedbenzoyl)-4, 5-dihydro-1H-pyrazol-5-yl) benzonitrile as a novel anti-Inflammatory scaffold: Synthesis, biological evaluation and docking studies. World Scientific News. 2019; 126: 148-162.https://doi.org/10.6026%2F97320630016929.
26. Amjad K.Nidal J. Muhammad H. and Linda I. In vitro biological evaluation of benzodioxol derivatives as antimicrobial and antioxidant agents. Arabian Journal for Science and Engineering. 2021; 46(6): 5447-5453. https://doi.org/10.1007/s13369-021-05332-0.
27. Rawaida AH.and Mai MO. New benzoic acid derivatives from Cassia italica growing in Saudi Arabia and their antioxidant activity. Saudi Pharmaceutical Journal. 2020; 28(9): 1112-1117. https://doi.org/10.1016/j.jsps.2020.07.012.
28. Haydi SE. Mostafa ME. Shaymaa EK. Hoda D. Waleed AM. Soad AHM.Design, synthesis, biological evaluation and docking studies of new 3-(4, 5-dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole derivatives as potent antioxidants and 15-lipoxygenase inhibitors. European journal of medicinal chemistry. 2018; 145: 594-605. https://doi.org/10.1016/j.ejmech.2018.01.026.
29. Mohammad F. Mohammad KS. Syed MZ. Faez IK. Imtaiyaz H. Rizwan HK.An In Vitro elucidation of the antiaggregatory potential of Diosminover thermally induced unfolding of hen egg white lysozyme; A preventive quest for lysozyme amyloidosis. International journal of biological macromolecules. 2019; 129: 1015-1023. https://doi.org/10.1016/j.ijbiomac.2019.02.107.
30. Fakhrossadat M.Afshin M. Marzieh M. and Leila H. Inhibition of amyloid fibrillation of hen egg-white lysozyme by the natural and synthetic curcuminoids. RSC advances. 2016; 6(28): 23148-23160. https://doi.org/10.1039/C5RA18992F.
31. Chun W. Justin S. and Joan ES.Binding of Congo red to amyloid protofibrils of the Alzheimer Aβ9–40 peptide probed by molecular dynamics simulations. Biophysical journal. 2012; 103(3): 550-557. https://doi.org/10.1016/j.bpj.2012.07.008.
32. Chu W. Zhixiang W. Hongxing L. Wei Z. and Yong D. Dual binding modes of Congo red to amyloid protofibril surface observed in molecular dynamics simulations. Journal of the American Chemical Society. 2007;129(5): 1225-1232. https://doi.org/10.1021/ja0662772.