Main Article Content
The sustained interest in the design of potent antioxidants drugs over the years can be attributed to the indispensable roles antioxidants play in the mitigation of oxidative stress and its concomitant diseases. The high demand for exogenous antioxidants has been ascribed to the prevalence of oxidative stress-mediated diseases such as cancer, diabetes, stroke, cell aging, arteriosclerosis and central nervous system disorders occasioned by a biochemical disequilibrium between the production of free radicals and the body’s ability to eliminate these reactive species from the biological system. COVID-19 severity and death have been linked to a free radical generating process known as the cytokine storm. In an attempt to maintain optimal body function, antioxidant supplementation has increasingly become a wide spread practice because of antioxidants’ ability to directly scavenge free radicals, inhibit oxidative chain reactions thereby increasing the antioxidant defenses of the body. Recent data showed that researchers had made significant efforts to demonstrate the importance and timeliness of antioxidant therapy based on drug design from natural and synthetic sources. Therefore this review presents antioxidant drug design methodologies, identifying the lead and hits to provide a historical and up-to-date collection of research briefs on antioxidant drug design into a single piece in order to ensure easy accessibility, motivate readership and inspire future researches.
German JB. Food processing and lipid oxidation impact of processing on food safety. Adv. Expt. Med. Biol. 1999;459:23-50.
American chemical society national historic chemical landmarks Moses Gomberg and organic free radicals 2000. Available:http://www.acs.org/content/acs/en/education/whatischemistry
Moureu C, Dufraisse C. Surl antoxydation: Les androgens. Comptes Rendus des scances et memories de la societe de Biologie (in French). 1922;86:321-322.
Villines Z. Antioxidants and free radicals; 2017. Available:wwww.medicalnewstoday.com
Bacchetti T, Morresi C, Bellachioma L, Ferretti G. Antioxidant and pro-oxidant properties of Carthamus tinctorius, Hydroxy safflor Yellow A, and Safflor Yellow A. Antioxidant. 2020; 9(2):119.
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/ nitrosative stress: Current state. Nutr. J. 2016;15:71.
Augustyniak A, strzydlewska E, Zdolnosci antyoksydacyjne w starzejacym sie organizmie [antioxidative abilities during aging]. Postepy Hig Med Dosw (online). 2004;58:194-201.
Durarte TL, Lunec J. Review part series: From dietary antioxidants to regulators in cellular signalling and gene expression review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamine C. Free Radic. Res. 2005;39(7):671-686.
Galecka E, Mrowicka M, Malinowska J, Galecki P. Chosen non-enzymatic substances that participate in a protection against overproduction of free radicals. Polski Merkuriusz Lekarski Organ Polskiego Towarzystwa Lekarskiego. 2008;25(147):269-272.
Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllen HC. Impact of antioxidant supplementation on chemotherapeutic efficacy a systematic review of the evidence from randomized control trials. Cancer Treat. Rev 2007; 339(5):407-418.
Halliwell B. Establishing the significance and optimal intake of dietary antioxidants: The biomarker concept. Nutr. Rev 1999; 57:104-113.
Gilgun-sherki Y, Resenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury current state. Pharmalcol. Rev. 2002;54: 271-84.
Altun I, kurutas EB. Protein-coupled estrogenic receptor levels after peripheral nerve injury in an experimental rat model. World Neurosurg. 2015;84:1903-6.
Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003;361:2017-23.
Aruoma OI. Free radicals, oxidative stress and antioxidants in human health and disease. J. Am Oil chem. Soc 1998; 75:199-212.
Hertog, MGL, Feskens EJM, Kromhout D, Hollman PCH, Katan MB. Dietary antioxidant flavonoids and risk of coronary heart disease. The Zutphen elderly study. Lancet. 1993;342:1007-1011.
Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic toxicity: A systematic review of the evidence from randomized controlled trials. Int. J. Cancer. 2008; 123(6):1227-1239.
Kadosh E, Snir-Alkalay I, Venkatachalam A, May S, Lasry A, Elyada E, et al. The gut microbiome switches mutant P53 from tumour-suppressive to oncogenic. Nature 2020;586:133-138.
U.S Department of Agriculture, Research Service. Oxygen radical absorbance capacity (ORAC) of selected foods, release 2. Nutrient Data Laboratory Home page; 2010. Available:http://www.ars.usda.gov/nutrientdata/orac.
Aruoma CI, Akanmu D, Cecchini R, Halliwell B. Evaluation of the ability of the angiotensin-coverting enzyme inhibitor captopril to scavenge reactive oxygen species. Chem. Biol. Interact. 1991;77: 363-314.
Bagchi D, Iyengar J, stockwell P, Das DK. Enhanced prostaglandin production in the ischemic reperfused myocardium by captopril linked with its free radical scavenging action. Prostaglandins Leukot. Essent. 1989;38:145-150.
Fisher J, Ganellin CR. Analogue based drug discovery. 1st edn. Germany: Wiley/VCH verlag GmbH, Weinheim; 2006.
Lee D, Park Y, Song M, Kim DR, Zada S, Kim D. Cytoprotective effects of Delphinidin for human chondrocytes against oxidative stress through activation of autophagy. Antioxidant. 2020;9(1):83.
Kursvietiene L, Mongirdiene A, Bernatoniene J, Sulinskiene J, Staneviciene I. Selenium anticancer properties and impact on cellular redox status. Antioxidant. 2020:9(1):80.
Jakubczyk K, Dec K, Kaldunska J. Kawczuga D, Kochman J, Janda K. Reactive oxygen species-sources, functions, oxidative damage. Pol Merkur Lekarski. 2020;48(284):124-127.
Keller JN, Kindy MS, Holtsberg FW. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: Suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci. 1998;18687-697.
Sano M, Ernesto C, Thomas RG, et al. Members of the Alzheimers disease cooperative study, A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med. 1997;3361216-1222.
Peyser CE, Folstein M, Chase GA, et al. Trial of D-α-tocopherol in Huntington’s disease. Am J Psychiatry.1995;152:1771-1775.
Ogunmekam AO, Hwang PA. A randomized, double–blind, placebo-controlled, clinical trial of D-α-tocopherol acetate (Vitamin E), as add-on therapy, for epilepsy in children. Epilepsia. 1989;3084-89.
Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, et al. Vitamin E and C in the prevention of cardiovascular disease in men: the physician health study II randomised controlled trial. JAMA. 2008; 300:2121-2133.
Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J. et al. Vitamin E and C in the prevention of prostrate and total cancer in men: the physicians health study II randomized controlled trial. JAMA. 2009;301:52-62.
Kavanagh RJ, Kam PCA. Lazaroids: Efficacy and mechanism of action of the 21-aminosteroids in neuroprotection. Br.J. Anaesth. 2001;86:110-19.
The RANTTAS investigators, a randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS). Stroke. 1996;271453-1438.
Kassel NF, Haley EC,Jr, Apperosn-Hansen C, Alves WM. Randomized, double –blind, vehicle controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid haemorrhage; a cooperative study in Europe, Australia, and New Zealand. J Neurosurg. 1996;84:221-228.
Brecken MB, Shepard MJ, Holford TR et al. National acute spinal cord injury study, administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: Results of the third national acute spinal cord injury randimized controlled trial. JAMA. 1997;277:1597-1604.
Cahill L, Hall ED. Is it time to resurrect ‘lazaroids”? J. Neurosci Res. 2017;95(1-2):17-20.
Pathania S, Rawal RK. Pyrrolopyrimidines: An update on recent advancements in their medicinal attributes. Eur J Med Chem. 2018;157:503-526.
Hall ED, Andrus PK, Smith SL, et al. Pyrrolopyrimidines; novel brain penetrating antioxidants with neuroprotective activity in brain injury and ischemia models. J. Pharmacol. Exp. Ther. 1997;281895-904.
Louwerse ES, Weverling GJ, Bossuyt PMM, Posthumus Meyjesss FE, DeJong JMB. Randomized, double–blind, controlled trial of acetyleysteine in amyotrophic lateral sclerosis. Arch Neurol. 1995;52:559-564.
Noguchi N. Ebselen, a useful tool for understanding cellular redox biology and a promising drug candidate for use in human diseases. Arch Biochem Biophys. 2016; 595:109-112.
Azad GK, Tomer RS. Ebselen, a promising antioxidant drug; mechanisms of action and targets of biological pathways. Mol Biol Rep. 2014;41(8):4865-4879.
Yamaguchi T, Sano K, Takakura K, et al. Ebselen study group, Ebselen in acute ischemic stroke a placebo-controlled, double –blind clinical trial. Stroke. 1998; 2912-17.
Arenas E. Method to combat Parkinson’s disease by astrocyte to neuron conversion. Nature. 2020;582:489-490.
Olanow CW, Hauser RA, Gauger L, et al. the effect of deprenyl and levodopa on the progression of parkinson’s disease. Ann Neurol. 1995;38;771-777.
Palhagen S, Heinonen EH, Hagglund J, et al. Swedish Parkinson study group, selegiline delays the onset of disability in de novo parkinsonian patients. Neurology 1998;51:420-525.
Tabi T, Vecsei L, Youdim MB, et al. Selegiline: A molecule with innovative potential. J Neural Transm. 2020;127:381-842.
Carlsson MS, Denneberg T, Emanuelsson B et al. Steady state pharmacokinetic of 2-mercaptopropionylglycine (Tiopronin) in healthy volunteers and patients with cystinuria. Drug Invest. 1994;7:41-51.
Modersitzki F, Goldfarb DS, Goldstein RL, et al. Assessment of health- related quality of life in patients with cystinuria on tiopronin therapy. Urolitiasis. 2020;48:313-320.
Pacher P, Nivorozhkin A, Szabo C. Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol. Pharmacol. Rev. 2006;58(1):87-114.
AHFS Drug information. McEvoy GK ed. Allopurinol. American society of Health-System Pharmacists. 2003;35:46-50.
Uchide N, Toyoda H. Antioxidant therapy as a potential approach to severe influenza –associated complications. Molecules 2011;16(3):2032-2052.
Madsen U, Krogsgaard-Larsen P, Liljefors T. Textbook of drug design and discovery. Washington, D.C Taylor and Francis; 2002.
Ganellin CR, Jefferis R, Roberts SM. Introduction to biological and small molecule drug research and development: theory and case studies,1st edn. USA: Elsevier; 2013.
Ghasemi P, Mehri F. The role of different sampling methods in improving biological activity prediction using deep belief network. J. Comput. Chem. 2016;38(10): 1-8.
Reynolds CH, Merz KM, Ringe D. Drug design: Structure and ligand-based approaches,1st edn. Cambridge, UK: Cambridge Univeristy Press; 2006.
Harren J, Leach AR (Eds). Structure–based drug discovery. Berlin: springer; 2007.
Klebe G. Recent developments in structure-based drug design. J. Mol Med. 2000;78(5):269-81.
De Azevedo WF, Dias R. Computational methods for calculation of ligand binding affinity. Curr. Drug Targets. 2008;9(12): 1031-9.
Singh J, Chuaqui CE, Boriack-Sjodin PA, Lee WC, Pontz T, Corbley MJ, Cheung HK, et al. Successful shape-based virtual screening: the discovery of potent inhibitor of the type I TGF-beta receptor kinase (TbetaRI). Bioorg. Org. Med. Chem. Lett 2003;13(24):4355-9.
Waring MJ, Arrowsmith J, Leach AR, Leeson PD, Mandrell S, Owen RM, et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat. Rev. Drug Discov. 2015; 14(7):475-86.
Baunthiyal M, singh V, Dwivedi S. Insights of antioxidants as molecules for drug discovery. Int J. Pharmacol 2017;13(7): 874-889.
Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005;78(5): 431-441.
Drahl C, cravat BF, Sorensen EJ. Protein–reactive natural products. Angewandte Chemie Int. Edn. 2005;44:5788-5809.
Roy K, Kar S, Das RN. Chapter 1.2: What is QSAR? Definitions and formulism A primer on QSAR/QSPR modelling: Fundamental concepts. New York: Springer-verlag Inc. 2015;2-6.
Ghasemi P, Mehri P. Neural network and deep–learning algorithms used in QSAR studies: merits and draw backs. Drug Discov. Today. 2018;23(10):1784-1790.
Natasenamat C, Isarankura Na- Ayudhya C, Naenna T, Prachayasi ttikul V. A practical overview of quantitative structure activity relationship. Excli J. 2009;8:74-88.
Todeschini R, consonni V. Handbook of molecular descriptors. New York: Wiley –VCH; Weinheinnm; 2000.
Hansch C, Gao H. Comparative QSAR: Radical reactions of benzene derivatives in chemistry and biology. Chem. Rev. 1997; 97(8):2995-3060.
Dilabio GA, Pratt DA, Wright JS. Theoretical calculation of ionization potentials for disubstituted benzenes; additivity Vs non- additivity of substituent effects. J. Org. Chem. 2000;65(7):2195-2203.
Vajragupta O, Boonchoong P, Wongkrajang Y. Comparative quantitative structure activity study of radical scavengers. Bioorg. Med. Chem. 2000; 8(11):2617-2628.
Zhang H. Structure activity relationships and rational design strategies for radical scavenging antioxidant. Curr comput Aided Drug Des. 2005;1:257-273.
Ahmad MM, Alwi SR, Jamaludin R, Chua LS, Mustaffa AA. Quantitative activity relationship model for antioxidant activity of flavonoid compounds in traditional Chinese Herbs. Chemical Engr. Transactions. 2017; 56:1039-1044.
Haenen GRMM, Arts MJTJ, Bast A, coleman MD. Structure ad activity in assessing antioxidant activity In vitro and In vivo; a critical appraisal illustrated with the flavonoids. Toxicol. Phar. 2006;21: 191.
McPhail DB, Hartley RC, Gardner PT, Duthie GG. Kinetic and stoichiometric assessment of the antioxidant activity of flavonoids. J. Agric Food Chem. 2003;51: 1684-1690.
Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidants determination of radical-scavenging efficiencies. Methods Enzymol. 1990;186:343-355.
Sroka ZZ, Antioxidative and antiradical properties of plant phenolics. Z Naturforsch CJ Biosci. 2005;60(11-12):833-843.
Arora, A Nair MG Strasburg GM Antioxidant activity of isoflavones and their biological metabolites in a liposomal system. Arch. Biochem Biophys. 1998; 356(2):133-141.
Burkovic V, klasinc L, Bors, WJ. Kinetic study of flavonoid reactions with stable radicals. J Agric Food Chem. 2004;52(10): 2816-2820.
Van Acker SA Van den Berg DJ, Tromp MN et al. Structural aspects of antioxidant activity of flavonoids. Free radic Biol Med. 1996;20(3):331-342.
Cotelle N, Bernier JL, Catteau JP, Pommery J, Wallet JC, Gadou EM. Antioxidant properties of hydroxyl flavones. Free Radic Biol Med. 1996;20(1):35-43.
Pieta P. Flavonoids as antioxidants. J. Nat. Prod. 2000;63(7):1035-1042
Foti M, Piattelli M, Baratta MT, Ruberto G. Flavonoids, coumarins, and cinnamic acids as antioxidants in a micellar system. Structure activity relationship. J. Agric. Food Chem. 1996;44(2):497-501.
Dugas. Jr AJ, Castaneda–Acosta J, Bonin GC, Price KL, Fischer NH, Winston GW. Evaluation of the total peroxyl radical-scavenging capacity of flavonoids structure-activity relationship. J. Nat. Prod. 2000;63(3):327-331.
Guo Q, zhao BL, Shen SR, Hou JW, Hu JG, Xin WJ, et al. ESR study on the structure-antioxidant activity relationship of tea catechins and their epimes. Biochimica et biophysica Acta. 1999;1427(1):13-23.
Costantino L, Rastelli G, Albasini A, Anthocyanidines as inhibitors of xanthine oxide. Pharmazie. 1995;50:573-574.
Baj A, Cedrowski J, Olchowik-Grabarek E, Ratkiwicz A, witkowski S. Synthesis DFT calculations, and In vitro antioxidant study on novel carba-analogs of vitamin E. Antioxidant. 2019;8(12):589.
Burton, GW, Doba T, Gabe EJ, Hughes L, Lee FL, Prasad L, Ingold KU. Autoxidation of biological molecules for maximizing the antioxidant activity of phenols. J. Am. Chem. Soc 1985;107(24):7053-7065.
Mukai K, Tokunaga A, Itoh S, Kanesaki Y, Ohara K, Nagaoka S, Abe K. Structure activity relationship of the free radical-scavenging reaction by vitamin E (α,ß,ϒ,δ-tocopherols) and ubiquinol-10: pH dependence of the reaction rates. J. phys. Chem. B. 2007;111(3):652-662.
Druand A, Farce A, Carato P, Dilly S, Yous S, Berthelot P, et al. Quantitative structure activity relationships studies of antioxidant hexahydropyridoindoles and flavonoid derivatives. J. Enzyme Inhib Med Chem. 2007;22(5):556-562.
Filipovic M, Markovic Z, Dorovic J, Markovic JD, Lucic B, Amic D. QSAR of the free radical scavenging potency of selected hydroxyl-benzoic acids and simple phenolics. Comptes Rendus Chimie. 2015;18(5):492-498.
Hoelz LVB, Horta BAC, Araujo JQ, Albuquerque MG, de Alencastro RB, da Silva JFM. Quantitative structure activity relationships of antioxidant phenolic compounds. J. Chem. Pharm. Res. 2010; 2(5):291-306.
Same W, Nunthanavanit P, Ungwitayatorn J. 3-D-QSAR investigation of synthetioc chromone derivatives by molecular field analysis. Int .J. Mol. Sci. 2008;9:235-246.
Chen N, Chen J, YaO B, Li Z. QSAR study on antioxidant tripetides and the antioxidant activity of the designed tripeptides in free radical system. Molecules. 2018;23(6);1407.
Daramola B. Anthology of historical development and some research progress glimpses on phytochemical antioxidants phenomenon. Int. J. Biotechnol. Mol. Biol. Res. 2014;5(3):13-26.
Knog L, Sun ZL, Wang LF, Zhang HY, Yao SD. Theoretical elucidation of nitrogen dioxide radical-scavenging activity difference of hydrocinnamic acid derivatives. Helvetica Chemica Acta. 2004; 87: 511-515.
Liwinienko G, Ingold KU. Abnormal solvent effectson hydrogen atom abstraction. The reaction of phenols with 2,2-diphenyl-1-picrylhydrazyl(DPPH) in alcohols. J. Org. Chem. 2003;68:3433.
Wright JS, Johnson ER, Dilabio GA. Predicting the activity of phenolic antioxidants: Theoretical method, analysis of substituent effects, and application to major families of antioxidants. J. Am. Chem. Soc. 2001;123(6):1173-1183.
Frankel EN, Hang SW, Kanner J, German JB. Interfacial phenomena in the evaluation of antioxidants: Bulk oils vs emulsions. J. Agric Food Chem. 1994; 42(5):1054-1059.
Son S, Lewis BA. Free radical scavenging and antioxidative activity of caffeic acid amide and ester analogues: structure-activity relationship. J. Agric. Food Chem. 2002;50(3):468-472.
Bowry VW, Ingold KU. The unexpected role of vitamin E (α-tocopherol) in the peroxidation of human low-density lipoprotein. Acc. Chem. Res.1999;32(1): 27-34.
Dangles O, Dufour, C, Fargeix G. Inhibition of lipid peroxidation by quercetin and quercetin derivatives. J. Chem. Soc. Perkin Trans. 2000;2:1215-1222.
Nakao K, Shimizu R, Kubota H, Yasuhara M, Hashimura Y, Suzuki T, Fujita T, Ohmizu H. Quantitative structure-activity analyses of novel hydroxyphenylurea derivatives as antioxidants. Bioorg. Med. Chem. 1998;6(6):849-868.
Palozza P, Piccioni E, Avanzi L, Vertuani S & Calviello G, Manfredini S. Design, synthesis, and antioxidant activity of FeAOX-6, a novel agent deriving from a molecular combination of the chromanyl and polyisoprenyl moieties. Free radic. Biol. Med. 2002;33(12):1724-1735.
Pratt DA, DiLabio GA, Brigati G, pedulli GF, Valgimigli L. 5-pyrimidinols: Novel chain-breaking antioxidants more effective than phenols. J. Am Soc. 2001;123(19): 4625-4626.
Valgimigli L, Bragati G, Pedulli GF, DiLabio GA, Mastragostino M, Arbizzani C, Pratt DA. The effect of ring nitrogen atoms on the homolytic reactivity of phenolic compounds: Understanding the radical-scavenging ability of 5-pyrimidinols. Chem. Eur. J. 2003;9:4997-5010.
Fukuhara K, Nakanishi I, Kansui H, sugiyama E, Kimura M, Shimada T, Urano S, Yamaguchi K, Miyata N. Enhanced radical-scavenging activity of a planar catechin analogue. J. Am Chem. Soc. 2002;124:5952-3.
Fukuhara K, Nakanishi I, Shimada T, Miyazaki K, Hakamata W, Urano S, Ikota N, Ozawa T, Okuda H, Miyata N, Fukuzumi S. A planar catechin analogue as a promising antioxidant with reduced prooxidant activity. Chem Res Toxicol. 2003;16:81-6.
Karmaker N, Lira DN, Das BK, Kumar U, Rouf ASS. Synthesis and antioxidant activity of some novel benzimidazole derivatives. Dhaka Univ. J. Pharm. Sci. 2017;16(2):245-249.
Watanabe T, Tahara M, Todo S. The novel antioxidant edaravone: From bench to bedside. Cardiovasc. Therap. 2008;26(2): 101-14.
Martincic R, Mravljak J, Svajger U, Perdih A, Anderluh M, Novic M. In silico discovery of novel potent antioxidants on the basis of pulvinic acid and coumarine derivatives and their experimental evaluation. PLoS One. 2015;10(10):0140602.
Egbujor MC, Okoro UC, 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.
Egbujor MC, Okoro UC, Anieze EO, Amadi UB, Okenwa-Ani CG, Chidebelu IC. Synthesis and characterization of benzoylated sulfamoyl carboxylic acids. MOJ Bioog Org Chem. 2020;4(1):22-25.
Egbujor MC, Okoro UC. New methionine-based p-toluenesulphonamoyl carboxamide derivatives as antimicrobial and antioxidant agents: Design, synthesis. J. Pharm. Res. Int. 2019;28(1):1-12.
Egbujor, MC, Okoro UC, Okafor S, Nwankwo NE. 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.
Egbujor MC, Okoro UC, Okafor S. Novel alanine-based antimicrobial and antioxidant agents: Synthesis and molecular docking. Indian J. Sci. Technol 2020;13(09):1003-1014.
Egbujor MC, Okoro UC, Nwobodo DC, Ezeagu CU, Amadi UB, Okenwa-Ani, CG, Ugwu JI, Okoye IG, Abu IP, Egwuatu PI. Design, synthesis, antimicrobial and antioxidant activities of novel threonine-based sulfonamide derivatives. J. Pharm. Res. Int. 2020;32(8):51-61.
Egbujor MC, Okoro UC, Okafor S, Nwankwo NE. Synthesis, characterization and in silico studies of novel alkanoylated 4-methylphenyl sulphonamoyl carboxylic acids as potential antimicrobial and antioxidantagents. Inter. J. Pharm. Phytopharm. Res. 2019;9(3):89-97.
Egbujor MC, Okoro UC, Egu SA, Egwuatu PI, Amasiatu IS, Eze FU. Design, synthesis and biological evaluation of alanine-based sulphonamide derivatives. Int. J. Res. Pharm. Sci. 2020;11(4):6449-6458.
Egbujor MC, Okoro UC, Okafor SN, Amasiatu IS, Amadi UB, Egwuatu PI. Synthesis, molecular docking and pharmacological evaluation of new 4-methylphenylsulphamoyl carboxylic acids analogs. Int. J. Res. Pharm. Sci. 2020; 11(4):5357-5366.
Wang J, Huang L, Cheng C, Li G, Xie J, et al. Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanism as potential anti-ischemic stroke agents. Act a Pharmacentica Sinica B. 2019;9(2):335-350.
Ugwu DI, Ezema BE, Okoro UC, Eze FU, Ekoh OC, Egbujor MC Ugwuja DI. Synthesis and pharmacological applications of chalcones: A review. Int. J. Chem. Sci. 2015;13(1):459-500.
Barnham KJ, Masters CL, Bush AI. Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov. 2004;3(3): 205-14.
Zhang H, Yang D, Tang G. Multipotent antioxidants: From screening to design. Drug Discov. Today. 2006;11(15/16):749-754.
Antonello, A, Hrelia P, Leonardi A, Marucci G, Rosini M, Tarozzi A, Tumiatti V, Melchiorre C. Design, synthesis, and biological evaluation of prazosin-related derivatives as multipotent compounds. J. Med Chem. 2005;48(1):28-31.
Rosini M, Andrisano V, Bartolini M, Bolognesi ML, Hrelia P, Minarini A, Tarozzi A, Melchiorre C. Rational approach to discover multipotent anti-Alzheimer drugs. J. Med. Chem.2005;48(2):360-363.
Rodriguez- Franco MI, Fernandez-Bachiller MI, Perez C, Hernandez-Ledesma B, Bartolome B. Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetyl cholinesterase inhibitory and antioxidant properties. J. Med. Chem. 2006;49;459-462.
Adewusi EA, Moodley N, Steenkamp V. Antioxidant and acetylcholinesterase inhibitory activity of selected southern African medicinal plants. S. Afr. J. Bot. 2011;77(3):638-644.
Reza ASMA, Hossain MS, Akhter S, Rahman R, Nasrin S, Uddi J, Sadik G, Alam AHMK. In vitro antioxidant and cholinesterase inhibitory activity of Elatostema papillosum leaves and correlation with their phytochemical profiles: a study relevant to the treatment of Alzheimer’s disease. BMC complement Altern Med. 2018;18:123.
Doulgkeris CM, et al. Synthesis and pharmacochemical study of novel polyfunctional molecules combining anti-inflammatory, antioxidant and hypocholesterolemic properties. Bioorg. Med. Chem. Lett. 2006;16:825-829.
Yehye WA, Rahamn NA, Saad O, Ariffin A, Hamid SBA, Alhadi AA. Rational design and synthesis of new, high efficiency, multipotent Schiff base-1,2,4-triazole antioxidants bearing butylated hydroxytohene moieties. Molecule. 2016; 21(7):847.
Ladopoulou E, Matralis AN, Kourounakis AP. New multifunctional di-tert-butylphenoloctahydro (pyridolbe) derivatives with antioxidant, antihyperlipi-demic, and antidiabetic action. J. Med. Chem. 2013;56(8):3330-3338.
Matralis AN, Kourounakis AP. Optimizing the pharmacological profile of new bifunctional antihyperlipidemic/antioxidant morpholine derivatives. ACS Med. Chem. Lett. 2019;10(1):98-104.
Kato T, et al. Novel calcium antagonist with both calcium overload inhibition and antioxidant activity. 1,2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(amniopropyl thiazolidinone derivatives. J. Med. Chem 1999;42:3134-3146.
Santa-Helena E, Cabrera DC, Teixeira S, Rodrigues J, Castro M, Montes D’oca MG, et al. New fatty dihydropyridines potential in H9c2 cardioblasts to¬ simulated ischemia and reperfusion. Biomed Pharmacotherap. 2019;109:1532-1540.
Maliar T, et al. Structural aspects of flavonoids as trypsin inhibitor. Eur J. Med. Chem. 2004;39:241-248.
Saito A, sugisawa A, Umegaki K, sunagawa H. Protective effects of quercetin and its metabolites on H2O2-induced chromosomal damage to WIL2-NS cell. Biosci. Biotech. Biochem. 2004;68: 271-276.
Simanjuntak K, Simanjuntak JE, Prasasty VD. Structure-based drug design of quercetin and its derivatives against HMGBI. Biomed. Pharmacol J. 2017; 10(4).
Adahoun MA, Al-Akhras MH, Jaafar MS, Bououdina M. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles Artifical cells, Nanomedicine and Biotechnology. An internation Jorunal 2017;45(1).
Chen C, Sun W, Wang X, Wang Y, Wang P. Rational design of curcumin loaded multifunctional mesoporous silica nano-particles to anhence the cytotoxicity for targeted and controlled druy release. Material science & engineering C. 2018; 85:88-96.
Barzegar A. Antioxidant activity of polyhenolic myricetin In vitro cell-free and cell-based systems. Mol Biol Res Commun. 2016;5(2):87-95.
Ruan X, Zhang C, Jiang S, GuoT, Xia R, Chen Y, et al. Design, synthesis and biological activity of novel myricetin derivatives containg amide, thioether, and 1,3,4-Thiadiazole moieties. Molecules. 2018;23:3132.