Abstract
Objectives: 1,2-thiazine and pyridine heterocycles drew much attention due to their biological activities, including antioxidant activity. Based on fragment-based drug design, novel pyrido[1,2]thiazines 9a-c, thiazolidinopyrido[1,2], thiazines 10a-c and azetidinopyrido[1,2]thiazines 11a-c were designed and prepared.
Methods: These novel derivatives 9a-c, 10a-c and 11a-c were subjected to screening for their antioxidant activity via various assays as DPPH radical scavenging potential, reducing power assay and metal chelating potential.
Results: All the assayed derivatives exhibited excellent antioxidant potential and the tested compounds 9a, 9b, 10a, 10b, 11a and 11b exhibited higher DPPH scavenging potential (EC50 = 32.7, 53, 36.1, 60, 40.6 and 67 μM, respectively) than ascorbic acid (EC50 = 86.58 μM). While targets 9a, 10a and 11a (RP50 = 52.19, 59.16 and 52.25 μM, respectively) exhibited better reducing power than the ascorbic acid (RP50 = 84.66 μM). The computational analysis had been utilized to prophesy the bioactivity and molecular properties of the target compounds.
Conclusion: To predict the binding manner of the novel derivatives as antioxidants, in-silico docking study was performed on all the newly prepared compounds inside superoxide dismutase (SOD) and catalase (CAT) active site. The most active antioxidant candidate 9a (EC50 = 32.7 μM, RP50 = 52.19 μM) displayed excellent binding with Lys134 amino acid residing at Cu-Zn loop of SOD with binding energy score = -7.54 Kcal/mol, thereby increasing SOD activity and decreasing reactive oxygen species.
Keywords: 2, 2-diphenyl-1-picrylhydrazyl, reducing power, reactive oxygen species, antioxidant, docking study, synthesis.
Graphical Abstract
[1]
Becker, L.B. New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc. Res., 2004, 61(3), 461-470.
[http://dx.doi.org/10.1016/j.cardiores.2003.10.025] [PMID: 14962477]
[http://dx.doi.org/10.1016/j.cardiores.2003.10.025] [PMID: 14962477]
[2]
Wells, P.G.; Bhuller, Y.; Chen, C.S.; Jeng, W.; Kasapinovic, S.; Kennedy, J.C.; Kim, P.M.; Laposa, R.R.; McCallum, G.P.; Nicol, C.J.; Par-man, T.; Wiley, M.J.; Wong, A.W. Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol. Appl. Pharmacol., 2005, 207(2)(Suppl.), 354-366.
[http://dx.doi.org/10.1016/j.taap.2005.01.061] [PMID: 16081118]
[http://dx.doi.org/10.1016/j.taap.2005.01.061] [PMID: 16081118]
[3]
Datta, K.; Sinha, S.; Chattopadhyay, P. Reactive oxygen species in health and disease. Natl. Med. J. India, 2000, 13(6), 304-310.
[PMID: 11209486]
[PMID: 11209486]
[4]
von Bernhardi, R.; Eugenín, J. Alzheimer’s disease: Redox dysregulation as a common denominator for diverse pathogenic mechanisms. Antioxid. Redox Signal., 2012, 16(9), 974-1031.
[http://dx.doi.org/10.1089/ars.2011.4082] [PMID: 22122400]
[http://dx.doi.org/10.1089/ars.2011.4082] [PMID: 22122400]
[5]
Ortiz, G.G.; Pacheco-Moisés, F.P.; Mireles-Ramírez, M.A.; Flores-Alvarado, L.J.; González-Usigli, H.; Sánchez-López, A.L. Oxidative stress and Parkinson’s disease: Effects on environmental toxicology. In: Free Radicals and Diseases; Intech, 2016, pp. 183-209.
[6]
Fanjul-Moles, M.L.; López-Riquelme, G.O. Relationship between oxidative stress, circadian rhythms, and AMD. Oxid. Med. Cell. Longev., 2016, 2016, 7420637.
[http://dx.doi.org/10.1155/2016/7420637]
[http://dx.doi.org/10.1155/2016/7420637]
[7]
Sekeroğlu, M.R.; Sahin, H.; Dülger, H.; Algün, E. The effect of dietary treatment on erythrocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase, and serum lipid peroxidation in patients with type 2 diabetes mellitus. Clin. Biochem., 2000, 33(8), 669-674.
[http://dx.doi.org/10.1016/S0009-9120(00)00190-9] [PMID: 11166015]
[http://dx.doi.org/10.1016/S0009-9120(00)00190-9] [PMID: 11166015]
[8]
Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm. J., 2016, 24(5), 547-553.
[http://dx.doi.org/10.1016/j.jsps.2015.03.013] [PMID: 27752226]
[http://dx.doi.org/10.1016/j.jsps.2015.03.013] [PMID: 27752226]
[9]
Albano, E. Alcohol, oxidative stress and free radical damage. Proc. Nutr. Soc., 2006, 65(3), 278-290.
[http://dx.doi.org/10.1079/PNS2006496] [PMID: 16923312]
[http://dx.doi.org/10.1079/PNS2006496] [PMID: 16923312]
[10]
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]
[http://dx.doi.org/10.2174/187221309787158371] [PMID: 19149749]
[11]
Barnham, K.J.; Masters, C.L.; Bush, A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov., 2004, 3(3), 205-214.
[http://dx.doi.org/10.1038/nrd1330] [PMID: 15031734]
[http://dx.doi.org/10.1038/nrd1330] [PMID: 15031734]
[12]
Mirdamadi, S.; Mirzaei, M.; Soleymanzadeh, N.; Safavi, M.; Bakhtiari, N.; Zandi, M. Antioxidant and cytoprotective effects of synthetic peptides identified from Kluyveromyces marxianus protein hydrolysate: Insight into the molecular mechanism. Lebensm. Wiss. Technol., 2021, 148, 111792.
[http://dx.doi.org/10.1016/j.lwt.2021.111792]
[http://dx.doi.org/10.1016/j.lwt.2021.111792]
[13]
Gür, F.; Cengiz, M.; Kutlu, H.M.; Cengiz, B.P. Ayhancı; A. Molecular docking analyses of escin as regards cyclophosphamide-induced cardiotoxicity: In vivo and in silico studies. Toxicol. Appl. Pharmacol., 2021, 411, 115386.
[http://dx.doi.org/10.1016/j.taap.2020.115386] [PMID: 33383042]
[http://dx.doi.org/10.1016/j.taap.2020.115386] [PMID: 33383042]
[14]
Ighodaro, O.; Akinloye, O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med., 2018, 54, 287-293.
[http://dx.doi.org/10.1016/j.ajme.2017.09.001]
[http://dx.doi.org/10.1016/j.ajme.2017.09.001]
[15]
Karihtala, P.; Soini, Y. Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies. Acta Pathol. Microbiol. Scand. Suppl., 2007, 115(2), 81-103.
[http://dx.doi.org/10.1111/j.1600-0463.2007.apm_514.x] [PMID: 17295675]
[http://dx.doi.org/10.1111/j.1600-0463.2007.apm_514.x] [PMID: 17295675]
[16]
Xu, S.; Rouzer, C.A.; Marnett, L.J. Oxicams, a class of nonsteroidal anti-inflammatory drugs and beyond. IUBMB Life, 2014, 66(12), 803-811.
[http://dx.doi.org/10.1002/iub.1334] [PMID: 25537198]
[http://dx.doi.org/10.1002/iub.1334] [PMID: 25537198]
[17]
Defazio, S.; Cini, R. Synthesis, X-ray structural characterization and solution studies of metal complexes containing the anti-inflammatory drugs meloxicam and tenoxicam. Polyhedron, 2003, 22, 1355-1366.
[http://dx.doi.org/10.1016/S0277-5387(03)00112-8]
[http://dx.doi.org/10.1016/S0277-5387(03)00112-8]
[18]
Ashraf, A.; Kubanik, M.; Aman, F.; Holtkamp, H.; Söhnel, T.; Jamieson, S.M. RuII (η6‐p‐cymene) complexes of bioactive 1, 2‐benzothiazines: protein binding vs. antitumor activity. Eur. J. Inorg. Chem., 2016, 2016, 1376-1382.
[http://dx.doi.org/10.1002/ejic.201501361]
[http://dx.doi.org/10.1002/ejic.201501361]
[19]
Aslam, S.; Wang, F.; Ahmad, M.; Zahoor, A.F.; Mansha, A.; Rasul, A.; Fu, L. Benzothiazine based acetohydrazides and acetamides as anticancer agents. Pak. J. Pharm. Sci., 2019, 32(6)(Suppl.), 2795-2800.
[PMID: 32024616]
[PMID: 32024616]
[20]
Patel, C.; Bassin, J.P.; Scott, M.; Flye, J.; Hunter, A.P.; Martin, L.; Goyal, M. Synthesis and antimicrobial activity of 1, 2-benzothiazine derivatives. Molecules, 2016, 21(7), 861.
[http://dx.doi.org/10.3390/molecules21070861] [PMID: 27376253]
[http://dx.doi.org/10.3390/molecules21070861] [PMID: 27376253]
[21]
Malinka, W.; Gamian, A.; Berenika, S. Synthesis and studies on antibacterial activity of pyrido [3, 2-e]-1, 2-thiazines and related deriva-tives. Tuberculosis, 2008, 37, 6.
[22]
Zia-ur-Rehman. M.; Choudary, J.A.; Elsegood, M.R.; Siddiqui, H.L.; Khan, K.M. A facile synthesis of novel biologically active 4-hydroxy-N'-(benzylidene)-2H-benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxides. Eur. J. Med. Chem., 2009, 44(3), 1311-1316.
[http://dx.doi.org/10.1016/j.ejmech.2008.08.002] [PMID: 18804313]
[http://dx.doi.org/10.1016/j.ejmech.2008.08.002] [PMID: 18804313]
[23]
Szczęśniak-Sięga, B.; Gębczak, K.; Gębarowski, T.; Maniewska, J. Synthesis, COX-1/2 inhibition and antioxidant activities of new oxicam analogues designed as potential chemopreventive agents. Acta Biochim. Pol., 2018, 65(2), 199-207.
[http://dx.doi.org/10.18388/abp.2018_2614] [PMID: 29906298]
[http://dx.doi.org/10.18388/abp.2018_2614] [PMID: 29906298]
[24]
Badshah, S.L.; Naeem, A. Bioactive thiazine and benzothiazine derivatives: green synthesis methods and their medicinal importance. Molecules, 2016, 21(8), 1054.
[http://dx.doi.org/10.3390/molecules21081054] [PMID: 27537865]
[http://dx.doi.org/10.3390/molecules21081054] [PMID: 27537865]
[25]
Panga, S.S.; Tamatam, R.; Adivireddy, P.; Venkatapuram, P.; Narra, S.K.; Paturu, K. Synthesis, cytotoxic and antioxidant activities of az-olyl benzothiazine carboxamides. Res. Chem. Intermed., 2019, 45, 3053-3075.
[http://dx.doi.org/10.1007/s11164-019-03778-4]
[http://dx.doi.org/10.1007/s11164-019-03778-4]
[26]
Abdelgawad, M.A.; Bakr, R.B.; Azouz, A.A. Novel pyrimidine-pyridine hybrids: Synthesis, cyclooxygenase inhibition, anti-inflammatory activity and ulcerogenic liability. Bioorg. Chem., 2018, 77, 339-348.
[http://dx.doi.org/10.1016/j.bioorg.2018.01.028] [PMID: 29421710]
[http://dx.doi.org/10.1016/j.bioorg.2018.01.028] [PMID: 29421710]
[27]
Elkanzi, N.A.; Bakr, R.B.; Ghoneim, A.A. Design, synthesis, molecular modeling study, and antimicrobial activity of some novel pyrano [2, 3-b] pyridine and pyrrolo [2, 3-b] pyrano [2.3-d] pyridine derivatives. J. Heterocycl. Chem., 2019, 56, 406-416.
[28]
Bakr, R.B.; Elkanzi, N.A. Preparation of some novel thiazolidinones, imidazolinones, and azetidinone bearing pyridine and pyrimidine moieties with antimicrobial activity. J. Heterocycl. Chem., 2020, 57(7), 2977-2989.
[http://dx.doi.org/10.1002/jhet.4009]
[http://dx.doi.org/10.1002/jhet.4009]
[29]
Gras, M.; Therrien, B.; Süss-Fink, G.; Casini, A.; Edafe, F.; Dyson, P.J. Anticancer activity of new organo-ruthenium, rhodium and iridi-um complexes containing the 2-(pyridine-2-yl) thiazole N, N-chelating ligand. J. Organomet. Chem., 2010, 695, 1119-1125.
[http://dx.doi.org/10.1016/j.jorganchem.2010.01.020]
[http://dx.doi.org/10.1016/j.jorganchem.2010.01.020]
[30]
Elzahabi, H.S. Synthesis, characterization of some benzazoles bearing pyridine moiety: Search for novel anticancer agents. Eur. J. Med. Chem., 2011, 46(9), 4025-4034.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.075] [PMID: 21704435]
[http://dx.doi.org/10.1016/j.ejmech.2011.05.075] [PMID: 21704435]
[31]
Kelley, J.L.; Koble, C.S.; Davis, R.G.; McLean, E.W.; Soroko, F.E.; Cooper, B.R. 1-(Fluorobenzyl)-4-amino-1H-1,2,3-triazolo[4,5-c]pyridines: Synthesis and anticonvulsant activity. J. Med. Chem., 1995, 38(20), 4131-4134.
[http://dx.doi.org/10.1021/jm00020a030] [PMID: 7562950]
[http://dx.doi.org/10.1021/jm00020a030] [PMID: 7562950]
[32]
Ferrarini, P.L.; Mori, C.; Badawneh, M.; Calderone, V.; Greco, R.; Manera, C.; Martinelli, A.; Nieri, P.; Saccomanni, G. Synthesis and β-blocking activity of (R,S)-(E)-oximeethers of 2, 3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2, 3-b]pyridine: Potential anti-hypertensive agents - part IX. Eur. J. Med. Chem., 2000, 35(9), 815-826.
[http://dx.doi.org/10.1016/S0223-5234(00)00173-2] [PMID: 11006483]
[http://dx.doi.org/10.1016/S0223-5234(00)00173-2] [PMID: 11006483]
[33]
Shi, F.; Li, C.; Xia, M.; Miao, K.; Zhao, Y.; Tu, S.; Zheng, W.; Zhang, G.; Ma, N. Green chemoselective synthesis of thiazolo[3,2-a]pyridine derivatives and evaluation of their antioxidant and cytotoxic activities. Bioorg. Med. Chem. Lett., 2009, 19(19), 5565-5568.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.046] [PMID: 19729303]
[http://dx.doi.org/10.1016/j.bmcl.2009.08.046] [PMID: 19729303]
[34]
Al-Omar, M.A.; Youssef, K.M.; El-Sherbeny, M.A.; Awadalla, S.A.A.; El-Subbagh, H.I. Synthesis and in vitro antioxidant activity of some new fused pyridine analogs. Arch. Pharm. (Weinheim), 2005, 338(4), 175-180.
[http://dx.doi.org/10.1002/ardp.200400953] [PMID: 15864787]
[http://dx.doi.org/10.1002/ardp.200400953] [PMID: 15864787]
[35]
Kaddouri, Y.; Abrigach, F.; Yousfi, E.B.; El Kodadi, M.; Touzani, R. New thiazole, pyridine and pyrazole derivatives as antioxidant can-didates: Synthesis, DFT calculations and molecular docking study. Heliyon, 2020, 6(1), e03185.
[http://dx.doi.org/10.1016/j.heliyon.2020.e03185] [PMID: 31956713]
[http://dx.doi.org/10.1016/j.heliyon.2020.e03185] [PMID: 31956713]
[36]
Elkanzi, N.A.; Hrichi, H.; Bakr, R.B.; Hendawy, O.; Alruwaili, M.M.; Alruwaili, E.D. Synthesis, in vitro evaluation and molecular docking of new pyrazole derivatives bearing 1, 5, 10, 10a-tetrahydrobenzo [g] quinoline-3-carbonitrile moiety as potent antibacterial agents. J. Iran. Chem. Soc., 2021, 18, 977-991.
[37]
Ghoneim, A.A.; Ahmed Elkanzi, N.A.; Bakr, R.B. Synthesis and studies molecular docking of some new thioxobenzo [g] pteridine deriva-tives and 1, 4-dihydroquinoxaline derivatives with glycosidic moiety. J. Taibah Univ. Sci., 2018, 12, 774-782.
[http://dx.doi.org/10.1080/16583655.2018.1510163]
[http://dx.doi.org/10.1080/16583655.2018.1510163]
[38]
Al-Sanea, M.M.; Elkamhawy, A.; Paik, S.; Lee, K.; El Kerdawy, A.M.; Syed Nasir Abbas, B.; Joo Roh, E.; Eldehna, W.M.; Elshemy, H.A.H.; Bakr, R.B.; Ali Farahat, I.; Alzarea, A.I.; Alzarea, S.I.; Alharbi, K.S.; Abdelgawad, M.A. Sulfonamide-based 4-anilinoquinoline de-rivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights. Bioorg. Med. Chem., 2020, 28(13), 115525.
[http://dx.doi.org/10.1016/j.bmc.2020.115525] [PMID: 32371117]
[http://dx.doi.org/10.1016/j.bmc.2020.115525] [PMID: 32371117]
[39]
Al-Sanea, M.; Parambi, D.; Shaker, M.; Elsherif, H.; Elshemy, H.; Bakr, R. Design, synthesis, and in vitro cytotoxic activity of certain 2-[3-phenyl-4-(pyrimidin-4-yl)-1 h-pyrazol1-yl] acetamide derivatives. Russ. J. Org. Chem., 2020, 56, 514-520.
[http://dx.doi.org/10.1134/S1070428020030239]
[http://dx.doi.org/10.1134/S1070428020030239]
[40]
Hrichi, H.; Ahmed, E.N.A.; Badawy, B.R. Novel β-lactams and thiazolidinone derivatives from 1, 4-dihydroquinoxaline schiff’s base: synthesis, antimicrobial activity and molecular docking studies. Chem. J. Moldova, 2020, 15, 86-94.
[http://dx.doi.org/10.19261/cjm.2019.647]
[http://dx.doi.org/10.19261/cjm.2019.647]
[41]
Abdelall, E.; Bakr, R.; Abdel-Hamid, M.; Kandeel, M. Enhancement to synthesize, design and dock of novel EGFR inhibitors containing pyrazolo [3, 4-d] pyrimidine cores of expected anticancer activity. OCAIJ, 2014, 10, 470-483.
[42]
Bakr, R.B.; Mehany, A. (3, 5-Dimethylpyrazol-1-yl)-[4-(1-phenyl-1H-pyrazolo [3, 4-d] pyrimidin-4-ylamino) phenyl] methanone. Molbank, 2016, 2016, M915.
[http://dx.doi.org/10.3390/M915]
[http://dx.doi.org/10.3390/M915]
[43]
El Azab, I.H.; Bakr, R.B.; Elkanzi, N.A.A. Facile one-pot multicomponent synthesis of pyrazolo-thiazole substituted pyridines with poten-tial anti-proliferative activity: Synthesis, in vitro and in silico studies. Molecules, 2021, 26(11), 3103.
[http://dx.doi.org/10.3390/molecules26113103] [PMID: 34067399]
[http://dx.doi.org/10.3390/molecules26113103] [PMID: 34067399]
[44]
Abdelgawad, M.A.; Musa, A.; Almalki, A.H.; Alzarea, S.I.; Mostafa, E.M.; Hegazy, M.M.; Mostafa-Hedeab, G.; Ghoneim, M.M.; Parambi, D.G.T.; Bakr, R.B.; Al-Muaikel, N.S.; Alanazi, A.S.; Alharbi, M.; Ahmad, W.; Bukhari, S.N.A.; Al-Sanea, M.M. Novel phenolic com-pounds as potential dual egfr and cox-2 inhibitors: design, semisynthesis, in vitro biological evaluation and in silico insights. Drug Des. Devel. Ther., 2021, 15, 2325-2337.
[http://dx.doi.org/10.2147/DDDT.S310820] [PMID: 34103896]
[http://dx.doi.org/10.2147/DDDT.S310820] [PMID: 34103896]
[45]
Abdellatif, K.R.; Bakr, R.B. Pyrimidine and fused pyrimidine derivatives as promising protein kinase inhibitors for cancer treatment. Med. Chem. Res., 2021, 30, 31-49.
[46]
Bakr, R.B.; Azab, I.H.E.; Elkanzi, N.A. Thiochromene candidates:
Design, synthesis, antimicrobial potential and in silico docking
study. J. Iran. Chem. Soc., 2021. Available from:
[http://dx.doi.org/10.1007/s13738-021-02391-w]
[http://dx.doi.org/10.1007/s13738-021-02391-w]
[48]
Burda, S.; Oleszek, W. Antioxidant and antiradical activities of flavonoids. J. Agric. Food Chem., 2001, 49(6), 2774-2779.
[http://dx.doi.org/10.1021/jf001413m] [PMID: 11409965]
[http://dx.doi.org/10.1021/jf001413m] [PMID: 11409965]
[49]
Vukovic, N.; Sukdolak, S.; Solujic, S.; Niciforovic, N. An efficient synthesis and antioxidant properties of novel imino and amino deriva-tives of 4-hydroxy coumarins. Arch. Pharm. Res., 2010, 33(1), 5-15.
[http://dx.doi.org/10.1007/s12272-010-2220-z] [PMID: 20191339]
[http://dx.doi.org/10.1007/s12272-010-2220-z] [PMID: 20191339]
[50]
Dinis, T.C.; Maderia, V.M.; Almeida, L.M. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch. Biochem. Biophys., 1994, 315(1), 161-169.
[http://dx.doi.org/10.1006/abbi.1994.1485] [PMID: 7979394]
[http://dx.doi.org/10.1006/abbi.1994.1485] [PMID: 7979394]
[51]
Ak, T.; Gülçin, I. Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact., 2008, 174(1), 27-37.
[http://dx.doi.org/10.1016/j.cbi.2008.05.003] [PMID: 18547552]
[http://dx.doi.org/10.1016/j.cbi.2008.05.003] [PMID: 18547552]
[52]
Gülçin, İ.; Elias, R.; Gepdiremen, A.; Taoubi, K.; Köksal, E. Antioxidant
secoiridoids from fringe tree. (Chionanthus virginicus L.).
Wood Sci. Technols., 2009, 43, 195.
[http://dx.doi.org/10.1007/s00226-008-0234-1]
[http://dx.doi.org/10.1007/s00226-008-0234-1]
[53]
Gouet, P.; Jouve, H-M.; Williams, P.A.; Andersson, I.; Andreoletti, P.; Nussaume, L.; Hajdu, J. Ferryl intermediates of catalase captured by time-resolved Weissenberg crystallography and UV-VIS spectroscopy. Nat. Struct. Biol., 1996, 3(11), 951-956.
[http://dx.doi.org/10.1038/nsb1196-951] [PMID: 8901874]
[http://dx.doi.org/10.1038/nsb1196-951] [PMID: 8901874]
[54]
Theppawong, A.; Van de Walle, T.; Grootaert, C.; Bultinck, M.; Desmet, T.; Van Camp, J.; D’hooghe, M. Synthesis of novel aza-aromatic curcuminoids with improved biological activities towards various cancer cell lines. ChemistryOpen, 2018, 7(5), 381-392.
[http://dx.doi.org/10.1002/open.201800029] [PMID: 29872613]
[http://dx.doi.org/10.1002/open.201800029] [PMID: 29872613]
[55]
Abdelgawad, M.A.; Bakr, R.B.; Ahmad, W.; Al-Sanea, M.M.; Elshemy, H.A.H. New pyrimidine-benzoxazole/benzimidazole hybrids: Syn-thesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition. Bioorg. Chem., 2019, 92, 103218.
[http://dx.doi.org/10.1016/j.bioorg.2019.103218] [PMID: 31536956]
[http://dx.doi.org/10.1016/j.bioorg.2019.103218] [PMID: 31536956]
[56]
Arya, K.; Tomar, P.; Singh, J. Design, synthesis and biological evaluation of novel spiro [indole-pyridothiazine] analogs as antiprolifera-tive agents. RSC Advances, 2014, 4, 3060-3064.
[http://dx.doi.org/10.1039/C3RA43908A]
[http://dx.doi.org/10.1039/C3RA43908A]
[57]
Schade, B.; Studenik, C. Effects of novel pyridothiazepines and pyridothiazines on contractility of isolated guinea-pig heart muscle and vascular smooth muscle preparations. Biol. Pharm. Bull., 1999, 22(7), 683-686.
[http://dx.doi.org/10.1248/bpb.22.683] [PMID: 10443462]
[http://dx.doi.org/10.1248/bpb.22.683] [PMID: 10443462]
[58]
Malinka, W.; Sieklucka-Dziuba, M.; Rajtar-Cynke, G.; Borowicz, K.; Kleinrok, Z. Studies on synthesis and biological properties of
pyrazolo [4, 3-c]-pyrido [3, 2-e]-1, 2-thiazine-5, 5-dioxide bearing
4-substituted-1-piperazinylpropyl moiety. Farmaco (Societa chimica
italiana: 1989), 1994, 49, 783-792.
[59]
Zawisza, T.; Malinka, W. A novel system: 2H-pyrido[3,2-e]-1,2-thiazine-1,1-dioxide. Synthesis and properties of some derivatives. Farmaco, Sci., 1986, 41(10), 819-826.
[PMID: 3792541]
[PMID: 3792541]
[60]
Szczukowski, Ł.; Krzyżak, E.; Zborowska, A.; Zając, P.; Potyrak, K.; Peregrym, K.; Wiatrak, B.; Marciniak, A.; Świątek, P. Design, syn-thesis and comprehensive investigations of pyrrolo[3,4-d]pyridazinone-based 1,3,4-oxadiazole as new class of selective COX-2 inhibi-tors. Int. J. Mol. Sci., 2020, 21(24), 9623.
[http://dx.doi.org/10.3390/ijms21249623] [PMID: 33348757]
[http://dx.doi.org/10.3390/ijms21249623] [PMID: 33348757]
[61]
Youssef, A.M.; Azab, M.E.; Youssef, M.M. Bromination and diazo-coupling of pyridinethiones; microwave assisted synthesis of isothia-zolopyridine, pyridothiazine and pyridothiazepines. Molecules, 2012, 17(6), 6930-6943.
[http://dx.doi.org/10.3390/molecules17066930] [PMID: 22728367]
[http://dx.doi.org/10.3390/molecules17066930] [PMID: 22728367]
[62]
Al-Rashood, S.T.; Hamed, A.R.; Hassan, G.S.; Alkahtani, H.M.; Almehizia, A.A.; Alharbi, A.; Al-Sanea, M.M.; Eldehna, W.M. Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 831-839.
[http://dx.doi.org/10.1080/14756366.2020.1743281] [PMID: 32208781]
[http://dx.doi.org/10.1080/14756366.2020.1743281] [PMID: 32208781]
[63]
Drăgan, M.; Stan, C.D.; Pânzariu, A.; Profire, L. Assessment of in vitro antioxidant and antiinflamatory activities of new azetidin-2-ones derivatives of ferulic acid. Farmacia, 2016, 64, 717-721.
[64]
Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30(1), 11-26.
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[65]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
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