Generic placeholder image

Medicinal Chemistry

Author(s): Nenad Joksimović*, Jelena Petronijević, Emilija Milović, Nenad Janković, Marijana Kosanić and Nevena Petrović

DOI: 10.2174/1573406418666220304230342

DownloadDownload PDF Flyer Cite As
Antioxidant and Antimicrobial Potential, BSA and DNA Binding Properties of Some 3-Hydroxy-3-Pyrrolin-2-Ones Bearing Thenoyl Fragment

Page: [784 - 790] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: It is known that pyrrolidinone derivates belong to a class of biologically active compounds with a broad spectrum of biological actions. Nowadays, many scientists are making an effort in the discovery of more effective ways to eliminate reactive oxygen species (ROS) that cause oxidative stress or to eliminate the harmful microorganisms from the organism in humans. Therefore, pyrrolidinones seem to be great candidates for the research of this field.

Methods: The antimicrobial activity of tested compounds was estimated by the determination of the minimal inhibitory concentration by the broth micro-dilution method against four species of bacteria and five species of fungi. The antioxidant activity was evaluated by free radical scavenging and reducing power.

Results: Among the tested compounds, P22 showed marked antibacterial activity on Staphylococcus aureus with a MIC value of 0.312 mg/mL. Maximum antifungal activity with MIC value 0.625 mg/mL was shown by P23 and P25 compounds against Trichophyton mentagrophytes. Tested samples showed a relatively strong scavenging activity on DPPH radical (IC50 ranged from 166.75- 727.17 μg/mL). The strongest DPPH radical scavenging activity was shown by P3 compound with an IC50 value of 166.75 μg/mL. Moreover, the tested compounds had effective reducing power. Compounds P3, P10, and P13 showed the highest reducing power than those from the other samples. Results of the interactions between DNA and P3 indicated that P3 had the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (1.4 ± 0.1) × 105 M-1], while Ka values obtained via titration of BSA with P23 or P25 [Ka = (6.2 ± 0.2) and (5.0 ± 0.2) × 105 M-1] indicate that the notable quantity of the drug can be transmitted to the cells.

Conclusion: Achieved results indicate that our compounds are potential candidates for use as medicaments.

Keywords: 3-hydroxy-3-pyrrolin-2-ones, biological evaluation, antimicrobial activity, antioxidant activity, DNA binding study, BSA binding study.

Graphical Abstract

[1]
Sas, K.; Robotka, H.; Toldi, J.; Vécsei, L. Mitochondria, met-abolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J. Neurol. Sci., 2007, 257(1-2), 221-239.
[http://dx.doi.org/10.1016/j.jns.2007.01.033] [PMID: 17462670]
[2]
Bolton, J.L.; Trush, M.A.; Penning, T.M.; Dryhurst, G.; Monks, T.J. Role of quinones in toxicology. Chem. Res. Toxicol., 2000, 13(3), 135-160.
[http://dx.doi.org/10.1021/tx9902082] [PMID: 10725110]
[3]
Upston, J.M.; Kritharides, L.; Stocker, R. The role of vitamin E in atherosclerosis. Prog. Lipid Res., 2003, 42(5), 405-422.
[http://dx.doi.org/10.1016/S0163-7827(03)00024-9] [PMID: 12814643]
[4]
Smith, M.A.; Rottkamp, C.A.; Nunomura, A.; Raina, A.K.; Perry, G. Oxidative stress in Alzheimer’s disease. Biochim. Biophys. Acta, 2000, 1502(1), 139-144.
[http://dx.doi.org/10.1016/S0925-4439(00)00040-5] [PMID: 10899439]
[5]
Guidi, I.; Galimberti, D.; Lonati, S.; Novembrino, C.; Bamonti, F.; Tiriticco, M.; Fenoglio, C.; Venturelli, E.; Baron, P.; Bresolin, N.; Scarpini, E. Oxidative imbalance in patients with mild cognitive impairment and Alzheimer’s disease. Neurobiol. Aging, 2006, 27(2), 262-269.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.01.001] [PMID: 16399211]
[6]
Singh, U.; Jialal, I. Oxidative stress and atherosclerosis. Pathophysiology, 2006, 13(3), 129-142.
[http://dx.doi.org/10.1016/j.pathophys.2006.05.002] [PMID: 16757157]
[7]
Arteel, G.E. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology, 2003, 124(3), 778-790.
[http://dx.doi.org/10.1053/gast.2003.50087] [PMID: 12612915]
[8]
Ramakrishna, B.S.; Varghese, R.; Jayakumar, S.; Mathan, M.; Balasubramanian, K.A. Circulating antioxidants in ulcerative colitis and their relationship to disease severity and activity. J. Gastroenterol. Hepatol., 1997, 12(7), 490-494.
[http://dx.doi.org/10.1111/j.1440-1746.1997.tb00471.x] [PMID: 9257238]
[9]
Kinnula, V.L.; Crapo, J.D. Superoxide dismutases in malignant cells and human tumors. Free Radic. Biol. Med., 2004, 36(6), 718-744.
[http://dx.doi.org/10.1016/j.freeradbiomed.2003.12.010] [PMID: 14990352]
[10]
Mohan, C.S.; Balamurugan, V.; Elayara, R.; Prabakaran, A.S. Antioxidant and photochemical potential of medicinal plant Kalanchoe pinnata. Int. J. Pharm. Sci. Res., 2012, 3, 881-885.
[11]
Joksimović, N.; Baskić, D.; Popović, S.; Zarić, M.; Kosanić, M.; Ranković, B.; Stanojković, T.; Novaković, S.B.; Davidović, G.; Bugarčić, Z.; Janković, N. Synthesis, characterization, biological activity, DNA and BSA binding study: Novel cop-per(ii) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. Dalton Trans., 2016, 45(38), 15067-15077.
[http://dx.doi.org/10.1039/C6DT02257J] [PMID: 27711668]
[12]
Joksimović, N.; Petronijević, J.; Janković, N.; Kosanić, M.; Milivojević, D.; Vraneš, M.; Tot, A.; Bugarčić, Z. Synthesis, characterization, antioxidant activity of β-diketonates, and ef-fects of coordination to copper(II) ion on their activity: DNA, BSA interactions and molecular docking study. Med. Chem., 2021, 17(5), 519-532.
[http://dx.doi.org/10.2174/1573406415666191024102520] [PMID: 31696810]
[13]
Zhang, W.; Liu, J.; Macho, J.M.; Jiang, X.; Xie, D.; Jiang, F.; Liu, W.; Fu, L. Design, synthesis and antimicrobial evaluation of novel benzoxazole derivatives. Eur. J. Med. Chem., 2017, 126, 7-14.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.010] [PMID: 27744188]
[14]
Gein, V.L.; Odegova, T.F.; Rogachev, S.N.; Bobyleva, A.A.; Gein, L.F. Synthesis and antimicrobial activity of 5-aryl-4-acyl-3-hydroxy-1-[2-(3-hidrohyethoxy)-ethyl]-3-pyrrolin-2-ones. Pharm. Chem. J., 2015, 49, 175-177.
[http://dx.doi.org/10.1007/s11094-015-1248-2]
[15]
Shah, S.S.A.; Rivera, G.; Ashfaq, M. Recent advances in me-dicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents. Mini Rev. Med. Chem., 2013, 13(1), 70-86.
[http://dx.doi.org/10.2174/138955713804484749] [PMID: 22625411]
[16]
Shah, S.S.A.; Ashfaq, M.; Waseem, A.; Ahmed, M.M.; Najam, T.; Shaheen, S.; Rivera, G. Synthesis and biological activities of organotin(IV) complexes as antitumoral and antimicrobial agents. A review. Mini Rev. Med. Chem., 2015, 15(5), 406-426.
[http://dx.doi.org/10.2174/138955751505150408142958] [PMID: 25910654]
[17]
Ahmad, K.; Naseem, H.A.; Parveen, S. H.-ur, R.; ShahS.S, A.; Shaheen, S.; Ashfaq, A.; Jamil, J.; Ahmad, M.M.; Ashfaq, M. Synthesis and spectroscopic characterization of medicinal azo derivatives and metal complexes of indandion. J. Mol. Struct., 2019, 1198, 126885-126893.
[http://dx.doi.org/10.1016/j.molstruc.2019.126885]
[18]
Chiosis, G.; Caldas Lopes, E.; Solit, D. Heat shock protein-90 inhibitors: A chronicle from geldanamycin to today’s agents. Curr. Opin. Investig. Drugs, 2006, 7(6), 534-541.
[PMID: 16784024]
[19]
Gein, V.L.; Platonov, V.S.; Voronina, É.V. Synthesis and antimicrobial activity of 1,5-diaryl-4-heteroyl-3-hodroxy-3-pirolin-2-ones. Pharm. Chem. J., 2004, 38, 316-318.
[http://dx.doi.org/10.1023/B:PHAC.0000048143.40360.9c]
[20]
Gein, V.L.; Mihalev, V.A.; Kasimova, N.N.; Voronina, E.V.; Vakhrin, M.I.; Babushkina, E.B. Synthesis and antibacterial activity of 1-alxoxyalkyl-5-aryl-4-acyl-3-hydroxy-3-pyrrolin-2-ones. Pharm. Chem. J., 2007, 41, 208-210.
[http://dx.doi.org/10.1007/s11094-007-0047-9]
[21]
Gein, V.L.; Bobyleva, A.A.; Levandovskaya, E.B.; Odegova, T.F.; Vakhrin, M.I. Synthesis and antimicrobial activity of 5-aryl-4-acyl(heteroyl)-3-hydroxy-1-(3-ethoxypropyl)-3-pyrrolin-2-ones. Pharm. Chem. J., 2012, 46, 23-25.
[http://dx.doi.org/10.1007/s11094-012-0728-x]
[22]
Joksimović, N.; Petronijević, J.; Janković, N.; Baskić, D.; Popović, S.; Todorović, D.; Matić, S.; Bogdanović, G.A.; Vraneš, M.; Tot, A.; Bugarčić, Z. Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study. Bioorg. Chem., 2019, 88, 102954-102986.
[http://dx.doi.org/10.1016/j.bioorg.2019.102954] [PMID: 31054428]
[23]
Gein, V.L.; Shumilovskikh, E.V.; Andreichikov, Yu.S.; Saraeva, R.F.; Korobchenko, L.V.; Vladyko, G.V.; Boreko, E.I. Synthesis of 4-substituted 1-methyl-5-aryl- and 1,5-diaryltetrahydropyrrole-2,3-diones and their antiviral action. Pharm. Chem. J., 1991, 25, 884-887.
[http://dx.doi.org/10.1007/BF00778979]
[24]
Gein, V.L.; Voronina, O.V.; Ryumina, T.E.; Novoselova, G.N.; Potemkin, K.D.; Andreichikov, Y.S. Synthesis and an-timicrobial activity of 1,5-diaryl-3-hydroxy-2-oxo-3-pyrroline-4-carboxylic acids and their derivatives. Pharm. Chem. J., 1996, 30, 95-96.
[http://dx.doi.org/10.1007/BF02218875]
[25]
Gein, V.L.; Popov, A.V.; Kolla, V.É.; Popova, N.A. Synthesis and biological activity of 1,5-diaryl-3-arylamino-4-carboxymethyl-2,5-dihydro-2-pyrrolones and 1,5-diaryl-4-carboxymethyltetrahydropyrrole-2, 3-diones. Pharm. Chem. J., 1993, 27, 343-346.
[http://dx.doi.org/10.1007/BF00819965]
[26]
Brown, C.S.; Lee, M.S.; Leung, D.W.; Wang, T.; Xu, W.; Luthra, P.; Anantpadma, M.; Shabman, R.S.; Melito, L.M.; MacMillan, K.S.; Borek, D.M.; Otwinowski, Z.; Ramanan, P.; Stubbs, A.J.; Peterson, D.S.; Binning, J.M.; Tonelli, M.; Ol-son, M.A.; Davey, R.A.; Ready, J.M.; Basler, C.F.; Amara-singhe, G.K. In silico derived small molecules bind the filo-virus VP35 protein and inhibit its polymerase cofactor activity. J. Mol. Biol., 2014, 426(10), 2045-2058.
[http://dx.doi.org/10.1016/j.jmb.2014.01.010] [PMID: 24495995]
[27]
Zhao, Y.; Wang, Q.; Meng, Q.; Ding, D.; Yang, H.; Gao, G.; Li, D.; Zhu, W.; Zhou, H. Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis. Bioorg. Med. Chem., 2012, 20(3), 1240-1250.
[http://dx.doi.org/10.1016/j.bmc.2011.12.035] [PMID: 22249121]
[28]
Starosyla, S.A.; Volynets, G.P.; Lukashov, S.S.; Gorbatiuk, O.B.; Golub, A.G.; Bdzhola, V.G.; Yarmoluk, S.M. Identifica-tion of apoptosis signal-regulating kinase 1 (ASK1) inhibitors among the derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one. Bioorg. Med. Chem., 2015, 23(10), 2489-2497.
[http://dx.doi.org/10.1016/j.bmc.2015.03.056] [PMID: 25882527]
[29]
Zimmerman, S.S.; Khatri, A.; Garnier-Amblard, E.C.; Mul-lasseril, P.; Kurtkaya, N.L.; Gyoneva, S.; Hansen, K.B.; Traynelis, S.F.; Liotta, D.C. Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective po-tentiators. J. Med. Chem., 2014, 57(6), 2334-2356.
[http://dx.doi.org/10.1021/jm401695d] [PMID: 24512267]
[30]
Joksimović, N.; Petronijević, J.; Milović, E.; Janković, N.; Baskić, D.; Popović, S.; Todorović, D.; Matić, S.; Vraneš, M.; Tot, A. Synthesis, characterization, antitumor potential, BSA and DNA binding properties, and molecular docking study of some novel 3-hydroxy-3-pyrrolin-2-ones. Med. Chem., 2021.
[http://dx.doi.org/10.2174/1573406417666210803094127] [PMID: 34344294]
[31]
Burmudzija, A.; Ratković, Z.; Muškinja, J.; Janković, N.; Ranković, B.; Kosanić, M.; Đorđević, S. Ferrocenyl based py-razoline derivatives with vanillic core: Synthesis and investi-gation of their biological properties. RSC Advances, 2016, 6, 91420-91430.
[http://dx.doi.org/10.1039/C6RA18977F]
[32]
Joksimović, N.; Janković, N.; Petronijević, J.; Baskić, D.; Popovic, S.; Todorović, D.; Zarić, M.; Klisurić, O.; Vraneš, M.; Tot, A.; Bugarčić, Z. Synthesis, anticancer evaluation and synergistic effects with cisplatin of novel palladium complex-es: DNA, BSA interactions and molecular docking study. Med. Chem., 2020, 16(1), 78-92.
[http://dx.doi.org/10.2174/1573406415666190128095732] [PMID: 30686264]
[33]
Kandagal, P.B.; Ashoka, S.; Seetharamappa, J.; Shaikh, S.M.; Jadegoud, Y.; Ijare, O.B. Study of the interaction of an anti-cancer drug with human and bovine serum albumin: Spectro-scopic approach. J. Pharm. Biomed. Anal., 2006, 41(2), 393-399.
[http://dx.doi.org/10.1016/j.jpba.2005.11.037] [PMID: 16413740]
[34]
Dorman, H.J.; Bachmayer, O.; Kosar, M.; Hiltunen, R. Anti-oxidant properties of aqueous extracts from selected Lami-aceae species grown in Turkey. J. Agric. Food Chem., 2004, 52(4), 762-770.
[http://dx.doi.org/10.1021/jf034908v] [PMID: 14969528]
[35]
Oyaizu, M. Studies on products of browning reaction prepared from glucoseamine. Jpn. J. Nutr., 1986, 44, 307-314.
[http://dx.doi.org/10.5264/eiyogakuzashi.44.307]
[36]
Pfaller, M.A. National Committee for Clinical Laboratory Standards. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Conidium-Forming Filamentous Fungi: Proposed Standard; NCCLS: Wayne, PA, USA, 1998.
[37]
Sarker, S.D.; Nahar, L.; Kumarasamy, Y. Microtitre plate-based antibacterial assay incorporating resazurin as an indica-tor of cell growth, and its application in the in vitro antibacterial screening of phytochemicals. Methods, 2007, 42(4), 321-324.
[http://dx.doi.org/10.1016/j.ymeth.2007.01.006] [PMID: 17560319]
[38]
Güllçin, I. Daştan, A. Synthesis of dimeric phenol derivatives and determination of in vitro antioxidant and radical scaveng-ing activities. J. Enzyme Inhib. Med. Chem., 2007, 22(6), 685-695.
[http://dx.doi.org/10.1080/14756360601164903] [PMID: 18237020]
[39]
Muškinja, J.; Burmudžija, A.; Ratković, Z.; Ranković, B.; Kosanić, M.; Bogdanović, G.A.; Novaković, S.B. Ferrocenyl chalcones with O-alkylated vanillins: Synthesis, spectral char-acterization, microbiological evaluation, and single-crystal X-ray analysis. Med. Chem. Res., 2016, 25, 1744-1753.
[http://dx.doi.org/10.1007/s00044-016-1609-8]
[40]
Lakowicz, J.R.; Weber, G. Quenching of fluorescence by oxygen. A probe for structural fluctuations in macromole-cules. Biochemistry, 1973, 12(21), 4161-4170.
[http://dx.doi.org/10.1021/bi00745a020] [PMID: 4795686]
[41]
Petronijević, J.; Janković, N.; Stanojković, T.P.; Joksimović, N.; Grozdanić, N.Đ.; Vraneš, M.; Tot, A.; Bugarčić, Z. Biolog-ical evaluation of selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: Molecular docking study. Arch. Pharm., 2018, 35(1), e1700308.