Generic placeholder image

Letters in Drug Design & Discovery

Author(s): Adebayo Tajudeen Bale, Uzma Salar, Khalid Mohammed Khan*, Sridevi Chigurupati, Tolulope Fasina, Farman Ali, Muhammad Ali, Sitansu Sekhar Nanda, Muhammad Taha and Shahnaz Perveen

DOI: 10.2174/1570180817999201001155032

DownloadDownload PDF Flyer Cite As
Chalcones and Bis-Chalcones Analogs as DPPH and ABTS Radical Scavengers

Page: [249 - 257] Pages: 9

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: A number of synthetic scaffolds, along with natural products, have been identified as potent antioxidants. The present study deals with the evaluation of varyingly substituted, medicinally distinct class of compounds “chalcones and bis-chalcones” for their antioxidant potential.

Methods: In vitro radical scavenging activities were performed on a series of synthetic chalcones 1- 13 and bis-chalcones 14-18.

Results: All molecules 1-18 revealed a pronounced 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals scavenging potential in the ranges of IC50s = 0.58 ± 0.14 - 1.72 ± 0.03 and 0.49 ± 0.3 - 1.48 ± 0.06 μM, respectively. Ascorbic acid (IC50s = 0.5 ± 0.1 and 0.46 ± 0.17 μM for DPPH and ABTS, respectively) was used as a standard radical scavenger.

Conclusion: Structure-activity relationship (SAR) revealed an active participation of various groups, including -SMe and -OMe in scavenging activity.

Keywords: Chalcones, bis-chalcones, reactive oxygen species (ROS), DPPH, ABTS, in vitro.

Graphical Abstract

[1]
Chandrasekara, A.; Shahidi, F. Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species. J. Agric. Food Chem., 2011, 59(1), 428-436.
[http://dx.doi.org/10.1021/jf103896z] [PMID: 21133411]
[2]
Halliwell, B.; Gutteridge, J.M.C. Free Radicals in Biology and Medicine; Oxford University Press: Oxford, 1989, pp. 1-81.
[3]
Lander, H.M. An essential role for free radicals and derived species in signal transduction. FASEB J., 1997, 11(2), 118-124.
[http://dx.doi.org/10.1096/fasebj.11.2.9039953] [PMID: 9039953]
[4]
Kehrer, J.P. Free radicals as mediators of tissue injury and disease. Crit. Rev. Toxicol., 1993, 23(1), 21-48.
[http://dx.doi.org/10.3109/10408449309104073] [PMID: 8471159]
[5]
Valko, M.; Rhodes, C.J.; Moncol, J.; Izakovic, M.; Mazur, M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact., 2006, 160(1), 1-40.
[http://dx.doi.org/10.1016/j.cbi.2005.12.009] [PMID: 16430879]
[6]
Zheng, M.; Storz, G. Redox sensing by prokaryotic transcription factors. Biochem. Pharmacol., 2000, 59(1), 1-6.
[http://dx.doi.org/10.1016/S0006-2952(99)00289-0] [PMID: 10605928]
[7]
Dröge, W. Free radicals in the physiological control of cell function. Physiol. Rev., 2002, 82(1), 47-95.
[http://dx.doi.org/10.1152/physrev.00018.2001] [PMID: 11773609]
[8]
Blois, M.S. Antioxidant determinations by the use of a stable free radical. Nature, 1958, 181, 1199-1200.
[http://dx.doi.org/10.1038/1811199a0]
[9]
Ikram, M.; Rehman, S.; Khan, A.; Baker, R.J.; Hofer, T.S.; Subhan, F.; Schulzke, C. Synthesis, characterization, antioxidant and selective xanthine oxidase inhibitory studies of transition metal complexes of novel amino acid bearing Schiff base ligand. Inorg. Chim. Acta, 2015, 428, 117-126.
[http://dx.doi.org/10.1016/j.ica.2015.01.021]
[10]
Beena; Kumar, D.; Rawat, D.S. Synthesis and antioxidant activity of thymol and carvacrol based Schiff bases. Bioorg. Med. Chem. Lett., 2013, 23(3), 641-645.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.001] [PMID: 23273412]
[11]
Pillai, R.R.; Karrouchi, K.; Fettach, S.; Armaković, S.; Armaković, S.J.; Brik, Y.; Ansar, M.H. Synthesis, spectroscopic characterization, reactive properties by DFT calculations, molecular dynamics simulations and biological evaluation of Schiff bases tethered 1, 2, 4-triazole and pyrazole rings. J. Mol. Struct., 2019, 1177, 47-54.
[http://dx.doi.org/10.1016/j.molstruc.2018.09.037]
[12]
Cantuti-Castelvetri, I.; Shukitt-Hale, B.; Joseph, J.A. Neurobehavioral aspects of antioxidants in aging. Int. J. Dev. Neurosci., 2000, 18(4-5), 367-381.
[http://dx.doi.org/10.1016/S0736-5748(00)00008-3] [PMID: 10817921]
[13]
Özdemir, Ö. Studies on phenol-keto tautomerism, metal ion binding, and free radical scavenging properties of newly synthesized naphthalene-based tetraimine Schiff base. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 2018, 20, 109-123.
[14]
Ahad, G.; Khan, M.; Khan, A.; Ibrahim, M.; Salar, U. Kanwal; Khan, K. M.; Perveen, S. Synthesis, structural characterization, and antioxidant activities of 2,4-dinitrophenyl-hydrazone derivatives. J. Chem. Soc. Pak., 2018, 40, 961-973.
[15]
Ajaib, M.; Almas, M.; Khan, K.M.; Perveen, S.; Shah, S. Phytochemical screening, antimicrobial and antioxidant activities of Ficus natalensis. J. Chem. Soc. Pak., 2016, 38, 345-351.
[16]
Ajaib, M.; Arooj, T.; Khan, K.M.; Farid, S.; Ishtiaq, M.; Perveen, S.; Shah, S. Phytochemical, antimicrobial and antioxidant screening of fruits, bark and leaves of Lagerstroemia indica. J. Chem. Soc. Pak., 2016, 38, 538-545.
[17]
Darley-Usmar, V.; Halliwell, B. Blood radicals: Reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. Pharm. Res., 1996, 13(5), 649-662.
[http://dx.doi.org/10.1023/A:1016079012214] [PMID: 8860419]
[18]
Cutler, R.G. Human longevity and aging: possible role of reactive oxygen species. Ann. N. Y. Acad. Sci., 1991, 621, 1-28.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb16965.x] [PMID: 1859082]
[19]
Anderson, K.M.; Seed, T.; Ou, D.; Harris, J.E. Free radicals and reactive oxygen species in programmed cell death. Med. Hypotheses, 1999, 52(5), 451-463.
[http://dx.doi.org/10.1054/mehy.1997.0521] [PMID: 10416954]
[20]
Laird, T. Ullmann’s encyclopedia of industrial chemistry; VCH: Weinheim, Germany, 1997, p. 8.
[21]
Di Carlo, G.; Mascolo, N.; Izzo, A.A.; Capasso, F. Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci., 1999, 65(4), 337-353.
[http://dx.doi.org/10.1016/S0024-3205(99)00120-4] [PMID: 10421421]
[22]
Morel, I.; Lescoat, G.; Cogrel, P.; Sergent, O.; Pasdeloup, N.; Brissot, P.; Cillard, P.; Cillard, J. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem. Pharmacol., 1993, 45(1), 13-19.
[http://dx.doi.org/10.1016/0006-2952(93)90371-3] [PMID: 8424806]
[23]
Dhar, D.N. The chemistry of chalcones and related compounds; John Wiley: New York, 1981.
[24]
Zhuang, C.; Zhang, W.; Sheng, C.; Zhang, W.; Xing, C.; Miao, Z. Chalcone: A privileged structure in medicinal chemistry. Chem. Rev., 2017, 117(12), 7762-7810.
[http://dx.doi.org/10.1021/acs.chemrev.7b00020] [PMID: 28488435]
[25]
Guida, A.; Lhouty, M.H.; Tichit, D.; Figueras, F.; Geneste, P. Hydrotalcites as base catalysts. Kinetics of Claisen-Schmidt condensation, intramolecular condensation of acetonylacetone and synthesis of chalcone. Appl. Catal. A, 1997, 164, 251-264.
[http://dx.doi.org/10.1016/S0926-860X(97)00175-0]
[26]
Eddarir, S.; Cotelle, N.; Bakkour, Y.; Rolando, C. An efficient synthesis of chalcones based on the Suzuki reaction. Tetrahedron Lett., 2003, 44, 5359-5363.
[http://dx.doi.org/10.1016/S0040-4039(03)01140-7]
[27]
Anto, R.J.; Sukumaran, K.; Kuttan, G.; Rao, M.N.A.; Subbaraju, V.; Kuttan, R. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett., 1995, 97(1), 33-37.
[http://dx.doi.org/10.1016/0304-3835(95)03945-S] [PMID: 7585475]
[28]
Sharma, U.K.; Mohanakrishnan, D.; Sharma, N.; Equbal, D.; Sahal, D.; Sinha, A.K. Facile synthesis of vanillin-based novel bischalcones identifies one that induces apoptosis and displays synergy with Artemisinin in killing chloroquine resistant Plasmodium falciparum. Eur. J. Med. Chem., 2018, 155, 623-638.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.025] [PMID: 29929118]
[29]
Ur Rashid, H.; Xu, Y.; Ahmad, N.; Muhammad, Y.; Wang, L. Promising anti-inflammatory effects of chalcones via inhibition of cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor κb activities. Bioorg. Chem., 2019, 87, 335-365.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.033] [PMID: 30921740]
[30]
Singh, P.; Anand, A.; Kumar, V. Recent developments in biological activities of chalcones: A mini review. Eur. J. Med. Chem., 2014, 85, 758-777.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.033] [PMID: 25137491]
[31]
Mahapatra, D.K.; Asati, V.; Bharti, S.K. Chalcones and their therapeutic targets for the management of diabetes: Structural and pharmacological perspectives. Eur. J. Med. Chem., 2015, 92, 839-865.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.051] [PMID: 25638569]
[32]
Sahu, N.K.; Balbhadra, S.S.; Choudhary, J.; Kohli, D.V. Exploring pharmacological significance of chalcone scaffold: A review. Curr. Med. Chem., 2012, 19(2), 209-225.
[http://dx.doi.org/10.2174/092986712803414132] [PMID: 22320299]
[33]
Santosh, L.; Gaonkar, U.N. Vignesh, Synthesis and pharmacological properties of chalcones: a review. Res. Chem. Intermed., 2017, 43, 6043-6077.
[http://dx.doi.org/10.1007/s11164-017-2977-5]
[34]
Tajudeen Bale, A.; Mohammed Khan, K.; Salar, U.; Chigurupati, S.; Fasina, T.; Ali, F. Kanwal; Wadood, A.; Taha, M.; Sekhar Nanda, S.; Ghufran, M.; Perveen, S. Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies. Bioorg. Chem., 2018, 79, 179-189.
[http://dx.doi.org/10.1016/j.bioorg.2018.05.003] [PMID: 29763804]
[35]
Lipinski, B. Pathophysiology of oxidative stress in diabetes mellitus. J. Diabetes Complications, 2001, 15(4), 203-210.
[http://dx.doi.org/10.1016/S1056-8727(01)00143-X] [PMID: 11457673]
[36]
Khan, A.N.; Khan, R.A.; Ahmad, M.; Mushtaq, N. Role of antioxidant in oxidative stress and diabetes mellitus. J. Pharmacogn. Phytochem., 2015, 3, 217-220.
[37]
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]
[38]
Kayama, Y.; Raaz, U.; Jagger, A.; Adam, M.; Schellinger, I.N.; Sakamoto, M.; Suzuki, H.; Toyama, K.; Spin, J.M.; Tsao, P.S. Diabetic cardiovascular disease induced by oxidative stress. Int. J. Mol. Sci., 2015, 16(10), 25234-25263.
[http://dx.doi.org/10.3390/ijms161025234] [PMID: 26512646]
[39]
Bashary, R.; Khatik, G.L. Design, and facile synthesis of 1,3 diaryl-3-(arylamino)propan-1-one derivatives as the potential α-amylase inhibitors and antioxidants. Bioorg. Chem., 2019, 82, 156-162.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.010] [PMID: 30321778]
[40]
Olszowy, M.; Dawidowicz, A.L. Is it possible to use the DPPH and ABTS methods for reliable estimation of antioxidant power of colored compounds? Chem. Pap., 2018, 72, 393-400.
[http://dx.doi.org/10.1007/s11696-017-0288-3]
[41]
Salar, U.; Khan, K.M.; Chigurupati, S.; Taha, M.; Wadood, A.; Vijayabalan, S.; Ghufran, M.; Perveen, S. New hybrid hydrazinyl thiazole substituted chromones: As potential α-amylase inhibitors and radical (DPPH & ABTS) scavengers. Sci. Rep., 2017, 7(1), 16980.
[http://dx.doi.org/10.1038/s41598-017-17261-w] [PMID: 29209017]
[42]
Salar, U.; Khan, K.M.; Chigurupati, S.; Syed, S.; Vijayabalan, S.; Wadood, A.; Riaz, M.; Ghufran, M.; Perveen, S. New hybrid scaffolds based on hydrazinyl thiazole substituted coumarin; as novel leads of dual potential; In vitro α-amylase inhibitory and antioxidant (DPPH and ABTS radical scavenging) activities. Med. Chem., 2019, 15(1), 87-101.
[http://dx.doi.org/10.2174/1573406414666180903162243] [PMID: 30179139]
[43]
Rafique, R.; Khan, K.M. Arshia; Chigurupati, S.; Wadood, A.; Rehman, A.U.; Salar, U.; Venugopal, V.; Shamim, S.; Taha, M.; Perveen, S. Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles. Bioorg. Chem., 2020, 94103410
[http://dx.doi.org/10.1016/j.bioorg.2019.103410] [PMID: 31732193]
[44]
Salar, U.; Khan, K.M.; Jabeen, A.; Hussain, S.; Faheem, A.; Naqvi, F.; Perveen, S. Diversified thiazole substituted coumarins and chromones; As non-cytotoxic ROS and NO inhibitors. Lett. Drug Des. Discov., 2020, 17, 545-553.
[http://dx.doi.org/10.2174/1570180816666190611155218]
[45]
Khan, K.M.; Rahim, F.; Khan, A.; Ali, S.; Taha, M.; Saad, S.M.; Khan, M. Najeebullah; Shaikh, A.; Perveen, S.; Choudhary, M. I. Synthesis of benzophenone hydrazone analogs and their DPPH radical scavenging and urease inhibitory activities. J. Chem. Soc. Pak., 2015, 37, 479-483.
[46]
Khan, K.M.; Taha, M.; Naz, F.; Siddiqui, S.; Ali, S.; Rahim, F.; Perveen, S.; Choudhary, M.I. Acylhydrazide Schiff bases: DPPH radical and superoxide anion scavengers. Med. Chem., 2012, 8(4), 705-710.
[http://dx.doi.org/10.2174/157340612801216111] [PMID: 22571188]
[47]
Khan, K.M.; Shah, Z.; Ahmad, V.U.; Khan, M.; Taha, M.; Rahim, F.; Ali, S.; Ambreen, N.; Perveen, S.; Choudhary, M.I.; Voelter, W. 2,4,6-Trichlorophenylhydrazine Schiff bases as DPPH radical and super oxide anion scavengers. Med. Chem., 2012, 8(3), 452-461.
[http://dx.doi.org/10.2174/1573406411208030452] [PMID: 22530900]