The Influence of Halogens(CL) at Meta-positions of Aromatic Rings InChalcones on Their In Vitro Anti-inflammatory Activity
DOI:
https://doi.org/10.54361/Keywords:
Chalcones, m-chlorobenzaldehyde, m-chloroacetophenone, Ethyl alcohol, Anti-inflammatory activity, RAW 264.7 cellsAbstract
The discovery of new therapeutic agents for inflammatory disorders has attracted more attention in recent years. Chalcone term is given to the flavonoid compounds bearing the 1,3-diphenyl-2-propen-1-one framework. Generally, chalcones are precursors of flavonoids with two aromatic rings joined together through three carbons, Į, ȕ-unsaturated carbonyl system. In plants, chalcones are converted to the respective (2S)-flavanones by enzymatic reaction of chalcone isomerase. Based on the close chemical and biogenetic relationship between flavanones and chalcones, they are considered as natural products. For anti-inflammatory activity of chalcones, activated macrophages play an important role and compounds with that inhibit nitro oxide production by macrophages have been found potential for the prevention and treatment of inflammatory disorders. Some functional groups such as dimethylamine, methoxy and butoxy groups increase the electron density of the B-ringresulting in significant loss of anti-inflammatory activity. Therefore, in this project three compounds were synthesised for chalcones containing halogens (-Cl) at meta- positions on aromatic rings in chalcones and tested for their anti-inflammatory activity. The synthesized compounds were purified by column chromatography and characterised by 1H-NMR, 13C-NMR, FTIR, Mass and UV spectra. Further evaluation of theirin vitro anti-inflammatory activity were carried out using RAW 264.7 mouse macrophages. The test dose of chalcones were determined was cytotoxicity (MTT) assay on RAW264.7 mouse macrophages. The results showed that the halogen substitution at meta-positions on aromatic rings improved the anti-inflammatory activity for the compound (E)-1,3-bis(3-chlorophenyl) prop-2-en-1-one (III) shows the best activity.
References
Khatib S, Nerya O, Musa R, Shmuel M, Tamir S, Vaya J. Chalcones as potent tyrosinase inhibitors: the importance of a 2, 4-substituted resorcinol moiety. Bioorganic & Medicinal Chemistry. 2005;13(2): 433-41.
Nowakowska Z. A review of anti-infective and anti-inflammatory chalcones. European Journal of Medicinal Chemistry. 2007; 42(2):125-37.
Go M, Wu X, Liu X. Chalcones: an update on cytotoxic and chemoprotective properties. Current medicinal chemistry. 2005;12(4): 483-99.
Syam S, Abdelwahab SI, Al-Mamary MA, Mohan S. Synthesis of chalcones with anticancer activities. Molecules. 2012;17(6):6179-95.
Ducki S. The development of chalcones as promising anticancer agents. Drugs. 2007;10(1):
Tatsuzaki J, Bastow KF, Nakagawa-Goto K, Nakamura S, Itokawa H, Lee K-H. Dehydrozingerone, Chalcone, and Isoeugenol Analogues as in Vitro Anticancer Agents#. Journal of Natural Products. 2006; 69(10): 1445-9.
Boumendjel A, Ronot X, Boutonnat J. Chalcones derivatives acting as cell cycle blockers: potential anti cancer drugs? Current Drug Targets. 2009;10(4): 363-71.
Sashidhara KV, Kumar A, Kumar M, Sarkar J, Sinha S. Synthesis and in vitro evaluation of novel coumarin–chalcone hybrids as potential anticancer agents. Bioorganic &Medicinal Chemistry Letters. 2010; 20(24): 7205-11.
Bandgar BP, Gawande SS, Bodade RG, Gawande NM, Khobragade CN. Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti- inflammatory, antioxidant and antimicrobial agents. Bioorganic & Medicinal Chemistry. 2009; 17(24): 8168-73.
Bandgar BP, Gawande SS, Bodade RG, Totre JV, Khobragade CN. Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, anti- inflammatory and antioxidant agents. Bioorganic & Medicinal Chemistry. 2010; 18(3): 1364-70.
Hsieh H-K, Lee T-H, Wang J-P, Wang J-J, Lin C-N. Synthesis and anti- inflammatory effect of chalcones and related compounds. Pharmaceutical research. 1998;15(1):39-46.
Hsieh H-K, Tsolt, Wang JP, Lin Cn. Synthesis and Anti inflammatory Effect of Chalcones. Journal of Pharmacy and Pharmacology. 2000; 52(2): 163-71.
Liaras K, Geronikaki A, Glamoþlija J, ûiriü A, Sokoviü M. Thiazole-based chalcones as potent antimicrobial agents. Synthesis and biological evaluation. Bioorganic & Medicinal Chemistry. 2011;19(10):3135-40.
Solankee A, Kapadia K, ûiriü A, Sokoviü M, Doytchinova I, Geronikaki A. Synthesis of some new S-triazine based chalcones and their derivatives as potent antimicrobial agents. European Journal of Medicinal Chemistry. 2010; 45(2): 510-8.
Siddiqui ZN, Musthafa TM, Ahmad A, Khan AU. Thermal solvent-free synthesis of novel pyrazolyl chalcones and pyrazolines as potential antimicrobial agents. Bioorganic & Medicinal Chemistry Letters. 2011; 21(10): 2860-5.
Choudhary AN, Juyal V. Synthesis of chalcone and their derivatives as antimicrobial agents. Int Pharmaceut Sci. 2011; 3:125-8.
Selway JT. Antiviral activity of flavones and flavans. Progress in Clinical and Biological Research. 1986; 213: 521.
El-Subbagh HI, Abu-Zaid SM, Mahran MA, Badria FA, Al-Obaid AM. Synthesis and biological evaluation of certain Į, ȕ-unsaturated ketones and their corresponding fused pyridines as antiviral and cytotoxic agents. Journal of Medicinal Chemistry. 2000; 43(15): 2915-21.
Binder D, Noe C, Holzer W, Rosenwirth B. Thiophene as a structural element of physiologically active substances. 12. Thiophene analogs of antiviral chalcones. Archiv der Pharmazie. 1985;318(1):49.
Tadigoppula N, Korthikunta V, Gupta S, Kancharla P, Khaliq T, Soni A, et al. Synthesis and insight into the structure–activity relationships of chalcones as antimalarial agents. Journal of Medicinal Chemistry. 2012; 56(1): 31-45.
Ferrer R, Lobo G, Gamboa N, Rodrigues J, Abramjuk C, Jung K, et al. Synthesis of [(7-chloroquinolin-4-yl) amino] chalcones: potential antimalarial and anticancer agents. Scientia Pharmaceutica. 2009; 77(4): 725-42.
Ohnogi H, Sugiyama K, Enoki T, Kobayashi E, Sagawa H, Kato I. Chalcone Compounds. Google Patents; 2009.
Visavadiya NP, Narasimhacharya A. Ameliorative effects of herbal combinations in hyperlipidemia. Oxidative Medicine and Cellular Longevity. 2011; 2011.
Raj CGD, Sarojini BK, Bhanuprakash V, Yogisharadhya R, Swamy BEK, Raghavendra R. Studies on radioprotective and antiviral activities of some bischalcone derivatives. Medicinal Chemistry Research. 2012;21(9):2671-9.
Wilson C. Synthesis and Characterisation of Chalcones. J Asian Med chem. 1938;61:2303.
Claisen L, Claparede A. Ber., 1881, 14, 2463; b) Claisen L. Ber; 1887.
Datta S, Murtiv, Seshadri T. Syenthesis of 2'-Methoxyflavanones. Natl Inst Science Commumnation Dr Ks Krishnan Marg,New Delhi 110 012, INDIA; 1971. p. 614-&.
Makrandi J, Kumar S. An Efficient Synthesis of 2'-Hydroxychalcones. Asian Journal of 2004;16(2):1189.
Lin W-W, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. The Journal of Clinical Investigation. 2007; 117(5): 1175-83.
Rojas J, Payá M, Dominguez JN, Ferrandiz ML. The synthesis and effect of fluorinated chalcone derivatives on nitric oxide production. Bioorganic & MedicinalChemistry Letters. 2002; 12(15): 1951-4.
Ferrero Miliani L, Nielsen O, Andersen P, Girardin S. Chronic inflammation: importance of NOD2 and NALP3 in interleukin ȕ generation. Clinical & Experimental Immunology. 2007; 147(2): 227-35.
Ortolan XR, Fenner BP, Mezadri TJ, Tames DR, Corrêa R, de Campos Buzzi F. Osteogenic potential of a chalcone in a critical-size defect in rat calvaria bone. Journal of Cranio-Maxillofacial Surgery. 2014; 42(5): 520-4.
Sharma J, Al-Omran A, Parvathy S. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15(6):252-9.
Laveti D, Kumar M, Hemalatha R, Sistla R, GM Naidu V, Talla V, et al. Anti- inflammatory treatments for chronic diseases: a review. Inflammation & Allergy- Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2013;12(5):349-61.
Deshpande AM, Argade NP, Natu AA, Eckman J. Synthesis and Screening of a Combinatorial Library of Naphthalene Substituted Chalcones: Inhibitors of Leukotriene B 4. Bioorganic & Medicinal Chemistry. 1999; 7(6): 1237-40.
Perozo-Rondón E, Martín-Aranda RM, Casal B, Durán-Valle CJ, Lau WN, Zhang X, et al. Sonocatalysis in solvent free conditions: An efficient eco-friendly methodology to prepare chalcones using a new type of amino Grafted Zeolites. Catalysis today. 2006; 114(2): 183-7.
Bohm BA. Introduction to flavonoids: Harwood Academic Publishers; 1998.
Chopra PG. Chalcones: A brief review. International Journal of Research in Engineering and Applied Sciences. 2016; 6(5): 173-85.
Narender T, Reddy KP. A simple and highly efficient method for the synthesis of chalcones by using borontrifluoride-etherate. Tetrahedron Letters. 2007; 48(18): 3177-80.
Jayapal M, Sreedhar N. Anhydrous K2CO3 as Catalyst for the Synthesis of Chalcones under Microwave Irradiation. 2010.
Jayapal M, Sreedhar N. Synthesis and characterization of 4-hydroxy chalcones by Aldol condensation using SOCl2/EtOH. Int J Curr Pharm Res. 2010;2(4):60-2.
Brun E, Safer A, Carreaux F, Bourahla K, L'Helgoua'Ch J-M, Bazureau J-P, et al. Microwave-Assisted Condensation Reactions of Acetophenone Derivatives and Activated Methylene Compounds with Aldehydes Catalyzed by Boric Acid under Solvent-Free Conditions. Molecules. 2015; 20(6): 11617-31.
Rao YK, Fang S-H, Tzeng Y-M. Synthesis and biological evaluation of 3ƍ, 4ƍ, 5ƍ- trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation. Bioorganic & medicinal chemistry. 2009;17(23):7909-14.
Rahman MA. Chalcone: A valuable insight into the recent advances and potential pharmacological activities. Chemical Sciences Journal. 2011.
Aoki N, Muko M, Ohta E, Ohta S. C-geranylated chalcones from the stems of Angelica keiskei with superoxide-scavenging activity. Journal of Natural Products. 2008; 71(7): 1308-10.
Modzelewska A, Pettit C, Achanta G, Davidson NE, Huang P, Khan SR. Anticancer activities of novel chalcone and bis-chalcone derivatives. Bioorganic & Medicinal Chemistry. 2006; 14(10): 3491-5.
Boumendjel A, Boccard J, Carrupt P-A, Nicolle E, Blanc M, Geze A, et al. Antimitotic and antiproliferative activities of chalcones: forward structure– activity relationship. Journal of Medicinal Chemistry. 2008; 51(7): 2307-10.
Vogel S, Heilmann Jr. Synthesis, cytotoxicity, and antioxidative activity of minor prenylated chalcones from Humulus lupulus. Journal of Natural Products. 2008; 71(7): 1237-41.
Enoki T, Ohnogi H, Nagamine K, Kudo Y, Sugiyama K, Tanabe M, et al. Antidiabetic activities of chalcones isolated from a Japanese herb, Angelica keiskei. Journal ofAgricultural and Food Chemistry. 2007; 55(15): 6013-7.
Bashir R, Ovais S, Yaseen S, Hamid H, Alam M, Samim M, et al. Synthesis of some new 1, 3, 5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents. Bioorganic & Medicinal Chemistry letters. 2011; 21(14): 4301-5. 6(15): 7167-76.
Lorenzo P, Alvarez R, Ortiz MA, Alvarez S, Piedrafita FJ, de Lera AnR. Inhibition of IțB kinase-ȕ and anticancer activities of novel chalcone adamantyl arotinoids. Journal of Medicinal Chemistry. 2008; 51(17): 5431-40.
Nowakowska Z, KĊdzia B, Schroeder G. Synthesis, physicochemical properties and antimicrobial evaluation of new (E)-chalcones. European journal of Medicinal Chemistry. 2008; 43(4): 707-13.
Sivakumar PM, Ganesan S, Veluchamy P, Doble M. Novel chalcones and 1, 3, triphenyl pyrazoline derivatives as antibacterial agents. ChemicalBiology & Drug Design. 2010; 76(5): 407-11.
Kumar D, Kumar NM, Akamatsu K, Kusaka E, Harada H, Ito T. Synthesis and biological evaluation of indolyl chalcones as antitumor agents. Bioorganic & Medicinal Chemistry letters. 2010; 20(13): 3916-9.
Mahapatra DK, Bharti SK. Therapeutic potential of chalcones as cardiovascular agents. Life Sciences. 2016; 148: 154-72.
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Copyright (c) 2018 Osama H O Almajdoub, Mallikarjuna Rao Pichika , Dr. Ramu Meesalsa (Author)
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