Generic placeholder image

Current Chemical Biology

Editor-in-Chief

ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Research Article

Synthesis and Antibacterial Activity of New Chalcones Bearing an Imidazo[ 1,2-a]pyridine Moiety

Author(s): Siavash Salek Soltani, S. Morteza F. Farnia* and Alireza Foroumadi*

Volume 15, Issue 2, 2021

Published on: 23 February, 2021

Page: [163 - 170] Pages: 8

DOI: 10.2174/2212796815666210223110208

Price: $65

Abstract

Aim and Objective: Herein, A series of new imidazo[1,2-a]pyridine-chalcone derivatives 3a-m were designed and synthesized to find a new class of antibacterial agents. These compounds were prepared by the aldol condensation of 2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde 2a-b with acetophenone derivatives and other aromatic acetyls. High reaction yields were obtained in a short reaction time, through applying this multi-step pathway.

Materials and Methods: In vitro antibacterial activities of the synthesized imidazo[1,2-a]pyridinechalcones were measured against S. aureus, B. subtilis and E. coli with MIC values of 32 -128 μg/mL. Finally, essential structural analyses such as CHN and NMR spectroscopies were used to identify the synthesized chalcones based on imidazo[1,2-a]pyridine derivatives.

Results: The results showed that most of the products presented moderate to good antibacterial activities. Compounds 3b, 3d, 3g, 3l and 3m revealed obvious potency against S. aureus, B. subtilis and E. coli with MIC values of 32 μg/mL and 64 μg/mL, which were better when compared with other chalcones.

Conclusion: The synthesized antibacterial compounds were obtained with appealing advantages such as high purity, simple pathway, good to excellent yields, inexpensive and easy availability of materials as well as good activities against bacteria. So in this work, a new class of antibacterial chalcones based on imidazo[1,2-a]pyridine has been reported.

Keywords: Imidazo[1, 2-a]pyridines, chalcones, antibacterial agent, biological activity, gram positive bacteria, gram negative bacteria.

Graphical Abstract
[1]
Enguehard-Gueiffier C, Gueiffier A. Recent progress in the pharmacology of imidazo[1,2-a]pyridines. Mini Rev Med Chem 2007; 7(9): 888-99.
[http://dx.doi.org/10.2174/138955707781662645] [PMID: 17897079]
[2]
Bagdi AK, Santra S, Monir K, Hajra A. Synthesis of imidazo[1,2-a]pyridines: a decade update. Chem Commun (Camb) 2015; 51(9): 1555-75.
[http://dx.doi.org/10.1039/C4CC08495K] [PMID: 25407981]
[3]
Rival Y, Grassy G, Michel G. Synthesis and antibacterial activity of some imidazo[1,2-a]pyrimidine derivatives. Chem Pharm Bull (Tokyo) 1992; 40(5): 1170-6.
[http://dx.doi.org/10.1248/cpb.40.1170] [PMID: 1394630]
[4]
Tashrifi Z, Mohammadi-Khanaposhtani M, Larijani B, et al. C3-Functionalization of imidazo[1,2-a]pyridines. Eur J Org Chem 2020; 2020: 269-84.
[http://dx.doi.org/10.1002/ejoc.201901491]
[5]
Rival Y, Grassy G, Taudou A, et al. Antifungal activity in vitro of some imidazo[1,2-a]pyrimidine derivatives. Eur J Med Chem 1991; 26: 13-8.
[http://dx.doi.org/10.1016/0223-5234(91)90208-5]
[6]
Hamdouchi C, de Blas J, del Prado M, Gruber J, Heinz BA, Vance L. 2-Amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]imid azo[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: stereospecific synthesis and antiviral activity. J Med Chem 1999; 42(1): 50-9.
[http://dx.doi.org/10.1021/jm9810405] [PMID: 9888832]
[7]
Arbabi HA, Salek Soltani S, Salehi H, et al. Convenient synthesis of heterocyclic azo dyes in the class of pyranopyrazoles and chromenes. J Chem Res 2018; 42: 68-72.
[http://dx.doi.org/10.3184/174751918X15177611816526]
[8]
Rupert KC, Henry JR, Dodd JH, et al. Imidazopyrimidines, potent inhibitors of p38 MAP kinase. Bioorg Med Chem Lett 2003; 13(3): 347-50.
[http://dx.doi.org/10.1016/S0960-894X(02)01020-X] [PMID: 12565927]
[9]
Salek Soltani S, Farnia SMF, Foroumadi A. A comparison between Suzuki cross-coupling reaction and direct arylation in the synthesis of new antibacterial imidazo-pyrazines/pyridazines. J Heterocycl Chem 2020; 57: 1770-80.
[http://dx.doi.org/10.1002/jhet.3902]
[10]
Badaway E, Kappe T. Benzimidazole condensed ring system. IX. Potential antineoplastics. new synthesis of some pyrido[1,2-α]benzimidazoles and related derivative. Eur J Med Chem 1995; 30: 327-32.
[http://dx.doi.org/10.1016/0223-5234(96)88241-9]
[11]
Hranjec M, Kralj M, Piantanida I, et al. Novel cyano- and amidino-substituted derivatives of styryl-2-benzimidazoles and benzimidazo[1,2-a]quinolines. Synthesis, photochemical synthesis, DNA binding, and antitumor evaluation, part 3. J Med Chem 2007; 50(23): 5696-711.
[http://dx.doi.org/10.1021/jm070876h] [PMID: 17935309]
[12]
Kotovskaya SK, Baskakova ZM, Charushin VN, et al. Synthesis and antiviral activity of fluorinated pyrido[1,2-a]benzimidazoles. Pharm Chem J 2005; 39: 574-8.
[http://dx.doi.org/10.1007/s11094-006-0023-9]
[13]
Lhassani M, Chavignon O, Chezal JM, et al. Synthesis and antiviral activity of imidazo[1,2-a]pyridines. Eur J Med Chem 1999; 34: 271-4.
[http://dx.doi.org/10.1016/S0223-5234(99)80061-0]
[14]
Humphries AC, Gancia E, Gilligan MT, et al. 8-Fluoroimidazo[1,2-a]pyridine: synthesis, physicochemical properties and evaluation as a bioisosteric replacement for imidazo[1,2-a]pyrimidine in an allosteric modulator ligand of the GABA A receptor. Bioorg Med Chem Lett 2006; 16(6): 1518-22.
[http://dx.doi.org/10.1016/j.bmcl.2005.12.037] [PMID: 16386901]
[15]
Fuchs K, Romig M, Mendla K, Briem H, Fechteler K. Novel beta-amyloid inhibitors, method for producing the same and the use thereof as medicaments. Patent WO 2002014313, 2002.
[16]
Davey D, Erhardt PW, Lumma WC Jr, et al. Cardiotonic agents. 1. Novel 8-aryl-substituted imidazo[1,2-a]- and -[1,5-a]pyridines and imidazo[1,5-a]pyridinones as potential positive inotropic agents. J Med Chem 1987; 30(8): 1337-42.
[http://dx.doi.org/10.1021/jm00391a012] [PMID: 3039131]
[17]
Fookes CJR, Pham TQ, Mattner F, et al. Synthesis and biological evaluation of substituted [18F]imidazo[1,2-a]pyridines and [18F]pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography. J Med Chem 2008; 51(13): 3700-12.
[http://dx.doi.org/10.1021/jm7014556] [PMID: 18557607]
[18]
Mizushige K, Ueda T, Yukiiri K, Suzuki H. Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc Drug Rev 2002; 20(3): 163-74.
[http://dx.doi.org/10.1111/j.1527-3466.2002.tb00085.x] [PMID: 12397365]
[19]
Almirante L, Polo L, Mugnaini A, et al. Derivatives of imidazole. I. synthesis and reactions of imidazo[1,2-α]pyridines with analgesic, antiinflammatory, antipyretic, and anticonvulsant activity. J Med Chem 1965; 8: 305-12.
[http://dx.doi.org/10.1021/jm00327a007] [PMID: 14329509]
[20]
Boerner RJ, Moller HJ. Saripidem - a new treatment for panic disorders. Psychopharmakother 1997; 4: 145-8.
[21]
Gudmundsson K, Boggs SD. Chemical compounds. Patent WO 2006026703, 2006.
[22]
Bandgar BP, Patil SA, Gacche RN, et al. Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett 2010; 20(2): 730-3.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.068] [PMID: 20005707]
[23]
Ni LM, Meng CQ, Sikorski JA. Recent advances in therapeutic chalcones. Expert Opin Ther Pat 2004; 14: 1669-91.
[http://dx.doi.org/10.1517/13543776.14.12.1669]
[24]
Zhu XF, Xie BF, Zhou JM, et al. Blockade of vascular endothelial growth factor receptor signal pathway and antitumor activity of ON-III (2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone), a component from Chinese herbal medicine. Mol Pharmacol 2005; 67(5): 1444-50.
[http://dx.doi.org/10.1124/mol.104.009894] [PMID: 15703376]
[25]
Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Liljefors T. Antileishmanial chalcones: statistical design, synthesis, and three-dimensional quantitative structure-activity relationship analysis. J Med Chem 1998; 41(24): 4819-32.
[http://dx.doi.org/10.1021/jm980410m] [PMID: 9822551]
[26]
Dimmock JR, Kandepu NM, Hetherington M, et al. Cytotoxic activities of Mannich bases of chalcones and related compounds. J Med Chem 1998; 41(7): 1014-26.
[http://dx.doi.org/10.1021/jm970432t] [PMID: 9544201]
[27]
Sabzevari O, Galati G, Moridani MY, Siraki A, O’Brien PJ. Molecular cytotoxic mechanisms of anticancer hydroxychalcones. Chem Biol Interact 2004; 148(1-2): 57-67.
[http://dx.doi.org/10.1016/j.cbi.2004.04.004] [PMID: 15223357]
[28]
Lin YM, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen FC. Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem 2002; 10(8): 2795-802.
[http://dx.doi.org/10.1016/S0968-0896(02)00094-9] [PMID: 12057669]
[29]
Liu M, Wilairat P, Go ML. Antimalarial alkoxylated and hydroxylated chalcones [corrected]: structure-activity relationship analysis. J Med Chem 2001; 44(25): 4443-52.
[http://dx.doi.org/10.1021/jm0101747] [PMID: 11728189]
[30]
Madan B, Batra S, Ghosh B. 2′-hydroxychalcone inhibits nuclear factor-kappaB and blocks tumor necrosis factor-α- and lipopolysaccharide-induced adhesion of neutrophils to human umbilical vein endothelial cells. Mol Pharmacol 2000; 58(3): 526-34.
[http://dx.doi.org/10.1124/mol.58.3.526] [PMID: 10953045]
[31]
Sivakumar PM, Iyer G, Natesan L, et al. 3′-Hydroxy-4-methoxychalcone as a potential antibacterial coating on polymeric biomaterials. Appl Surf Sci 2010; 256: 6018-24.
[http://dx.doi.org/10.1016/j.apsusc.2010.03.112]
[32]
Sivakumar PM, Priya S, Doble M. Synthesis, biological evaluation, mechanism of action and quantitative structure-activity relationship studies of chalcones as antibacterial agents. Chem Biol Drug Des 2009; 73(4): 403-15.
[http://dx.doi.org/10.1111/j.1747-0285.2009.00793.x] [PMID: 19291103]
[33]
Rajitha G, Ravibabu V, Ramesh G, et al. Synthesis and antimicrobial activity of novel imidazo[1,2-a]pyridinopyrimidine-2,4,6(1H,3H,5H)-triones and thioxopyrimidine-4,6(1H,5H)diones. Res Chem Intermed 2016; 42: 1989-98.
[http://dx.doi.org/10.1007/s11164-015-2130-2]
[34]
Maleki A, Taheri-Ledari R, Rahimi J, Soroushnejad M, Hajizadeh Z. Facile peptide bond formation: effective interplay between isothiazolone rings and silanol groups at silver/iron oxide nanocomposite surfaces. ACS Omega 2019; 4(6): 10629-39.
[http://dx.doi.org/10.1021/acsomega.9b00986] [PMID: 31460161]
[35]
Rajitha G, Ravibabu V, Ramesh G, Rajitha B. Synthesis and antimicrobial activity of novel imidazo[1,2-a]pyridinopyrimidine-2,4,6(1H,3H,5H)- triones and thioxopyrimidine-4,6(1H,5H)diones. Res Chem Intermed 2016; 42: 1989-98.
[http://dx.doi.org/10.1007/s11164-015-2130-2]
[36]
Palombo EA, Semple SJ. Antibacterial activity of traditional Australian medicinal plants. J Ethnopharmacol 2001; 77(2-3): 151-7.
[http://dx.doi.org/10.1016/S0378-8741(01)00290-2] [PMID: 11535358]
[37]
Yang MX, Lin X, Yu P, et al. Syntheses, structures and antibacterial activities of two nickel(II) complexes with N‐hexanoylsalicylhydrazide ligand. Chin J Chem 2005; 23: 1407-11.
[http://dx.doi.org/10.1002/cjoc.200591407]
[38]
NCCLS. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically M7-A5 Wayne: National Committee on Clinical Laboratory Standards . 2000; Vol. 20: p. 2.
[39]
Qi Y, Jiao B, Ma X, Cui W, Ma S. Synthesis and antibacterial activity of novel 4′'-O-carbamoyl erythromycin-A derivatives. Arch Pharm (Weinheim) 2010; 343(8): 458-64.
[http://dx.doi.org/10.1002/ardp.200900288] [PMID: 20803622]
[40]
Fisher MH, Lusi A. Imidazo(1,2-a)pyridine anthelmintic and antifungal agents. J Med Chem 1972; 15(9): 982-5.
[http://dx.doi.org/10.1021/jm00279a026] [PMID: 5065787]
[41]
Sayeed IB, Lakshma Nayak V, Shareef MA, Chouhan NK, Kamal A. Design, synthesis and biological evaluation of imidazopyridine-propenone conjugates as potent tubulin inhibitors. MedChemComm 2017; 8(5): 1000-6.
[http://dx.doi.org/10.1039/C7MD00043J] [PMID: 30108815]
[42]
Kishore BN, Unyala R, Begum A, et al. Synthesis characterization of some novel pyrazoline incorporated imidazo[1,2-a]pyridines for anti-inflammatory and anti-bacterial activities. Pharma Chem 2017; 9: 45-9.
[43]
Schaenzer AJ, Wlodarchak N, Drewry DH, et al. A screen for kinase inhibitors identifies antimicrobial imidazopyridine aminofurazans as specific inhibitors of the Listeria monocytogenes PASTA kinase PrkA. J Biol Chem 2017; 292(41): 17037-45.
[http://dx.doi.org/10.1074/jbc.M117.808600] [PMID: 28821610]
[44]
Huang WC, Lee CH, Liu JW. Clinical characteristics and risk factors for mortality in patients with meningitis caused by Staphylococcus aureus and vancomycin minimal inhibitory concentrations against these isolates. J Microbiol Immunol Infect 2010; 43(6): 470-7.
[http://dx.doi.org/10.1016/S1684-1182(10)60073-4] [PMID: 21195973]
[45]
Zhao PL, Liu CL, Huang W, Wang YZ, Yang GF. Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues. J Agric Food Chem 2007; 55(14): 5697-700.
[http://dx.doi.org/10.1021/jf071064x] [PMID: 17579441]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy