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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Design, Synthesis, Docking and Biological Evaluation of Novel 4-hydroxy Coumarin Derivatives

Author(s): N. Ramalakshmi, S.R. Chitra*, P. Manimegalai and S. Arunkumar

Volume 17, Issue 2, 2021

Published on: 31 January, 2020

Page: [201 - 213] Pages: 13

DOI: 10.2174/1573409916666200131142619

Price: $65

Abstract

Background: Hospital-acquired (HA) infections are caused due to E. coli, which is resistant to multiple drugs particularly to fluoroquinolone class of drugs. Urinary tract infections (UTI) affects people in the community and hospitals. 150 million people per annum are suffering from UTI worldwide.

Methods: In this present study, we designed 36 novel coumarin derivatives, also we predicted pharmacokinetic and toxicity parameters. Docking studies were also carried out and all the compounds were evaluated for antibacterial activity against resistant quinolone E. coli strain ATCC 25922. It was interesting to note that the introduction of electron-withdrawing group on the aromatic ring resulted in compounds with an increased antibacterial activity, which is observed in compound 6 (with 4-nitro substitution), compound 23 (chloro) and compound 30 (chloro, nitro).

Results: From the MIC results, it was observed that compounds 6, 23 and 30 showed higher activity with 0.5μg/ml, 0. 12 μg/ml, 0.5 μg/ml respectively. Docking studies were performed with the active site of DNA gyrase (PDB ID: 4CKK). The maximum binding energy was found to be -10.7 Kcal/mol.

Conclusion: From the study, it was found that 3 compounds were potentially active against quinolone- resistant E. coli strains. This study can further be extended for in vivo evaluation.

Keywords: E. coli strains, coumarin derivatives, evaluation of novel 4-hydroxy, MIC results, DNA gyrase, toxicity parameters.

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[1]
Dalhoff, A. Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdiscip. Perspect. Infect. Dis., 2012, 2012, 976273.
[http://dx.doi.org/10.1155/2012/976273] [PMID: 23097666]
[2]
Rath, S.; Padhy, R.N. Prevalence of fluoroquinolone resistance in Escherichia coli in an Indian teaching hospital and adjoining communities. J. Taibah Uni. Med. Sci., 2015, 10(4), 504-508.
[http://dx.doi.org/10.1016/j.jtumed.2015.02.009]
[3]
Fasugba, O.; Gardner, A.; Mitchell, B.G.; Mnatzaganian, G. Ciprofloxacin resistance in community- and hospital-acquired Escherichia coli urinary tract infections: a systematic review and meta-analysis of observational studies. BMC Infect. Dis., 2015, 15(1), 545.
[http://dx.doi.org/10.1186/s12879-015-1282-4] [PMID: 26607324]
[4]
WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR). Critically important antimicrobials for human medicine 3rd Revision 2011. WHO Document Production Services, Geneva, Switzerland. Clin. Infect. Dis., 2012, 55, 712-719.
[5]
Zurfluh, K.; Abgottspon, H.; Hächler, H.; Nüesch-Inderbinen, M.; Stephan, R. Quinolone resistance mechanisms among extended-spectrum beta-lactamase (ESBL) producing Escherichia coli isolated from rivers and lakes in Switzerland. PLoS One, 2014, 9(4), e95864.
[http://dx.doi.org/10.1371/journal.pone.0095864] [PMID: 24755830]
[6]
Jain, P.K.; Joshi, H. Coumarin: chemical and pharmacological profile. J. Appl. Pharm. Sci., 2012, 2(6), 236-240.
[7]
Bouasla, S.; Amaro-Gahete, J.; Esquivel, D.; López, M.I.; Jiménez-Sanchidrián, C.; Teguiche, M.; Romero-Salguero, F.J. Coumarin derivatives solvent-free synthesis under microwave irradiation over heterogeneous solid catalysts. Molecules, 2017, 22(12), 2072.
[http://dx.doi.org/10.3390/molecules22122072] [PMID: 29182553]
[8]
Anand, P.; Singh, B.; Singh, N. A review on coumarins as acetylcholinesterase inhibitors for Alzheimer’s disease. Bioorg. Med. Chem., 2012, 20(3), 1175-1180.
[http://dx.doi.org/10.1016/j.bmc.2011.12.042] [PMID: 22257528]
[9]
Al-Amiery, A.A.; Al-Majedy, Y.K.; Kadhum, A.A.H.; Mohamad, A.B. Novel macromolecules derived from coumarin: synthesis and antioxidant activity. Sci. Rep., 2015, 5, 11825.
[http://dx.doi.org/10.1038/srep11825] [PMID: 26134661]
[10]
S. DarlinQuine. Synthesis, characterization, antibacterial evaluation and molecular docking studies of 2-azetidinone derivatives as novel DNA gyrase inhibitors. Int. Lett. Chem. Phys. Astro., 2015, 47, 94-108.
[11]
Reddy, D.R.; Namratha, R.J. Synthesis and biological evaluation of 6-fluoro benzothiazole substituted pyrazoloazetidinones. Der. PharmaChem., 2013, 5, 235-240.
[12]
Srinivas, S.; Aparna, V.; Rajkamal, B.; Saikiran, G. Synthesis and antimicrobial evaluation of some novel quinolone incorporated azetidinones. Thiazolidinones. JPSI, 2012, 1, 41-43.
[13]
Naik, P.J.; Parekh, D.V.; Desai, P.S. Synthesis and biological evaluation of azitidinone and their derivative as antimicrobial agents. Adv. Appl. Sci. Res., 2013, 4, 324-329.
[14]
O’Driscoll, M.; Greenhalgh, K.; Young, A.; Turos, E.; Dickey, S.; Lim, D.V. Studies on the antifungal properties of N-thiolated β-lactams. Bioorg. Med. Chem., 2008, 16(16), 7832-7837.
[http://dx.doi.org/10.1016/j.bmc.2008.06.035] [PMID: 18672374]
[15]
Thakur, P.K.; Kumar, J.; Ray, D.; Anjum, F.; Hassan, M.I. Search of potential inhibitor against New Delhi metallo-beta-lactamase 1 from a series of antibacterial natural compounds. J. Nat. Sci. Biol. Med., 2013, 4(1), 51-56.
[http://dx.doi.org/10.4103/0976-9668.107260] [PMID: 23633835]
[16]
Raj, R.; Biot, C.; Carrère-Kremer, S.; Kremer, L.; Guérardel, Y.; Gut, J.; Rosenthal, P.J.; Kumar, V. 4-Aminoquinoline-β-lactam conjugates: synthesis, antimalarial, and antitubercular evaluation. Chem. Biol. Drug Des., 2014, 83(2), 191-197.
[http://dx.doi.org/10.1111/cbdd.12225] [PMID: 24034147]
[17]
Reddy, P.A.; Hsiang, B.C.; Latifi, T.N.; Hill, M.W.; Woodward, K.E.; Rothman, S.M.; Ferrendelli, J.A.; Covey, D.F. 3,3-Dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones: a new class of anticonvulsant agents. J. Med. Chem., 1996, 39(9), 1898-1906.
[http://dx.doi.org/10.1021/jm9600196] [PMID: 8627613]
[18]
Alonso, E.; delPozo, C.; Gonzalez, J. Synthesis of α, α-disubstituted β-amino esters and peptide derivatives. Syn. Lett., 2002, 2002(01), 0069-0072.
[http://dx.doi.org/10.1055/s-2002-19326]
[19]
Srivastava, S.K.; Srivastava, S.; Srivastava, S.D. Synthesis of new carbazolyl-thiadiazol-2-oxo-azetidines: Antimicrobial, anticonvulsant and anti-inflammatory agents. Curr. Res. Bioorg. Org. Chem., 1999, 38B, 183-187.
[20]
Skiles, J.W.; McNeil, D. Spiro indolinone beta-lactams, inhibitors of poliovirus and rhinovlrus 3C-proteinases. Tetrahedron Lett., 1990, 31(50), 7277-7280.
[http://dx.doi.org/10.1016/S0040-4039(00)88543-3]
[21]
Vashi, B.S.; Mehta, D.S.; Shah, V.H. Synthesis and biological activity of 4‐Thiazolidinones, 2‐Azetidinones, 4‐Imidazolinone Derivatives Having Thymol Moiety. ChemInform, 1990, 26(47), 1995.
[http://dx.doi.org/10.1002/chin.199547230]
[22]
Wu, G.; Tormos, W. A catalytic asymmetric synthesis of a spirofusedazetidinone as a cholesterol absorption inhibitor. J. Org. Chem., 1997, 62(18), 6412-6414.
[http://dx.doi.org/10.1021/jo9704366]
[23]
Lagoja, I.M. Pyrimidine as constituent of natural biologically active compounds. Chem. Biodivers., 2005, 2(1), 1-50.
[http://dx.doi.org/10.1002/cbdv.200490173] [PMID: 17191918]
[24]
De Clercq, E.; Sakuma, T.; Baba, M.; Pauwels, R.; Balzarini, J.; Rosenberg, I.; Holý, A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res., 1987, 8(5-6), 261-272.
[http://dx.doi.org/10.1016/S0166-3542(87)80004-9] [PMID: 3451698]
[25]
Bekhit, A.A.; Fahmy, H.T.; Rostom, S.A.; Baraka, A.M. Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial Agents. Eur. J. Med. Chem., 2003, 38(1), 27-36.
[http://dx.doi.org/10.1016/S0223-5234(02)00009-0] [PMID: 12593914]
[26]
Virsodia, V.; Pissurlenkar, R.R.; Manvar, D.; Dholakia, C.; Adlakha, P.; Shah, A.; Coutinho, E.C. Synthesis, screening for antitubercular activity and 3D-QSAR studies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxamides. Eur. J. Med. Chem., 2008, 43(10), 2103-2115.
[http://dx.doi.org/10.1016/j.ejmech.2007.08.004] [PMID: 17950956]
[27]
Grivsky, E.M.; Lee, S.; Sigel, C.W.; Duch, D.S.; Nichol, C.A. Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine. J. Med. Chem., 1980, 23(3), 327-329.
[http://dx.doi.org/10.1021/jm00177a025] [PMID: 6928967]
[28]
Lin, T.S.; Mancini, W.R. Synthesis and antineoplastic activity of 3′-azido and 3′-amino analogues of pyrimidine deoxyribonucleoside. J. Med. Chem., 1983, 26(4), 544-548.
[http://dx.doi.org/10.1021/jm00358a016] [PMID: 6834387]
[29]
Falco, E.A.; Goodwin, L.G.; Hitchings, G.H.; Rollo, I.M.; Russell, P.B. 2:4-diaminopyrimidines- a new series of antimalarials. Br. J. Pharmacol. Chemother., 1951, 6(2), 185-200.
[http://dx.doi.org/10.1111/j.1476-5381.1951.tb00634.x] [PMID: 14848451]
[30]
Monge, A.; Martinez-Merino, V.; Sanmartin, C.; Fernandez, F.J.; Ochoa, M.C.; Bellver, C.; Artigas, P.; Fernandez-Alvarez, E. 2-Arylamino-4-oxo-3, 4-dihydropyrido [2, 3-d] pyrimidines: synthesis and diuretic activity. Eur. J. Med. Chem., 1989, 24(3), 209-216.
[http://dx.doi.org/10.1016/0223-5234(89)90001-9]
[31]
Bruno, O.; Schenone, S.; Ranise, A.; Bondavalli, F.; Barocelli, E.; Ballabeni, V.; Chiavarini, M.; Bertoni, S.; Tognolini, M.; Impicciatore, M. New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: synthesis and pharmacological screening. Bioorg. Med. Chem., 2001, 9(3), 629-636.
[http://dx.doi.org/10.1016/S0968-0896(00)00272-8] [PMID: 11310597]
[32]
Stocks, M. The small molecule drug discovery process–from target selection to candidate selection; Introduction to Biological and Small Molecule Drug Research and Development, 2013, pp. 81-126.
[http://dx.doi.org/10.1016/B978-0-12-397176-0.00003-0]
[33]
Hafez, H.N.; El-Gazzar, A.R. Synthesis and biological evaluation of N-pyrazolyl derivatives and pyrazolopyrimidine bearing a biologically active sulfonamide moiety as potential antimicrobial agent. Molecules, 2016, 21(9), 1156.
[http://dx.doi.org/10.3390/molecules21091156] [PMID: 27589717]
[34]
Chandrasekaran, K. Biosimilarity versus manufacturing change: two distinct concepts. J. Chem. Pharm. Res., 2016, 8, 849-861.
[35]
Polaquini, C.R.; Torrezan, G.S.; Santos, V.R.; Nazaré, A.C.; Campos, D.L.; Almeida, L.A.; Silva, I.C.; Ferreira, H.; Pavan, F.R.; Duque, C.; Regasini, L.O. Antibacterial and antitubercular activities of cinnamylideneacetophenones. Molecules, 2017, 22(10), 1685.
[http://dx.doi.org/10.3390/molecules22101685] [PMID: 28994740]
[36]
Tamaian, R.; Moţ, A.; Silaghi-Dumitrescu, R.; Ionuţ, I.; Stana, A.; Oniga, O.; Nastasă, C.; Benedec, D.; Tiperciuc, B. Study of the relationships between the structure, lipophilicity and biological activity of some thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles. Molecules, 2015, 20(12), 22188-22201.
[http://dx.doi.org/10.3390/molecules201219841] [PMID: 26690402]
[37]
SwissADME. (Available from: http://www.swissadme.ch/)
[38]
PreADMET. (Available from: https://preadmet.bmdrc.kr/)
[39]
ProTox-II. (Available from: http://tox.charite.de/)
[40]
UCSF Chimera (Available from: https://www.cgl.ucsf.edu/chimera/)

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