European Journal of Chemistry

Synthesis, molecular docking, and biological evaluation of methyl-5-(hydroxyimino)-3-(aryl-substituted)hexanoate derivatives

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Published: Jun 30, 2022
DOI: https://doi.org/10.5155/eurjchem.13.2.151-161.2220
Keywords:
Cytotoxic, Antioxidant activity, Antibacterial activity, Anti-inflammatory activity, Beta-aryl ketohexanoic acid, Hydroxylamine hydrochloride
Section
Research Article
Issue
Vol. 13 No. 2 (2022): June 2022
Dates
Received 2021-12-10
Accepted 2022-04-03
Published 2022-06-30
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Parashuram Gudimani
Department of Chemistry, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0002-3131-1958
Samundeeswari Lokesh Shastri
Department of Chemistry, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0003-1035-7081
Varsha Pawar
Department of Chemistry, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0003-2096-9356
Nagashree Uday Hebbar
Department of Chemistry, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0002-8647-2724
Lokesh Anand Shastri
Department of Chemistry, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0002-5672-8442
Shrinivas Joshi
Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, Soniya Education Trusts College of Pharmacy, SangolliRayanna Nagar, Dharwad 580002, Karnataka, India
https://orcid.org/0000-0002-6520-806X
Shyam Kumar Vootla
Department of Biotechnology and Microbiology, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0002-7936-9825
Sheela Khanapure
Department of Biotechnology and Microbiology, Karnatak University, Dharwad 580003, Karnataka, India
https://orcid.org/0000-0002-4247-1658
Vinay Sunagar
Department of Chemistry, Govindram Seksaria Science College, Belagavi 590006, Karnataka, India
https://orcid.org/0000-0001-9804-7330

Abstract

Beta-aryl keto hexanoic acids (5a-l) were synthesized efficiently, followed by esterification that afforded beta-aryl keto methylhexanoates (6a-l). The chemo-selective ketoxime beta-aryl methyl hexanoates (7a-l) were isolated in good yields. Spectroscopic methods were used to characterize the obtained moieties. The antioxidant, anti-inflammatory, and antibacterial properties of the effectively synthesized compounds 7a-l were also investigated. The anti-inflammatory activity of the compounds 7c, 7f, 7i, and 7l was excellent, with a low IC50 value at micromolar concentration, which was much better than the reference diclofenac. All synthesized compounds 7a-l were assessed for their in vitro antibacterial activity against S. aureus, B. subtilis and E. coli.  Most of the compounds exhibited promising activity against Gram-positive bacterial strain, compound 7i showed excellent activity compared to standard streptomycin and in the case of E. coli, compounds 7b, 7c, 7j, 7k and 7l have shown moderate activity. Further, the cytotoxic activities of the compounds were assessed against lung cancer cells (A549) by using MTT assay. The possible interaction mechanism of the molecules 7c and 7g with Gram-negative strain E. coli DNA gyrase B in complex with PDB ID: 4DUH was studied.


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Gudimani, P.; Shastri, S. L.; Pawar, V.; Hebbar, N. U.; Shastri, L. A.; Joshi, S.; Vootla, S. K.; Khanapure, S.; Sunagar, V. Synthesis, Molecular Docking, and Biological Evaluation of Methyl-5-(hydroxyimino)-3-(aryl-substituted)hexanoate Derivatives. Eur. J. Chem. 2022, 13, 151-161.

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References

[1]. Nicolaou, K. C. Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory. Proc. Math. Phys. Eng. Sci. 2014, 470, 20130690.
https://doi.org/10.1098/rspa.2013.0690

[2]. Mo, X.; Morgan, T. D. R.; Ang, H. T.; Hall, D. G. Scope and mechanism of a true organocatalytic Beckmann rearrangement with a boronic acid/perfluoropinacol system under ambient conditions. J. Am. Chem. Soc. 2018, 140, 5264-5271.
https://doi.org/10.1021/jacs.8b01618

[3]. Koran, K.; Özen, F.; Biryan, F.; Görgülü, A. O. Synthesis, structural characterization and dielectric behavior of new oxime-cyclotriphosphazene derivatives. J. Mol. Struct. 2016, 1105, 135-141.
https://doi.org/10.1016/j.molstruc.2015.10.048

[4]. Xu, Y.; Yang, Q.; Li, Z.; Gao, L.; Zhang, D.; Wang, S.; Zhao, X.; Wang, Y. Ammoximation of cyclohexanone to cyclohexanone oxime using ammonium chloride as nitrogen source. Chem. Eng. Sci. 2016, 152, 717-723.
https://doi.org/10.1016/j.ces.2016.06.068

[5]. Sahyoun, T.; Arrault, A.; Schneider, R. Amidoximes and oximes: Synthesis, structure, and their key role as NO donors. Molecules 2019, 24, 2470.
https://doi.org/10.3390/molecules24132470

[6]. Saikia, L.; Baruah, J. M.; Thakur, A. J. A rapid, convenient, solventless green approach for the synthesis of oximes using grindstone chemistry. Org. Med. Chem. Lett. 2011, 1, 12.
https://doi.org/10.1186/2191-2858-1-12

[7]. Karthikeyan, P.; Aswar, S. A.; Muskawar, P. N.; Sythana, S. K.; Bhagat, P. R.; Kumar, S. S.; Satvat, P. S. A novel l-amino acid ionic liquid for quick and highly efficient synthesis of oxime derivatives - An environmental benign approach. Arab. J. Chem. 2016, 9, S1036-S1039.
https://doi.org/10.1016/j.arabjc.2011.11.007

[8]. Walton, J. Functionalised oximes: Emergent precursors for carbon-, nitrogen- and oxygen-centred radicals. Molecules 2016, 21, 63.
https://doi.org/10.3390/molecules21010063

[9]. Kozłowska, J.; Grela, E.; Baczyńska, D.; Grabowiecka, A.; Anioł, M. Novel O-alkyl derivatives of naringenin and their oximes with antimicrobial and anticancer activity. Molecules 2019, 24, 679.
https://doi.org/10.3390/molecules24040679

[10]. Pal, D.; Kumar, S.; Saha, S. Antihyperglycemic activity of phenyl and ortho-hydroxy phenyl linked imidazolyl triazolo hydroxamic acid derivatives. Int. J. Pharm. Pharm. Sci. 2017, 9, 247-251.
https://doi.org/10.22159/ijpps.2017v9i12.22086

[11]. Das, M.; Das, B.; Samanta, A. Antioxidant and anticancer activity of synthesized 4-amino-5-((aryl substituted)-4H-1,2,4-triazole-3-yl)thio-linked hydroxamic acid derivatives. J. Pharm. Pharmacol. 2019, 71, 1400-1411.
https://doi.org/10.1111/jphp.13131

[12]. Pepeljnjak, S.; Zorc, B.; Butula, I. Antimicrobial activity of some hydroxamic acids. Acta Pharm. 2005, 55, 401-408.

[13]. Yousif, M. N. M. Recent advances in chemistry and biological activity of 2,6-diphenyl piperidines. Mini Rev. Org. Chem. 2022, 19, 125-135.
https://doi.org/10.2174/1570193X18666210224153249

[14]. Dai, H.; Chen, J.; Li, H.; Dai, B.; He, H.; Fang, Y.; Shi, Y. Synthesis and bioactivities of novel pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety. Molecules 2016, 21, 276.
https://doi.org/10.3390/molecules21030276

[15]. Kozłowska, J.; Potaniec, B.; Żarowska, B.; Anioł, M. Synthesis and biological activity of novel O-alkyl derivatives of naringenin and their oximes. Molecules 2017, 22.
https://doi.org/10.3390/molecules22091485

[16]. Sammaiah, A.; Kaki, S. S.; Manoj, G. N. V. T. S.; Poornachandra, Y.; Kumar, C. G.; Prasad, R. B. N. Novel fatty acid esters of apocynin oxime exhibit antimicrobial and antioxidant activities: Novel bioactive lipophilic apocynin oxime esters. Eur. J. Lipid Sci. Technol. 2015, 117, 692-700.
https://doi.org/10.1002/ejlt.201400471

[17]. Gopalakrishnan, M.; Thanusu, J.; Kanagarajan, V. A facile solid-state synthesis and in vitro antimicrobial activities of some 2,6-diarylpiperidin/tetrahydrothiopyran and tetrahydropyran-4-one oximes. J. Enzyme Inhib. Med. Chem. 2009, 24, 669-675.
https://doi.org/10.1080/14756360802323902

[18]. Arthur-Santiago, M. A.; Oliart-Ros, R. M.; Sánchez-Otero, M. G.; Valerio-Alfaro, G. Mechanochemo-enzymatic Synthesis of Aromatic Aldehyde Oxime Ester. Nat. Prod. Commun. 2018, 13, 7, https://doi.org/ 10.1177/1934578X1801300723
https://doi.org/10.1177/1934578X1801300723

[19]. Flipo, M.; Charton, J.; Hocine, A.; Dassonneville, S.; Deprez, B.; Deprez-Poulain, R. Hydroxamates: relationships between structure and plasma stability. J. Med. Chem. 2009, 52, 6790-6802.
https://doi.org/10.1021/jm900648x

[20]. Giacomelli, G.; Porcheddu, A.; Salaris, M. Simple one-flask method for the preparation of hydroxamic acids. Org. Lett. 2003, 5, 2715-2717.
https://doi.org/10.1021/ol034903j

[21]. Jamal, S. A. A.; Jaser, B.; Hmadi, W. F.; Al-Obaidi, O. Preparation Some of Hydroxamic Acid Derivatives from Honey Wax Compounds and Study the Biological Activity on Cancerous Tumors. Sys. Rev. Pharm. 2020, 11 (2), 109-118.

[22]. Botta, C. B.; Cabri, W.; Cini, E.; De Cesare, L.; Fattorusso, C.; Giannini, G.; Persico, M.; Petrella, A.; Rondinelli, F.; Rodriquez, M.; Russo, A.; Taddei, M. Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: synthesis, biological activity, and computational evaluation. J. Med. Chem. 2011, 54, 2165-2182.
https://doi.org/10.1021/jm101373a

[23]. Tharini, K.; Sangeetha, P. Antioxidant and anti-inflammatory activity of 3,3-dimethyl 2,6-dimethyl piperidine 4-one oxime. Int. J. Chem. Sci. 2015, 13, 1794-1804. https://www.tsijournals.com/articles/anti oxidant-and-antiinflammatory-activity-of-33dimethyl-26dimethyl-piperidine-4one-oxime.pdf (accessed April 10, 2022).

[24]. El-Gamal, M. I.; Bayomi, S. M.; El-Ashry, S. M.; Said, S. A.; Abdel-Aziz, A. A.-M.; Abdel-Aziz, N. I. Synthesis and anti-inflammatory activity of novel (substituted)benzylidene acetone oxime ether derivatives: molecular modeling study. Eur. J. Med. Chem. 2010, 45, 1403-1414.
https://doi.org/10.1016/j.ejmech.2009.12.041

[25]. Naik, N. S.; Shastri, L. A.; Joshi, S. D.; Dixit, S. R.; Chougala, B. M.; Samundeeswari, S.; Holiyachi, M.; Shaikh, F.; Madar, J.; Kulkarni, R.; Sunagar, V. 3,4-Dihydropyrimidinone-coumarin analogues as a new class of selective agent against S . aureus : Synthesis, biological evaluation and molecular modelling study. Bioorg. Med. Chem. 2017, 25, 1413-1422.
https://doi.org/10.1016/j.bmc.2017.01.001

[26]. Mallesha, L.; Mohana, K. Synthesis and In Vitro Antimicrobial Activity of 2,4-Difluorophenyl (piperidin-4-yl)methanone Oxime Derivatives. Can. Chem. Trans. 2014, 343-352.
https://doi.org/10.13179/canchemtrans.2014.02.03.0121

[27]. Jebli, N.; Hamimed, S.; Van Hecke, K.; Cavalier, J.-F.; Touil, S. Synthesis, antimicrobial activity and molecular docking study of novel α-(diphenylphosphoryl)- and α-(diphenylphosphorothioyl)cycloal-kaneone oximes. Chem. Biodivers. 2020, 17, e2000217.
https://doi.org/10.1002/cbdv.202000217

[28]. Burcu, B.; Karaosmanoglu, O.; Dal, H.; Sivas, H.; Benkli, K. Synthesis of Some Aryl Ketoxime Derivatives with their in vitro Anti-microbial and Cytotoxic Activity. Glob. J. Cancer. Ther. 2019, 5 (1), 001-006.
https://doi.org/10.17352/gjct.000023

[29]. Premalatha, B.; Bhakiaraj, D.; Elavarasan, S.; Chellakili, B.; Gopalakrishnan, M. Synthesis, spectral analysis, in vitro microbiolo-gical evaluation and antioxidant properties of 2,4-diaryl-3-azabicyclo[3.3.1]nonane-9-one-O-[2,4,6-tritertiarybutyl-cyclohexa-2,5-dienon-4-yl] oximes as a new class of antimicrobial and anti-oxidant agents. J. Pharm. Res. 2013, 6, 730-735.
https://doi.org/10.1016/j.jopr.2013.07.007

[30]. Saxena, A.; Shastri, L.; Sunagar, V. Green approach for the synthesis of 4-coumarin-4H-pyrans from 4-formylcoumarins and their antibacterial study. Synth. Commun. 2017, 47, 1570-1576.
https://doi.org/10.1080/00397911.2017.1336557

[31]. Gudimani, P.; Shastri, S. L.; Pawar, V.; Shastri, L. A.; Sungar, V. A. Indirect, catalyst free β-arylation of acyclic 1,5-dicarbonyl compounds via green method. Chem. Data Coll. 2021, 33, 100692.
https://doi.org/10.1016/j.cdc.2021.100692

[32]. Sakat, S.; Juvekar, A.; Gambhire, M. In­vitro antioxidant and anti­inflammatory activity of methanol extract of Oxalis corniculata Linn. Int. J. Pharm. Pharm. Sci. 2010, 2, 146-155.

[33]. Mizushima, Y.; Kobayashi, M. Interaction of anti-inflammatory drugs with serum proteins, especially with some biologically active proteins. J. Pharm. Pharmacol. 1968, 20, 169-173.
https://doi.org/10.1111/j.2042-7158.1968.tb09718.x

[34]. Harini, S. T.; Kumar, H. V.; Rangaswamy, J.; Naik, N. Synthesis, antioxidant and antimicrobial activity of novel vanillin derived piperidin-4-one oxime esters: preponderant role of the phenyl ester substituents on the piperidin-4-one oxime core. Bioorg. Med. Chem. Lett. 2012, 22, 7588-7592.
https://doi.org/10.1016/j.bmcl.2012.10.019

[35]. Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 1999, 26, 1231-1237.
https://doi.org/10.1016/S0891-5849(98)00315-3

[36]. Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity-a rapid access to atomic charges. Tetrahedron 1980, 36, 3219-3228.
https://doi.org/10.1016/0040-4020(80)80168-2

[37]. Zhong, H.; Huang, W.; He, G.; Peng, C.; Wu, F.; Ouyang, L. Molecular dynamics simulation of tryptophan hydroxylase-1: binding modes and free energy analysis to phenylalanine derivative inhibitors. Int. J. Mol. Sci. 2013, 14, 9947-9962.
https://doi.org/10.3390/ijms14059947

[38]. Carmichael, J.; DeGraff, W. G.; Gazdar, A. F.; Minna, J. D.; Mitchell, J. B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987, 47, 936-942.

[39]. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65, 55-63.
https://doi.org/10.1016/0022-1759(83)90303-4

[40]. Alley, M. C.; Scudiero, D. A.; Monks, A.; Hursey, M. L.; Czerwinski, M. J.; Fine, D. L.; Abbott, B. J.; Mayo, J. G.; Shoemaker, R. H.; Boyd, M. R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988, 48, 589-601.

[41]. Scudiero, D. A.; Shoemaker, R. H.; Paull, K. D.; Monks, A.; Tierney, S.; Nofziger, T. H.; Currens, M. J.; Seniff, D.; Boyd, M. R. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res. 1988, 48, 4827-4833.

[42]. Blois, M. S. Antioxidant determinations by the use of a stable free radical. Nature 1958, 181, 1199-1200.
https://doi.org/10.1038/1811199a0

[43]. Zhang, S.-L.; Xie, H.-X.; Zhu, J.; Li, H.; Zhang, X.-S.; Li, J.; Wang, W. Organocatalytic enantioselective β-functionalization of aldehydes by oxidation of enamines and their application in cascade reactions. Nat. Commun. 2011, 2, 211.
https://doi.org/10.1038/ncomms1214

[44]. Xu, Y.; Yang, Q.; Li, Z.; Gao, L.; Zhang, D.; Wang, S.; Zhao, X.; Wang, Y. Ammoximation of cyclohexanone to cyclohexanone oxime using ammonium chloride as nitrogen source. Chem. Eng. Sci. 2016, 152, 717-723.
https://doi.org/10.1016/j.ces.2016.06.068

[45]. Alturiqi, A. S.; Alaghaz, A.-N. M. A.; Ammar, R. A.; Zayed, M. E. Synthesis, spectral characterization, and thermal and cytotoxicity studies of Cr(III), Ru(III), Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base derived from 5-hydroxymethylfuran-2-carbaldehyde. J. Chem. 2018, 2018, 1-17.
https://doi.org/10.1155/2018/5816906

[46]. Jean, B. P.; Franklin, R. C.; Patricia, A. B.; George, M. E.; Janet, A. H.; Stephen, G. J.; James, S. L.; Brandi, L.; Linda, A. M.; David, P. M.; Mair, P.; Jana, M. S.; Maria, M. T.; John, D. T.; Melvin, P. W.; Barbara, L. Z. Clinical and Laboratory Standards Institute Performance standards for antimicrobial disk susceptibility test twenty-fifth informational supplement; Committee for Clinical Laboratory Standards: Wayne PA, 2015.

[47]. Kahlmeter, G. The 2014 Garrod Lecture: EUCAST - are we heading towards international agreement? J. Antimicrob. Chemother. 2015, 70, 2427-2439.
https://doi.org/10.1093/jac/dkv145

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