Login Register Cart 0
Generic placeholder image

Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Design, Synthesis of Novel N-Substituted 6α-Piperazinomethyl-Δ4-3,17-diketosteroids and their Antimicrobial Activity Evaluation

Author(s): Nadejda K. Davydova*, Vladimir N. Sergeev, Alexander S. Peregudov, Anastasia E. Kuvarina, Vera S. Sadykova and Tatiana S. Savinova

Volume 27, Issue 15, 2023

Published on: 04 October, 2023

Page: [1365 - 1370] Pages: 6

DOI: 10.2174/0113852728262675230922050004

Price: $65

conference banner
Abstract

This report presents the synthesis of three innovative N-substituted 6α- piperazinomethyl-Δ4-3,17-diketo-steroids via the region-directed three-component condensation method. The compounds were produced from N-substituted piperazine derivatives and androst-4-en-3,17-dione (AD). Comprehensive physicochemical methods of analysis were employed to characterize the synthesized products. The study involved antibacterial testing of the synthesized compounds against Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, and Staphylococcus aureus 209P FDA, with a comparison to the amoxicillin/clavulanic acid composition. It further assessed antifungal activity against Aspergillus niger INA 00760, with results compared to amphotericin B and nystatin. Initial assessment of the antibacterial and antifungal activities exhibited by the synthesized compounds suggests that this series of N-substituted 6α-piperazinomethyl-Δ4-3,17-diketo-steroids holds great potential for further biological investigation.

« Previous Next »
Graphical Abstract

[1]
Roman, G. Mannich bases in medicinal chemistry and drug design. Eur. J. Med. Chem., 2015, 89, 743-816.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.076] [PMID: 25462280]
[2]
Pishawikar, S.A.; More, H.N. Synthesis, docking and in-vitro screening of mannich bases of thiosemicarbazide for anti-fungal activity. Arab. J. Chem., 2017, 10, S2714-S2722.
[http://dx.doi.org/10.1016/j.arabjc.2013.10.016]
[3]
Bala, S.; Sharma, N.; Kajal, A.; Kamboj, S.; Saini, V. An important pharmacophore in present scenario. Int. J. Med. Chem., 2014, 2014, 15.
[http://dx.doi.org/10.1155/2014/191072]
[4]
Tramontini, M.; Angiolini, L. Mannich bases: chemistry and uses; CRC Press. Inc, 1994, pp. 77-80.
[5]
McFadyen, I.J.; Houshyar, H.; Liu-Chen, L.Y.; Woods, J.H.; Traynor, J.R. The steroid 17α-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxy-pregna-3,5-dien-20-one (SC17599) is a selective μ-opioid agonist: Implications for the μ-opioid pharmacophore. Mol. Pharmacol., 2000, 58(4), 669-676.
[http://dx.doi.org/10.1124/mol.58.4.669] [PMID: 10999935]
[6]
Craig, C.R.; Sollman, P.B. 17-Oxygenated-3-ethoxy-6-(disubstituted aminomethyl) pregna-3,5-dien-20-ones and analgesic composition. US Patent 3534071,, 1970.
[7]
Perrone, M.G.; Bleve, L.; Santandrea, E.; Vitale, P.; Niso, M.; Scilimati, A. The tertiary amine nitrogen atom of piperazine sulfonamides as a novel determinant of potent and selective beta3-adrenoceptor agonists. ChemMedChem, 2009, 4(12), 2080-2097.
[http://dx.doi.org/10.1002/cmdc.200900292] [PMID: 19882697]
[8]
Savinova, T.S.; Lukashev, N.V.; Latyshev, G.V.; Sukhodolskaja, G.V.; Donova, M.V.; Fokina, V.V.; Shutov, A.A.; Nikolaeva, V.M.; Surovtsev, V.V. Method of producing 6-methyleneandrost-4-ene-3,17-dione from androst-4-ene-3,17-dione, method of producing 6-methyleneandrosta-1,4-diene-3,17-dione (exemestane) using obtained 6-methyleneandrost-4-ene-3,17-dione. RU Patent 2425052, 2011.
[9]
Savinova, T.S.; Kazantsev, A.V.; Lukashev, N.V. Method of preparing 6-(Nmethyl- N-phenyl)aminomethyl-hydrocortisone esters thereof from hydrocortisone 21-acetate. RU Patent 2663483, 2018.
[10]
Savinova, T.S.; Kazantsev, A.V.; Lukashev, N.V. Method of preparation 6α-methylenehydrocortisone or esters thereof from hydrocortisone 21-acetate. RU Patent 2664101,, 2018.
[11]
Savinova, T.S.; Kazantsev, A.V.; Lukashev, N.V. Method of preparation 6α-methylhydrocortisone or esters thereof from hydrocortisone 21-acetate. RU Patent 2663484,, 2018.
[12]
Savinova, T.S.; Kazantsev, A.V.; Lukashev, N.V.; Arinbasarova, A. Method of obtaining 6α-methylhydrocortisone or its 11β-alkanoyloxy-derivatives (versions), method of obtaining 6α-methylprednisole or its 11β-alkanoyloxyderivatives using obtained 6α-methylhydrocortizone or its 11β-alkanoyloxyderivatives. RU Patent 2337918,, 2009.
[13]
Sukhodolskaya, G.; Fokina, V.; Shutov, A.; Nikolayeva, V.; Savinova, T.; Grishin, Y.; Kazantsev, A.; Lukashev, N.; Donova, M. Bioconversion of 6-(N- methyl- N- phenyl)aminomethyl androstane steroids by Nocardioides simplex. Steroids, 2017, 118, 9-16.
[http://dx.doi.org/10.1016/j.steroids.2016.11.001] [PMID: 27864019]
[14]
Sharma, K.; Kumar, H. Priyanka. Formation of nitrogen-containing six-membered heterocycles on steroidal ring system: A review. Steroids, 2023, 191109171
[http://dx.doi.org/10.1016/j.steroids.2022.109171] [PMID: 36581085]
[15]
Davydova, N.K.; Marchenko, N.B.; Glushkov, R.G.; Peters, V.V.; Padeiskaya, E.N. Synthesis and antiprotozoal activity of some N-alkyl-3-nitroquinolones-4. Pharm. Chem. J., 1991, 25(10), 730-732.
[http://dx.doi.org/10.1007/BF00768988]
[16]
Glushkov, R.G.; Davydova, N.K. Chemistry of 3-nitroquinolines and their derivatives (review). Pharm. Chem. J., 1992, 26(4), 325-337.
[http://dx.doi.org/10.1007/BF00773165]
[17]
Glushkov, R.G.; Yuzhakov, S.D.; L’vov, A.I.; Zhikhareva, G.P.; Davydova, N.K.; Sizova, O.S.; Asnina, V.V.; Salin, E.N. New group of class III antiarrhythmic drugs: Piperid-4-ylethane derivatives. Pharm. Chem. J., 2011, 45(2), 65-74.
[http://dx.doi.org/10.1007/s11094-011-0562-6]
[18]
Davydova, N.K. Development of drug substances of the original class III antiarrhythmic drugs nibentan and niferidyl. Pharm. Chem. J., 2019, 53(9), 792-796.
[http://dx.doi.org/10.1007/s11094-019-02081-1]
[19]
Skachilova, S.Y.; Ermakova, G.A.; Zheltukhin, N.K.; Zueva, E.F.; Davydova, N.K. Drugs developed at “ARC BASS” with M.D. Mashkovskii lead (review). Drug. Develop. Regist., 2019, 8(1), 7-13.
[http://dx.doi.org/10.33380/2305-2066-2019-8-1-7-13]
[20]
Grinev, A.N.; Trofimov, F.A.; Tsyshkova, N.G.; Pershin, G.N.; Bogdanova, N.S.; Nikolaeva, I.S. Chlorohydrate of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-oxy-6-bromoindole having antivirus action and method for obtaining it. SU Patent 1685933,, 1991.
[21]
Padeiskaya, E.N.; Pershin, G.N.; Kostyuchenok, B.M.; Blatun, L.A.; Kulikov, Y.S.; Tagirov, R.F.; Gromov, M.V.; Pershin, G.G.; Makarenkova, R.V. Dioxidine, a new antibacterial drug for the treatment of suppurative infections. Pharm. Chem. J., 1977, 11(8), 1148-1154.
[http://dx.doi.org/10.1007/BF00778201]
[22]
Mishra, V.; Chundawat, T.S. Pd Catalyzed N1/N4 arylation of piperazine for synthesis of drugs, biological and pharmaceutical targets: An overview of buchwald hartwig amination reaction of piperazine in drug synthesis. Curr. Org. Synth., 2018, 15(2), 208-220.
[http://dx.doi.org/10.2174/1570179415666171206151603]
[23]
Andryushina, V.A.; Savinova, T.S.; Skrjabin, K.G. Method of synthesis of gamma-lactone of 3(7alpha-acetylthio-17beta-hydroxy-3-oxoandrost-4-ene-17alpha-yl)-propionic acid. RU Patent 2163606,, 2001.
[24]
Huang, C.; Shao, Z.; Wang, Y.; Wang, R.; Wang, B.; Wang, H.; Lei, L. Synthesis method of alkyl acid testosterone. CN Patent 111995650,, 2020.
[25]
Chaudhary, P.; Kumar, R.; Verma, A.K.; Singh, D.; Yadav, V.; Chhillar, A.K.; Sharma, G.L.; Chandra, R. Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine derivatives. Bioorg. Med. Chem., 2006, 14(6), 1819-1826.
[http://dx.doi.org/10.1016/j.bmc.2005.10.032] [PMID: 16289939]
[26]
Cao, H. Making process of disposable medicated disinfecting towel for sexual inter course. CN Patent 1297777, 2001.
[27]
Noga, E.J.; Barthalmus, G.T. Method of inhibiting the growth of melaninpigmented cells. US Patent 4859668, 1989.
[28]
EUCAST disk diffusion method for antimicrobial susceptibility testing. Available from:https://www.eucast.org/fileadmin/src/media/PDFs/EU-CAST_files/Disk_test_documents/2023_manuals/Manual_v_11.0_EUCAST_Disk_Test_2023.pdf (January 2023)
[29]
Kowalska-Krochmal, B.; Dudek-Wicher, R. The minimum inhibitory concentration of antibiotics: Methods, interpretation, clinical relevance. Pathogens, 2021, 10(2), 165.
[http://dx.doi.org/10.3390/pathogens10020165] [PMID: 33557078]
[30]
Yadav, V.; Mandhan, R.; Dabur, R.; Chhillar, A.K.; Gupta, J.; Sharma, G.L. A fraction from Escherichia coli with anti-aspergillus properties. J. Med. Microbiol., 2005, 54(4), 375-379.
[http://dx.doi.org/10.1099/jmm.0.45748-0] [PMID: 15770023]

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