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

Synthesis and Biological Evaluation of Cholic Acid Tagged Piperazine Derivatives

Author(s): Dima W. Alshawabkeh, Anas J. Rasras*, Saqr Abushattal, Mohammad S. Al Zubi, Mohamad M. Shakdofa, Eyad A. Younes and Raed A. Al-Qawasmeh*

Volume 28, Issue 1, 2024

Published on: 23 January, 2024

Page: [65 - 73] Pages: 9

DOI: 10.2174/0113852728281288240109113216

Price: $65

Abstract

Diseases caused by bacteria are a big challenge for scientists worldwide. These bacteria can be resistant through the adaption of new ways to protect themselves against antimicrobial drugs and thus become multidrug resistance. In this work, new derivatives of 1,3,4-oxadiazole- cholic acid were synthesized and fully characterized using different techniques, such as 1H-NMR, 13C-NMR, and HRMS. Their biological activity, along with the measuring of their minimal inhibitory concentration (MIC), was studied and reported. The antimicrobial activity of the new library was assessed via in vitro screening against both Gram-positive and Gram-negative bacteria. The compounds showed selectivity against Gram-positive bacteria. Among the new analogues, compounds 4F and 5h were found to be potent against S. aureus with MIC of 47 μg/mL. Compounds 4f, 5g and 5h were active against MRSE with MIC of 188, 99, and 23 μg/mL, respectively.

Keywords: Antibacterial, cholic acid, heterocyclic, piperazine, MRSA, anti-COVID-19.

« Previous Next »
Graphical Abstract

[1]
Antimicrobial resistance. Available from: https://www.who.int/newsroom/fact-sheets/detail/antibiotic-resistance
[2]
Annunziato, G. Strategies to overcome antimicrobial resistance (AMR)making use of non-essential target inhibitors: A review. Int. J. Mol. Sci., 2019, 20(23), 5844.
[http://dx.doi.org/10.3390/ijms20235844] [PMID: 31766441]
[3]
Hrast, M. Design and preparation of antimicrobial agents. Antibiotics, 2022, 11(12), 1778.
[http://dx.doi.org/10.3390/antibiotics11121778] [PMID: 36551435]
[4]
Carryn, S.; Chanteux, H.; Seral, C.; Mingeot-Leclercq, M.P.; Van Bambeke, F.; Tulkens, P.M. Intracellular pharmacodynamics of antibiotics. Infect. Dis. Clin. North Am., 2003, 17(3), 615-634.
[http://dx.doi.org/10.1016/S0891-5520(03)00066-7] [PMID: 14711080]
[5]
(a) Jampilek, J. Heterocycles in medicinal chemistry. Molecules, 2019, 24(21), 3839.
[http://dx.doi.org/10.3390/molecules24213839] [PMID: 31731387];
(b) Heravi, M.M.; Zadsirjan, V. Prescribed drugs containing nitrogen heterocycles: An overview. RSC Advances, 2020, 10(72), 44247-44311.
[http://dx.doi.org/10.1039/D0RA09198G] [PMID: 35557843]
[6]
(a) Wang, Q.; Mgimpatsang, K.C.; Konstantinidou, M.; Shishkina, S.V.; Dömling, A. 1,3,4-oxadiazoles by Ugi-tetrazole and huisgen reaction. Org. Lett., 2019, 21(18), 7320-7323.
[http://dx.doi.org/10.1021/acs.orglett.9b02614] [PMID: 31478379];
(b) Glomb, T.; Wiatrak, B.; Gębczak, K.; Gębarowski, T.; Bodetko, D.; Czyżnikowska, Ż.; Świątek, P. New 1,3,4-oxadiazole derivatives of pyridothiazine-1,1-dioxide with anti-inflammatory activity. Int. J. Mol. Sci., 2020, 21(23), 9122.
[http://dx.doi.org/10.3390/ijms21239122] [PMID: 33266208];
(c) Hossan, A.; Abumelha, H.M.; Alnoman, R.B.; Bayazeed, A.; Alsoliemy, A.; Keshk, A.A.; El-Metwaly, N.M. Synthesis, self-assembly and opticalproperties of novel fluorescent alkoxy-substituted fluoroaryl 1,3,4-oxadiazoleorganogelator. Arab. J. Chem., 2022, 15(5), 103771.
[http://dx.doi.org/10.1016/j.arabjc.2022.103771];
(d) Mamatha, S.V.; Belagali, S.L.; Bhat, M. Synthesis, characterisation andevaluation of oxadiazole as promising anticancer agent. SN Appl. Sci., 2020, 2(5), 882.
[http://dx.doi.org/10.1007/s42452-020-2511-z];
(e) Schwärzer, K.; Tüllmann, C.P.; Graßl, S.; Górski, B.; Brocklehurst, C.E.; Knochel, P. Functionalization of 1,3,4-oxadiazoles and 1,2,4-triazoles via selective zincation or magnesiation using 2,2,6,6-tetramethylpiperidyl bases. Org. Lett., 2020, 22(5), 1899-1902.
[http://dx.doi.org/10.1021/acs.orglett.0c00238] [PMID: 32048510];
(f) Umair, M.; Aziz-ur-Rehman,; Abbasi, M.A.; Siddiqui, S.Z.; Iqbal, J.; Rasool, S.; Khan, S.U.; Shah, S.A.A. Multi-selective reaction of azinane bearingoxadiazoles and substituted haloalkanes catalyzed by alkali metal hydrideto access anti-enzymatic agents. J. Mol. Struct., 2024, 1297, 136936.
[http://dx.doi.org/10.1016/j.molstruc.2023.136936]
[7]
Rabie, A.M. Two antioxidant 2,5-disubstituted-1,3,4-oxadiazoles (CoViTris2020 and ChloViD2020): successful repurposing against COVID-19 as thefirst potent multitarget anti-SARS-CoV-2 drugs. New J. Chem., 2021, 45(2), 761-771.
[http://dx.doi.org/10.1039/D0NJ03708G]
[8]
(a) Han, X.; Yu, Y.L.; Ma, D.; Zhang, Z.Y.; Liu, X.H. Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 345-361.
[http://dx.doi.org/10.1080/14756366.2020.1864630] [PMID: 33356666];
(b) Stecoza, C.E.; Nitulescu, G.M.; Draghici, C.; Caproiu, M.T.; Olaru, O.T.; Bostan, M.; Mihaila, M. Synthesis and anticancer evaluation of new 1,3,4-oxadiazole derivatives. Pharmaceuticals, 2021, 14(5), 438.
[http://dx.doi.org/10.3390/ph14050438] [PMID: 34066442];
(c) El Mansouri, A.E.; Maatallah, M.; Ait Benhassou, H.; Moumen, A.; Mehdi, A.; Snoeck, R.; Andrei, G.; Zahouily, M.; Lazrek, H.B. Design, synthesis, chemical characterization, biological evaluation, and docking study of new 1,3,4-oxadiazole homonucleoside analogs. Nucleosides Nucleotides Nucleic Acids, 2020, 39(8), 1088-1107.
[http://dx.doi.org/10.1080/15257770.2020.1761982] [PMID: 32397827]
[9]
Rasras, A.J.; El-Naggar, M.; Safwat, N.A.; Al-Qawasmeh, R.A. Cholyl 1,3,4-oxadiazole hybrid compounds: Design, synthesis and antimicrobial assessment. Beilstein J. Org. Chem., 2022, 18, 631-638.
[http://dx.doi.org/10.3762/bjoc.18.63] [PMID: 35706993]
[10]
(a) Biernacki, K.; Daśko, M.; Ciupak, O.; Kubiński, K.; Rachon, J.; Demkowicz, S. Novel 1,2,4-oxadiazole derivatives in drug discovery. Pharmaceuticals, 2020, 13(6), 111.
[http://dx.doi.org/10.3390/ph13060111] [PMID: 32485996];
(b) Kapadiya, K.; Dholaria, P. Microwave and conventional study of coumarin-oxadiazole adducts and their anti-microbial evaluation. Folia Med., 2021, 63(1), 105-112.
[http://dx.doi.org/10.3897/folmed.63.e52655] [PMID: 33650403]
[11]
Al-Wahaibi, L.H.; Mohamed, A.A.B.; Tawfik, S.S.; Hassan, H.M.; El-Emam, A.A. 1,3,4-oxadiazole N-mannich bases: Synthesis, antimicrobial,and anti-proliferative activities. Molecules, 2021, 26(8), 2110.
[http://dx.doi.org/10.3390/molecules26082110] [PMID: 33916955]
[12]
Taha, M.; Ismail, N.H.; Imran, S.; Rokei, M.Q.B.; Saad, S.M.; Khan, K.M. Synthesis of new oxadiazole derivatives as α-glucosidase inhibitors. Bioorg. Med. Chem., 2015, 23(15), 4155-4162.
[http://dx.doi.org/10.1016/j.bmc.2015.06.060] [PMID: 26183542]
[13]
Rasras, A.J.; Al-Qawasmeh, R.A.; El-Naggar, M.; Shehadi, I.; Elaasser, M.M.; Al-Soud, Y.A. Design, synthesis and antimicrobial assessments of aminoacetylenic-piperazine nitroimidazole hybrid compounds. Z. Naturforsch. C J. Biosci., 2023, 78(3-4), 113-121.
[http://dx.doi.org/10.1515/znc-2022-0043] [PMID: 35942947]
[14]
(a) Rashid, S.A.; Norman, N.; Teo, S.H.; Tong, W.Y.; Leong, C.R.; Tan, W.N.; Noor, M.A.M. Cholic acid: A novel steroidal uncompetitive inhibitor against β-lactamase produced by multidrug-resistant isolates. World J. Microbiol. Biotechnol., 2021, 37(9), 152.
[http://dx.doi.org/10.1007/s11274-021-03118-y] [PMID: 34398332];
(b) Cunningham, A.J.; Gibson, V.P.; Banquy, X.; Zhu, X.X.; Jeanne, L.C. Cholic acid-based mixed micelles as siRNA delivery agents for gene therapy. Int. J. Pharm., 2020, 578, 119078.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119078] [PMID: 31988037];
(c) Wang, M.Q.; Zhang, K.H.; Liu, F.L.; Zhou, R.; Zeng, Y.; Chen, A.L.; Yu, Y.; Xia, Q.; Zhu, C.C.; Lin, C.Z. Wedelolactone alleviates cholestatic liver injury by regulating FXR-bile acid-NF-κB/NRF2 axis to reduce bile acid accumulation and its subsequent inflammation and oxidative stress. Phytomedicine, 2024, 122, 155124.
[http://dx.doi.org/10.1016/j.phymed.2023.155124] [PMID: 38014837];
(d) Shanmugam, C.; Marimuthu, V.; Rajendiran, N. Photo-induced synthesisof star poly(DL-Lactide)-templated Au and Ag nanoparticles and evaluationof their catalytic performance. React. Funct. Polym., 2024, 194, 105772.
[http://dx.doi.org/10.1016/j.reactfunctpolym.2023.105772];
(e) Du, Y.; Wang, G.; Yu, E.; Xie, J.; Xia, Y.; Li, H.; Zhang, K.; Gong, W.; Li, Z.; Xie, W.; Jiang, P.; Zhang, W.; Shao, L.; Tian, J. Dietary deoxycholicacid decreases fat accumulation by activating liver farnesoid X receptor ingrass crap (Ctenopharyngodon idella). Aquaculture, 2024, 578, 740123.
[http://dx.doi.org/10.1016/j.aquaculture.2023.740123];
(f) Jin, C.; Zhou, T.; Duan, Z.; Deng, Y.; Zhang, X.; Xiao, C.; He, J.; He, G.; Zhou, Y.; Li, S. Effect of chin brick tea [Camellia sinensis (L.) Kuntze] on lipid metabolism and inflammation by modulating intestinal flora and bile acids in mice with non-alcoholic fatty liver disease. J. Ethnopharmacol., 2024, 318(Pt B), 116950.
[http://dx.doi.org/10.1016/j.jep.2023.116950] [PMID: 37506781]
[15]
(a) Rasras, A.J.M.; Al-Tel, T.H.; Al-Aboudi, A.F.; Al-Qawasmeh, R.A. Synthesis and antimicrobial activity of cholic acid hydrazone analogues. Eur. J. Med. Chem., 2010, 45(6), 2307-2313.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.006] [PMID: 20181416];
(b) Yadav, K.; Yavvari, P.S.; Pal, S.; Kumar, S.; Mishra, D.; Gupta, S.; Mitra, M.; Soni, V.; Khare, N.; Sharma, P.; Srikanth, C.V.; Kapil, A.; Singh, A.; Nandicoori, V.K.; Bajaj, A. Oral delivery of cholic acid-derived amphiphilehelps in combating salmonella-mediated gut infection and inflammation. Bioconjug. Chem., 2019, 30(3), 721-732.
[http://dx.doi.org/10.1021/acs.bioconjchem.8b00880] [PMID: 30669829];
(c) Gupta, S.; Thakur, J.; Pal, S.; Gupta, R.; Mishra, D.; Kumar, S.; Yadav, K.; Saini, A.; Yavvari, P.S.; Vedantham, M.; Singh, A.; Srivastava, A.; Prasad, R.; Bajaj, A. Cholic acid-peptide conjugates as potent antimicrobialsagainst interkingdom polymicrobial biofilms. Antimicrob. Agents Chemother., 2019, 63(11), e00520-19.
[http://dx.doi.org/10.1128/AAC.00520-19] [PMID: 31427303]
[16]
(a) Navacchia, M.L.; Marchesi, E.; Perrone, D. Bile acid conjugates withanticancer activity: Most recent research. Molecules, 2020, 26(1), 25.;
(b) Sreekanth, V.; Bansal, S.; Motiani, R.K.; Kundu, S.; Muppu, S.K.; Majumdar, T.D.; Panjamurthy, K.; Sengupta, S.; Bajaj, A. Design, synthesis, and mechanistic investigations of bile acid-tamoxifen conjugates for breast cancer therapy. Bioconjug. Chem., 2013, 24(9), 1468-1484.
[http://dx.doi.org/10.1021/bc300664k] [PMID: 23909664]
[17]
Chuchkov, K.; Chayrov, R.; Hinkov, A.; Todorov, D.; Shishkova, K.; Stankova, I.G. Modifications on the heterocyclic base of ganciclovir, penciclovir, acyclovir-syntheses and antiviral properties. Nucleosides Nucleotides Nucleic, 2020, 39(7), 979-990.
[http://dx.doi.org/10.1080/15257770.2020.1725043] [PMID: 32312162]
[18]
Abo-Ashour, M.F.; Eldehna, W.M.; George, R.F.; Abdel-Aziz, M.M.; Elaasser, M.M.; Abdel Gawad, N.M.; Gupta, A.; Bhakta, S.; Abou-Seri, S.M. Novel indole-thiazolidinone conjugates: Design, synthesis and whole-cell phenotypic evaluation as a novel class of antimicrobial agents. Eur. J. Med. Chem., 2018, 160, 49-60.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.008] [PMID: 30317025]

Rights & Permissions Print Cite
Article Metrics
23
3
© 2024 Bentham Science Publishers | Privacy Policy