Synthesis and structure-activity relationship of 1-[(E)-3-phenyl-2-propenyl] piperazine derivatives as suitable antibacterial agents with mild hemolysis

Document Type : Article

Authors

1 Department of Chemistry, Government College University, Lahore-54000, Pakistan.

2 Faculty of Pharmacy and Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia

3 Department of Biochemistry, University of Agriculture, Faisalabad-38040, Pakistan

Abstract

A new series of 1-[(E)-3-phenyl-2-propenyl]piperazine derivatives (5a-m) as antibacterial agents was designed and synthesized. The synthetic strategy was initiated by coupling different anilines (1a-m) with bromoacetyl bromide (2) in aqueous basic medium to acquire different electrophiles, 3a-m, with good yields. These electrophiles were further reacted with 1-[(E)-3-phenyl-2-propenyl]piperazine (4) to yield the desired compounds, N-(substituted)-2-{4-[(E)-3-phenyl-2-propenyl]-1-perazinyl}acetamides (5a-m). The structures of these compounds were established from their IR, 1H-NMR, 13C-NMR, EI-MS and CHN analysis data. The bacterial biofilm inhibitory potential of these piperazine derivatives was tested against two pathogenic strains, Bacillus subtilus and Escherichia coli. Two compounds, 5d and 5h were identified as suitable antibacterial agents. The cytotoxicity of these molecules was profiled through hemolytic assay and it was inferred that all the compounds were nearly harmless for membrane of red blood cells.

Keywords

References

References:
1. Andonova, L., Zheleva-Dimitrova, D., Georgieva, M., and Zlatkov, A. "Synthesis and antioxidant activity of some 1-aryl/aralkyl piperazine derivatives with xanthine moiety at N4", Biotechnol. Biotechnological Equip., 28(6), pp. 1165-1171  2014). http://dx.doi.org/10.1080/13102818.2014.979978.
2. Mohsen, U.A. "Synthesis and antimicrobial activity of some piperazine dithiocarbamate derivatives", Turk. J. Pharm. Sci., 11(3), pp. 347-354 (2014).
3. Abbasi, M.A., Anwar, A., Aziz-ur-Rehman, Siddiqui, S.Z., Rubab, K., Shah, S.A.A., Lodhi, M.A., Khan, F.A., Ashraf, M., and Alam, U. "Synthesis, enzyme inhibition and molecular docking studies on 1- arylsulfonyl-4-phenylpiperazine derivatives", Pak. J. Pharm. Sci., 30(5), pp. 1715-1724 (2017).
4. Prakash, O., Gautam, P., Dani, R.K., Nandi, A., Singh, N.K., Singh, R.K. "Structural analysis of complexes formed by ethyl 4-phenylthiocarbamoyl piperazine-1-carboxylate with Ni(II), Zn(II) and Cd(II) through spectroscopic and DFT techniques", J.
Mol. Struct., 1063, pp. 184-191 (2014).
5. Abbasi, M.A., Hussain, G., Aziz-ur-Rehman, Siddiqui, S.Z., Shah, S.A.A., Lodhi, M.A., Khan, F.A., Ashraf, M., Qurat-ul-Aain, Ahmad, I., Malik, R., Shahid, M., and Mushtaq, Z. "Synthesis of some unique carbamate derivatives bearing 2-furoyl-1-piperazine as valuable therapeutic agent", Acta Chim. Slov., 64, pp. 159-169 (2017).
6. Nayak, P.S., Narayana, B., Sarojini, B.K., Fernandes, J., and Akshatha "Design, synthesis and biological evaluation of 2-(4-phenylpiperazin-1-yl)-N-(pyrazin-2- yl)acetamide as DPPH scavenging, analgesic and antiin  ammatory agent", J. Single Mol. Res., 2(2), pp. 20-26 (2014). 7. Abbasi, M.A., Hassan, M., Aziz-ur-Rehman, Siddiqui, S.Z., Hussain, G., Shah, S.A.A., Ashraf, M., Shahid, M., Seo, S.-Y. "2-furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer's diseases: In vitro and in silico studies", Comp. Bio. Chem., 77, pp. 72-86 (2018).
8. Albericio, F., "Developments in peptide and amide synthesis", Curr. Opin. Chem. Biol., 8, pp. 211-221 (2004).
9. Hussain, G., Abbasi, M.A., Aziz-ur-Rehman, Siddiqui, S.Z., Ashraf, M., Noreen, A., Lodhi, M.A., Khan, F.A., Shahid, M., Mushtaq, Z., and Shah, S.A.A. "Synthesis and molecular docking study of some new 4-f[4-(2-furoyl)-1-piperazinyl]methylg-N- (substituted-phenyl)benzamides as possible therapeutic entrants for Alzheimer's disease", Med. Chem. (Los Angeles), 6(2), pp. 129-136 (2016).
10. Hussain, G., Abbasi, M.A., Aziz-ur-Rehman, Siddiqui, S.Z., Shah, S.A.A. Ahmad, I., and Shahid, M. "Synthesis of some new 2-[4-(2-furoyl)-1-piperazinyl]- N-aryl/aralkyl acetamides as potent antibacterial agents", Pak. J. Pharm. Sci., 31(3), pp. 857-866 (2018).
11. Stepanovic, S., Vukovic, D., Dakic, I., Savic, B., and Svabic-Vlahovic, M. "A modified microtiter-plate test for quantification of Staphylococcal biofilm formation", J. Micro. Meth., 40, pp. 175-179 (2000).
12. Shahid, S.A., Anwar, F., Shahid, M., Majeed, N., Azam, A., Bashir, M., Amin, M., Mahmood, Z., and Shakir, I. "Laser-assisted synthesis of Mn0:50Zn0:50 Fe2O4 nanomaterial: Characterization and in vitro inhibition activity towards Bacillus subtilis biofilm", J. Nanomater., 2015, pp. 1-6 Article ID: 896185 (2015). http://dx.doi.org/10.1155/2015/896185.
13. Abbasi, M.A., Massod, M., Aziz-ur-Rehman, Siddiqui, S.Z., Fatima, A., Shahid, M., Fatima, H., and Khan, K.M. "Synthesis of some 1,4-benzodioxane containing methanesulfonamides and their hemolytic study on human blood", J. Chem. Soc. Pak., 39(6), pp. 999- 1005 (2017).
14. Abbasi, M.A., Islam, M., Aziz-ur-Rehman, Rasool, S., Rubab, K., Hussain, G., Ahmad, I., Ashraf, M., Shahid, M., and Shah, S.A.A. "Synthesis, characterization, antibacterial, glucosidase inhibition and hemolytic studies on some new N- (2,3-dimethylphenyl)benzenesulfonamide derivatives", Trop. J. Pharm. Res., 15(3), pp. 591-598 (2016).
Scientia Iranica
Volume 26, Issue 6 - Serial Number 6
Transactions on Chemistry and Chemical Engineering (C)
November and December 2019
Pages 3375-3386

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History

  • Receive Date: 13 June 2018
  • Revise Date: 15 May 2019
  • Accept Date: 21 September 2019

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