Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted)propanamides as promising antibacterial agents with mild cytotoxicity

Ghulam Hussain¹, Muhammad A Abbasi¹ , Aziz-ur-Rehman ¹, Sabahat Z Siddiqui¹, Irshad Ahmad², Rabia Malik², Muhammad Shahid³, Zahid Mushtaq³, Syed AA Shah^4,5

¹Department of Chemistry, Government College University, Lahore-54000; ²Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur-63100; ³Department of Biochemistry, University of Agriculture, Faisalabad-38040, Pakistan; ⁴Faculty of Pharmacy; ⁵Atta-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.

For correspondence:- Muhammad Abbasi Email: abbasi@gcu.edu.pk

Accepted: 15 June 2018 Published: 28 July 2018

Citation: Hussain G, Abbasi MA, A, Siddiqui SZ, Ahmad I, Malik R, et al. Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted)propanamides as promising antibacterial agents with mild cytotoxicity. Trop J Pharm Res 2018; 17(7):1397-1406 doi: 10.4314/tjpr.v17i7.25

© 2018 The authors.
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Abstract

Purpose: To evaluate the antibacterial activity and cytotoxicity of a series of molecules with amalgamation of furoyl, piperazine and amide moieties.

Methods: New derivatives, namely 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted) propanamides, were synthesized and evaluated for their antibacterial activity and toxicity to mammalian cells. The synthesis was initiated by treating different aryl/aralkyl amines (1a-u) with 3-bromopropionyl chloride (2) to obtain the solid electrophiles 3a-u, which were collected by filtration. Thereafter, the different N-aryl/aralkyl-3-bromopropionamides (3a-u) and 2-furoyl-1-piperazine (4) at equimolar ratios were allowed to react in acetonitrile and in the presence of a base, K₂CO₃, to form the target compounds, 5a-u. Structural elucidation was carried out using EI-MS (electron impact mass spectrometry), IR (infrared) and 1H-NMR (proton nuclear magnetic resonance). The antibacterial activity of the synthesized compounds was evaluated against various bacterial strains. Furthermore, hemolysis was determined to assess cytotoxicity using bovine red blood cells.

Results: Molecules 5g, 5a, 5p, 5g and 5i were found to be potent agents against S. aureus, S. typhi, P. aeruginosa, E. coli and B. subtilis with respective minimum inhibitory concentration (MIC) values of 8.34 ± 0.55, 8.37 ± 0.12, 8.65 ± 0.57, 8.97 ± 0.12 and 9.24 ± 0.50 µM, compared to 7.80 ± 0.19, 7.45 ± 0.58, 7.14 ± 0.58, 7.16 ± 0.58 and 7.29 ± 0.90 µM for the reference standard, ciprofloxacin. The most active compounds, 5a, 5g, 5i and 5p, showed a hemolysis of 15.48, 8.03, 5.52 and 4.35 %, respectively.

Conclusion: The synthesized compounds exhibit good antibacterial activity. The hemolysis data indicate that these compounds have a low toxicity level. However, in vivo studies are required to ascertain their potentials as new drug candidates.

Keywords: 4-(2-Furoyl)-1-piperazine, 1H-NMR, EI-MS, Antimicrobial activity, Hemolytic activity