Novel Piperazine Derivatives as Potent Antihistamine, Anti-Inflammatory, and Anticancer Agents, their Synthesis and Characterization
- Authors: Rasheed A.1, Shetty K.1, Roy L.1, Kumar J.1
-
Affiliations:
- Department of Chemistry, M.S. Ramaiah University of Applied Sciences
- Issue: Vol 24, No 14 (2024)
- Pages: 1063-1073
- Section: Oncology
- URL: https://rjsocmed.com/1871-5206/article/view/643845
- DOI: https://doi.org/10.2174/0118715206295673240409071016
- ID: 643845
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Abstract
Introduction:In this study, a series of novel piperazine derivatives were synthesised with high-to-good yields, and their structural analogies were confirmed using FTIR, 1H-NMR, and LC-MS techniques.
Methods:The synthesised compounds were evaluated for antioxidant and antimicrobial activities. Among the four synthesised piperazine derivatives, compound PD-2 exhibited relatively good antioxidant activity, with an IC50 value of 2.396 µg/mL, while the other three derivatives showed moderate to low antioxidant activity. Furthermore, compound PD-2 displayed antimicrobial activity against Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a fungus. However, all four compounds showed strong resistance against grampositive bacteria, Staphylococcus aureus.
Results:Additionally, compound PD-1 exhibited significant antihistamine activity, eliciting an 18.22% reduction in histamine levels. Both PD-1 and PD-2 demonstrated noteworthy anti-inflammatory activity in a dosedependent manner (5-10 µM), leading to the inhibition of nitrite production up to 39.42% and 33.7% at higher concentrations (10 µM) and inhibition of tumour necrosis factor-alpha (TNF-α) generation up to 56.97% and 44.73% at 10 µM, respectively. Additionally, both novel molecules PD-1 and PD-2 effectively restrained the growth of HepG2 cells in a manner that is dependent on the dosage up to 55.44% and 90.45% at the highest concentrations (100 µg/mL), respectively.
Conclusion:These findings substantiate the rationale for further investigation into the novel series of persuasive piperazine analogues as potential agents with anti-inflammatory, antihistamine and anticancer properties.
Keywords
About the authors
Ameer Rasheed
Department of Chemistry, M.S. Ramaiah University of Applied Sciences
Email: info@benthamscience.net
Kannika Shetty
Department of Chemistry, M.S. Ramaiah University of Applied Sciences
Email: info@benthamscience.net
Lairikyengbam Roy
Department of Chemistry, M.S. Ramaiah University of Applied Sciences
Author for correspondence.
Email: info@benthamscience.net
Jyotsna Kumar
Department of Chemistry, M.S. Ramaiah University of Applied Sciences
Author for correspondence.
Email: info@benthamscience.net
References
- Singh, N.; Pandurangan, A.; Rana, K.; Anand, P.; Ahamad, A.; Tiwari, A.K. Benzimidazole: A short review of their antimicrobial activities. Int. Curr. Pharm. J., 2012, 1(5), 110-118. doi: 10.3329/icpj.v1i5.10284
- Omar, A.Z.; Alshaye, N.A.; Mosa, T.M.; El-Sadany, S.K.; Hamed, E.A.; El-Atawy, M.A. Synthesis and antimicrobial activity screening of piperazines bearing N,N'-Bis(1,3,4-thiadiazole) moiety as probable enoyl-ACP reductase inhibitors. Molecules, 2022, 27(12), 3698. doi: 10.3390/molecules27123698 PMID: 35744824
- Chandra, S.; Chatterjee, P.; Dey, P.; Bhattacharya, S. Evaluation of in vitro anti-inflammatory activity of coffee against the denaturation of protein. Asian Pac. J. Trop. Biomed., 2012, 2(1), S178-S180. doi: 10.1016/S2221-1691(12)60154-3
- Al-Ghorbani, M.; Gouda, M.A.; Baashen, M.; Alharbi, O.; Almalki, F.A.; Ranganatha, L.V. Piperazine heterocycles as potential anticancer agents: A review. Pharm. Chem. J., 2022, 56(1), 29-37. doi: 10.1007/s11094-022-02597-z
- Zhang, R.H.; Guo, H.Y.; Deng, H.; Li, J.; Quan, Z.S. Piperazine skeleton in the structural modification of natural products: A review. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 1165-1197. doi: 10.1080/14756366.2021.1931861 PMID: 34080510
- Zhanel, G.G.; Walkty, A.; Vercaigne, L.; Karlowsky, J.A.; Embil, J.; Gin, A.S.; Hoban, D.J. The new fluoroquinolones: A critical review. Can. J. Infect. Dis., 1999, 10(3), 207-238. doi: 10.1155/1999/378394 PMID: 22346384
- Krishnamurthy, G.; Roy, D.; Kumar, J. Curcumin, a natural golden drug and its anticancer aspects from synthesis to delivery: A review. Int. J. Appl. Pharmaceut., 2020, 12(5), 70-84. doi: 10.22159/ijap.2020v12i5.38586
- Gillard, M.; Van Der Perren, C.; Moguilevsky, N.; Massingham, R.; Chatelain, P. Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: Contribution of Lys(191) and Thr(194). Mol. Pharmacol., 2002, 61(2), 391-399. doi: 10.1124/mol.61.2.391 PMID: 11809864
- Krishnamurthy, G.; Roy, D.L.; Kumar, J.; Gour, P.; Arland, S.E.; Prabu, M.; Gr, S.; Mt, S. Study of in-silico ADMET, molecular docking, and stability potential of synthesized novel tetrazole bearing curcumin derivatives and evaluation of their anticancer potential on PANC-1 cell lines. Rasayan J. Chem., 2023, 16(1), 335-354. doi: 10.31788/RJC.2023.1618114
- Jaehne, E.J.; Corrigan, F.; Toben, C.; Jawahar, M.C.; Baune, B.T. The effect of the antipsychotic drug quetiapine and its metabolite norquetiapine on acute inflammation, memory and anhedonia. Pharmacol. Biochem. Behav., 2015, 135, 136-144. doi: 10.1016/j.pbb.2015.05.021 PMID: 26047769
- Krishnamurthy, G.; Deepti Roy, L.; Kumar, J.; Gour, P.; Arland, S.E.; Rehman, N.; Gr, S.; Mt, S.; Shreenivas, M.T. Design, preparation, and in silico study of novel curcumin-biphenyl carbonitrile conjugate as novel anticancer drug molecules. Int. J. Appl. Pharmaceut., 2023, 15(4), 143-159. doi: 10.22159/ijap.2023v15i4.45811
- Borukhova, S.; Noël, T.; Hessel, V. Continuous-flow multistep synthesis of cinnarizine, cyclizine, and a buclizine derivative from bulk alcohols. ChemSusChem, 2016, 9(1), 67-74. doi: 10.1002/cssc.201501367 PMID: 26663906
- Singh, K.; Siddiqui, H.H.; Shakya, P.; Kumar, A.; Khalid, M.; Arif, M.; Alok, S. Piperazine-A biologically active scaffold. Int. J. Pharm. Sci. Res., 2015, 6(11), 4145. doi: 10.13040/IJPSR.0975-8232.6(10).4145-58
- Busbee, B.; Reichel, E.; Busbee, B. A novel lidocaine hydrochloride ophthalmic gel for topical ocular anesthesia. Local Reg. Anesth., 2010, 3, 57-63. doi: 10.2147/LRA.S6453 PMID: 22915870
- Munteanu, I.G.; Apetrei, C. Analytical methods used in determining antioxidant activity: A review. Int. J. Mol. Sci., 2021, 22(7), 3380. doi: 10.3390/ijms22073380 PMID: 33806141
- Roy, L.D.; Kumar, J.; Krishnamurthy, G.; Gour, P.; Arland, S.E.; Rahman, N. Phytogenic one-pot synthesis and spectroscopic characterization of novel mono benzylated resveratrol hybrid molecule using extracted resveratrol from green grape peels: In silico ADMET study and in vitro antitumor activities against breast cancer cells. Curr. Bioact. Compd., 2023, 19(8), e110523216810. doi: 10.2174/1573407219666230511150434
- Benzie, I.F.F.; Strain, J.J. Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol., 1999, 299, 15-27. doi: 10.1016/S0076-6879(99)99005-5 PMID: 9916193
- Liu, L.; Dai, H.; Wu, Y.; Li, B.; Yi, J.; Xu, C.; Wu, X. In vitro and in vivo mechanism of hepatocellular carcinoma inhibition by β-TCP nanoparticles. Int. J. Nanomedicine, 2019, 14, 3491-3502. doi: 10.2147/IJN.S193192 PMID: 31190806
- Roy, L.D.; Kumar, J.; Jays, J.; Krishnamurthy, G.; Gour, P.; Arland, S.E. Novel resveratrol analogues with aromatic hetero moieties: Designing, one-pot synthesis and in vitro biological evaluation. Farmacia, 2023, 71(1), 130-143. doi: 10.31925/farmacia.2023.1.16
- Sadalge, P.R.; Karnawadi, V.; Roy, D.L.; Prabu, M.; Krishnamurthy, G.; Gour, P.; Arland, S.E.; Kumar, J. Synthesis, characterization, and biological activity of novel azole piperazine congeners. J. Appl. Pharm. Sci., 2022, 13(4), 53-69. doi: 10.7324/JAPS.2023.58094
- Andersson, M.; Nolte, H.; Olsson, M.; Skov, P.; Pipkorn, U. Measurement of histamine in nasal lavage fluid: Comparison of a glass fiber-based fluorometric method with two radioimmunoassays1. J. Allergy Clin. Immunol., 1990, 86(5), 815-820. doi: 10.1016/S0091-6749(05)80188-5 PMID: 2229845
- Majeed, M.; Nagabhushanam, K.; Lawrence, L.; Nallathambi, R.; Thiyagarajan, V.; Mundkur, L. Boswellia serrata extract containing 30% 3-acetyl-11-keto-boswellic acid attenuates inflammatory mediators and preserves extracellular matrix in collagen-induced arthritis. Front. Physiol., 2021, 12, 735247. doi: 10.3389/fphys.2021.735247 PMID: 34650445
- Omar, A.Z.; Mosa, T.M.; Sadany, E.S.K.; Hamed, E.A.; Atawy, E.M. Novel piperazine based compounds as potential inhibitors for SARS-CoV-2 protease enzyme: Synthesis and molecular docking study. J. Mol. Struct., 2021, 1245, 131020. doi: 10.1016/j.molstruc.2021.131020 PMID: 34248201
- Sultana, N.; Arayne, M.S.; Shamshad, H.; Mirza, A.Z.; Naz, M.A.; Fatima, B.; Asif, M.; Mesaik, M.A. Synthesis, characterization and biological activities of cetirizine analogues. Spectroscopy , 2011, 26(4-5), 317-328. doi: 10.1155/2011/291720
- Magaldi, S.; Essayag, M.S.; de Capriles, H.C.; Pérez, C.; Colella, M.T.; Olaizola, C.; Ontiveros, Y. Well diffusion for antifungal susceptibility testing. Int. J. Infect. Dis., 2004, 8(1), 39-45. doi: 10.1016/j.ijid.2003.03.002 PMID: 14690779
- Hatnapure, G.D.; Keche, A.P.; Rodge, A.H.; Birajdar, S.S.; Tale, R.H.; Kamble, V.M. Synthesis and biological evaluation of novel piperazine derivatives of flavone as potent anti-inflammatory and antimicrobial agent. Bioorg. Med. Chem. Lett., 2012, 22(20), 6385-6390. doi: 10.1016/j.bmcl.2012.08.071 PMID: 22981334
- Fox, J.B. Kinetics and mechanisms of the Griess reaction. Anal. Chem., 1979, 51(9), 1493-1502. doi: 10.1021/ac50045a032
- Wang, P.; Cui, J.; Wen, J.; Guo, Y.; Zhang, L.; Chen, X. Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway. Oncol. Lett., 2016, 12(6), 4605-4612. doi: 10.3892/ol.2016.5288 PMID: 28105167
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