Abstract
Piperazine is the heterocyclic nucleus and exhibits significant biological potential such as antipsychotic, antidepressant, antihistamine, anticancer, anti-anginal, cardioprotective, antiviral, and anti-inflammatory activity. As a result, it had been considered a crucial structural component in the majority of the therapeutic medications that were already on the market. Other issues that limit its use include solubility, limited bioavailability, cost-effectiveness, and a mismatch between the drug's pharmacokinetic and pharmacodynamic profiles. Literature describes structural modification in the piperazine moiety to create novel derivatives or analogues to solve the issues with currently marketed medications. Nature provides various bioactive components having piperazine nuclei in their core structure. The present review describes the potential of the piperazine nucleus present in natural bioactive components. So the study concludes that it is vital to concentrate on the structural characteristics of this scaffold, which opens the way for future research and may benefit pharmaceutical companies as well as medicinal chemists.
Graphical Abstract
[http://dx.doi.org/10.1016/j.jsps.2019.11.025] [PMID: 32042262]
[http://dx.doi.org/10.1039/C3OB42512F] [PMID: 24614952]
[http://dx.doi.org/10.14233/ajchem.2019.22042]
[http://dx.doi.org/10.1002/jhet.5570030423]
[http://dx.doi.org/10.1021/acs.orglett.6b02591] [PMID: 27736075]
[http://dx.doi.org/10.1039/C7NJ04039C]
[http://dx.doi.org/10.1039/C9RA07870C] [PMID: 35540608]
[http://dx.doi.org/10.1016/j.tetlet.2005.09.092]
[http://dx.doi.org/10.7439/ijasr.v1i1.1766]
[http://dx.doi.org/10.1016/j.ejmech.2015.07.026] [PMID: 26310894]
[http://dx.doi.org/10.1021/jm5004599] [PMID: 24814197]
[http://dx.doi.org/10.5155/eurjchem.2.2.193-199.282]
[http://dx.doi.org/10.2174/13895575113139990073] [PMID: 23895191]
[http://dx.doi.org/10.1080/13543776.2016.1189902] [PMID: 27177234]
[http://dx.doi.org/10.1016/S0016-5085(19)35792-0] [PMID: 13448284]
[http://dx.doi.org/10.1016/0223-5234(96)83975-4] [PMID: 22026937]
[http://dx.doi.org/10.1016/j.exppara.2011.02.025] [PMID: 21354139]
[http://dx.doi.org/10.1016/j.chemolab.2011.10.002]
[http://dx.doi.org/10.1111/tmi.12395] [PMID: 25308185]
[http://dx.doi.org/10.1016/j.ejmech.2006.10.009] [PMID: 17140705]
[http://dx.doi.org/10.1016/j.bioorg.2019.103217] [PMID: 31479986]
[http://dx.doi.org/10.1007/s11458-009-0017-8]
[http://dx.doi.org/10.2174/157018012799079725]
[http://dx.doi.org/10.3906/kim-1806-7]
[http://dx.doi.org/10.2174/1871520615666141216151101] [PMID: 25511511]
[http://dx.doi.org/10.1016/S0022-4804(63)80014-1] [PMID: 13932216]
[http://dx.doi.org/10.1155/2013/653962] [PMID: 24288651]
[http://dx.doi.org/10.1155/2016/5878410]
[PMID: 2608706]
[http://dx.doi.org/10.1111/fcp.12408] [PMID: 30151922]
[http://dx.doi.org/10.1055/a-1323-2813] [PMID: 33336346]
[http://dx.doi.org/10.1002/anie.200200553] [PMID: 12973759]
[http://dx.doi.org/10.1002/ptr.7099] [PMID: 33847440]
[http://dx.doi.org/10.1021/jm5000497] [PMID: 24611879]
[http://dx.doi.org/10.1016/j.bioorg.2019.103060] [PMID: 31229796]
[http://dx.doi.org/10.1016/j.ejmech.2018.02.066] [PMID: 29501940]
[http://dx.doi.org/10.1016/j.ejmech.2015.03.051] [PMID: 25841199]
[http://dx.doi.org/10.1016/j.steroids.2014.09.007] [PMID: 25456170]
[http://dx.doi.org/10.1007/s13738-015-0762-1]
[http://dx.doi.org/10.1016/j.sjbs.2015.09.005] [PMID: 28053569]
[http://dx.doi.org/10.3184/174751915X14381686689721]
[http://dx.doi.org/10.1016/j.bmcl.2017.07.078] [PMID: 28789891]
[http://dx.doi.org/10.1016/j.bmcl.2017.02.066] [PMID: 28285912]
[http://dx.doi.org/10.3390/molecules180911496] [PMID: 24048283]
[http://dx.doi.org/10.1016/j.ejmech.2012.04.028] [PMID: 22677031]
[http://dx.doi.org/10.1016/j.ejmech.2015.04.063] [PMID: 25965778]
[http://dx.doi.org/10.1002/ardp.201900051] [PMID: 31339585]
[http://dx.doi.org/10.1039/C5RA20197G]
[http://dx.doi.org/10.6023/cjoc201708031]
[http://dx.doi.org/10.1002/cjoc.201100693]
[http://dx.doi.org/10.1016/j.bmcl.2016.12.076] [PMID: 28117202]
[http://dx.doi.org/10.1002/cmdc.201900541] [PMID: 31674147]
[http://dx.doi.org/10.1016/j.bioorg.2019.03.047] [PMID: 30904813]
[http://dx.doi.org/10.1016/j.ejmech.2012.08.048] [PMID: 23124210]
[http://dx.doi.org/10.1515/hc-2015-0025]
[http://dx.doi.org/10.1080/14756366.2019.1655407] [PMID: 31448648]
[http://dx.doi.org/10.1016/j.phymed.2013.03.015] [PMID: 23669265]
[http://dx.doi.org/10.1039/C5OB00406C] [PMID: 25895604]
[http://dx.doi.org/10.1007/s10600-011-0051-x]
[http://dx.doi.org/10.1016/j.bmc.2014.09.048] [PMID: 25306465]
[http://dx.doi.org/10.1016/j.bmcl.2012.08.071] [PMID: 22981334]
[http://dx.doi.org/10.1111/cbdd.12839] [PMID: 27860280]
[http://dx.doi.org/10.1016/j.bmcl.2016.01.088] [PMID: 26906636]
[http://dx.doi.org/10.1002/ps.5841] [PMID: 32246577]
[http://dx.doi.org/10.1002/ps.5822] [PMID: 32187443]
[http://dx.doi.org/10.1016/j.bmcl.2014.02.027] [PMID: 24594353]
[http://dx.doi.org/10.1016/j.bmcl.2016.12.008] [PMID: 28011213]
[http://dx.doi.org/10.1016/j.ejmech.2017.08.002] [PMID: 28803048]
[http://dx.doi.org/10.1016/j.bmcl.2019.08.026] [PMID: 31444084]
[http://dx.doi.org/10.4155/fmc-2018-0206] [PMID: 30273015]
[http://dx.doi.org/10.1016/j.bioorg.2019.103513] [PMID: 31884144]
[http://dx.doi.org/10.1016/j.bmc.2011.07.033] [PMID: 21840724]
[http://dx.doi.org/10.1016/j.ejmech.2013.09.024] [PMID: 24095756]
[http://dx.doi.org/10.1111/cbdd.13194] [PMID: 29543387]
[http://dx.doi.org/10.1016/j.ejmech.2013.04.015] [PMID: 23835481]
[http://dx.doi.org/10.1016/j.bmc.2017.12.016] [PMID: 29269256]
[http://dx.doi.org/10.1016/j.ejmech.2014.01.012] [PMID: 24487191]
[http://dx.doi.org/10.1016/j.ejmech.2009.12.006] [PMID: 20045220]
[http://dx.doi.org/10.1111/cbdd.12981] [PMID: 28328173]
[http://dx.doi.org/10.1016/j.bmc.2012.11.014] [PMID: 23245804]
[http://dx.doi.org/10.1021/jm901216v] [PMID: 19957999]
[http://dx.doi.org/10.1002/cjoc.201700272]
[http://dx.doi.org/10.1016/j.bmcl.2014.02.032] [PMID: 24613165]
[http://dx.doi.org/10.1016/j.tetlet.2016.11.059]
[http://dx.doi.org/10.3390/molecules28062511] [PMID: 36985486]
[http://dx.doi.org/10.1002/cbdv.202300208] [PMID: 36960853]
[http://dx.doi.org/10.3390/molecules28041717] [PMID: 36838705]
[http://dx.doi.org/10.1039/D2MD00116K] [PMID: 36092140]