Abstract
Diabetes is a growing health concern worldwide because it affects people of all age groups and increases the risk of other diseases such as renal impairment and neural and cardiovascular disorders. Oral hypoglycemic drugs mainly control diabetes; however, their associated side effects limit their use in patients with other complications. PTP1B is a viable drug target to explore new antidiabetic drugs. PTP1B acts as a negative regulator of the insulin-signaling pathway, and therefore, PTP1B inhibitors display antihyperglycemic activity. Several classes of compounds from natural and synthetic sources act as PTP1B inhibitors. Fungi are comprehensive in their diversity and recognized as a valuable source for therapeutically active molecules. In recent years, researchers have reported diverse classes of fungal secondary metabolites as potent PTP1B inhibitors. Some metabolites such as 6-O-methylalaternin, fumosorinone A, nordivaricatic acid, and the divarinyl divarate showed good activity and can be taken forward as a lead to develop novel PTP1B inhibitors and antidiabetic drugs. Therefore, the present review focuses on the fungal metabolites identified in the last five years possessing PTP1B inhibitory activity. A total of 128 metabolites are reviewed. Their fungal species and source, chemical structure, and activity in terms of IC50 are highlighted.
Keywords: Fungi, secondary metabolites, PTP1B inhibitors, anti-diabetic, diabetes, BMI.
Graphical Abstract
[http://dx.doi.org/10.1038/s41598-020-71908-9] [PMID: 32901098]
[http://dx.doi.org/10.1016/j.ejmech.2020.112376] [PMID: 32416458]
[http://dx.doi.org/10.1126/science.283.5407.1544] [PMID: 10066179]
[http://dx.doi.org/10.1016/j.bbapap.2009.09.018] [PMID: 19782770]
[http://dx.doi.org/10.1038/nrm1837] [PMID: 16493415]
[http://dx.doi.org/10.1016/j.beem.2007.08.004] [PMID: 18054739]
[http://dx.doi.org/10.3390/molecules26185505] [PMID: 34576982]
[PMID: 33892608]
[http://dx.doi.org/10.1080/14786419.2018.1499629] [PMID: 30445849]
[http://dx.doi.org/10.1080/10286020.2017.1385604] [PMID: 28990801]
[http://dx.doi.org/10.1186/s12934-021-01527-0] [PMID: 33579268]
[http://dx.doi.org/10.1016/j.bioorg.2020.103646] [PMID: 32036160]
[http://dx.doi.org/10.1039/C9QO00775J]
[http://dx.doi.org/10.3390/md15060191] [PMID: 28635658]
[http://dx.doi.org/10.1007/s11418-018-1193-y] [PMID: 29508256]
[http://dx.doi.org/10.1016/j.bmcl.2015.06.026] [PMID: 26115570]
[http://dx.doi.org/10.1007/s11418-017-1094-5] [PMID: 28550651]
[http://dx.doi.org/10.1016/j.fitote.2017.08.002] [PMID: 28807715]
[http://dx.doi.org/10.3390/md18050247] [PMID: 32397523]
[http://dx.doi.org/10.1021/acs.orglett.9b01751] [PMID: 31188002]
[http://dx.doi.org/10.1021/acs.jnatprod.9b00620] [PMID: 31469560]
[http://dx.doi.org/10.1038/ja.2015.44] [PMID: 25899128]
[http://dx.doi.org/10.1080/14786419.2017.1346642] [PMID: 28670919]
[http://dx.doi.org/10.1038/s41429-018-0034-2] [PMID: 29463888]
[http://dx.doi.org/10.1038/s41429-019-0187-7] [PMID: 31019257]
[http://dx.doi.org/10.3390/molecules25173927] [PMID: 32867374]
[http://dx.doi.org/10.3390/md18030132 ] [PMID: 32110865]
[http://dx.doi.org/10.3390/md19020082] [PMID: 33540563]
[http://dx.doi.org/10.1039/C9OB00534J] [PMID: 31041978]
[http://dx.doi.org/10.1007/s10600-019-02892-4]
[http://dx.doi.org/10.1021/acsomega.0c03315] [PMID: 33073119]
[http://dx.doi.org/10.1021/acs.jnatprod.9b00210] [PMID: 31710490]
[http://dx.doi.org/10.1016/j.bmc.2017.01.048] [PMID: 28202316]
[http://dx.doi.org/10.1515/znc-2014-4217]
[http://dx.doi.org/10.1016/j.fgb.2015.03.009] [PMID: 25857260]
[http://dx.doi.org/10.3390/molecules22122058] [PMID: 29186763]
[http://dx.doi.org/10.1016/j.fitote.2019.104342] [PMID: 31479703]
[http://dx.doi.org/10.1016/j.phytochem.2021.112664] [PMID: 33524855]
[http://dx.doi.org/10.1039/D1RA00788B]
[http://dx.doi.org/10.1016/j.bioorg.2020.103893] [PMID: 32492551]
[http://dx.doi.org/10.1016/j.phytochem.2019.112224] [PMID: 31812919]
[http://dx.doi.org/10.1016/j.lfs.2016.11.012] [PMID: 27871946]
[http://dx.doi.org/10.1016/j.bmcl.2017.06.001] [PMID: 28642102]
[http://dx.doi.org/10.1039/D0QO00851F]
[http://dx.doi.org/10.1021/acs.jnatprod.9b01108] [PMID: 31898904]
[http://dx.doi.org/10.1016/j.tetlet.2015.12.111]
[http://dx.doi.org/10.1038/ja.2017.72] [PMID: 28655930]
[http://dx.doi.org/10.1038/ja.2016.147] [PMID: 28074056]
[http://dx.doi.org/10.1007/s11418-016-1061-6] [PMID: 27866320]
[http://dx.doi.org/10.6023/cjoc201905010]
[http://dx.doi.org/10.3389/fchem.2020.00279] [PMID: 32373585]
[http://dx.doi.org/10.1055/s-0041-111629] [PMID: 26872321]
[http://dx.doi.org/10.1016/j.fitote.2016.04.007] [PMID: 27085303]
[http://dx.doi.org/10.1016/j.tet.2015.10.068]
[http://dx.doi.org/10.1021/jm990560c] [PMID: 10753467]
[http://dx.doi.org/10.1016/j.bmcl.2013.10.002] [PMID: 24148325]