Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins
Piperine (PN), the primary pungent alkaloid in black pepper shows several biological activities such as antioxidant, antimicrobial and anti-cancerogenic effects. Similar to other alkaloids, PN is characterized by poor water solubility. One way to improve its solubility and thus its biological activi...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/12/1762 |
| _version_ | 1827641628731375616 |
|---|---|
| author | Elias Christoforides Athena Andreou Andreas Papaioannou Kostas Bethanis |
| author_facet | Elias Christoforides Athena Andreou Andreas Papaioannou Kostas Bethanis |
| author_sort | Elias Christoforides |
| collection | DOAJ |
| description | Piperine (PN), the primary pungent alkaloid in black pepper shows several biological activities such as antioxidant, antimicrobial and anti-cancerogenic effects. Similar to other alkaloids, PN is characterized by poor water solubility. One way to improve its solubility and thus its biological activities is by forming inclusion complexes with suitable cyclodextrins. In this work PN inclusion complexes in native <i>β-</i>cyclodextrin (<i>β-</i>CD), its methylated (randomly methylated (RM-<i>β-</i>CD), heptakis-(2,6-di-<i>O</i>-methyl)-<i>β</i>-CD (DM-<i>β-</i>CD) and heptakis-(2,3,6-tri-<i>O</i>-methyl)-<i>β</i>-CD (TM-<i>β-</i>CD)) and 2-hydroxypropylated (HP-<i>β-</i>CD) derivatives are investigated using physicochemical methods, such as phase solubility study and X-ray crystallography complemented by theoretical (molecular dynamics simulations) studies. The determination of the crystal structure of the PN inclusion complexes in <i>β-</i>CD, DM-<i>β-</i>CD and TM-<i>β-</i>CD, reveals the formation of 1:2 guest:host inclusion complexes in the crystalline state. The guest PN molecule threads the hydrophobic cavities of the hosts which are arranged as couples in a tail-to-tail mode in the case of PN/<i>β-</i>CD and in a head-to-tail mode in the cases of PN/DM-<i>β-</i>CD and PN/TM-<i>β-</i>CD. MD studies based on the crystallographically determined structures and docked models show the stability of the examined complexes in an aqueous environment whereas the binding affinity of PN for the host molecules is calculated by the MM/GBSA method. Finally, phase-solubility studies of PN with <i>β-</i>CD, RM-<i>β-</i>CD and HP-<i>β-</i>CD are presented, indicating a B<sub>s</sub>-type for the PN/<i>β-</i>CD complex and an A<sub>L</sub>-type for the PN/RM-<i>β-</i>CD and PN/HP-<i>β-</i>CD complexes with 1:1 guest:host stoichiometry. |
| first_indexed | 2024-03-09T17:17:30Z |
| format | Article |
| id | doaj.art-a510b78ceb2a43cab59c344c971793f6 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T17:17:30Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a510b78ceb2a43cab59c344c971793f62023-11-24T13:32:53ZengMDPI AGBiomolecules2218-273X2022-11-011212176210.3390/biom12121762Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-CyclodextrinsElias Christoforides0Athena Andreou1Andreas Papaioannou2Kostas Bethanis3Physics Laboratory, Department of Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, GreeceGenetics Laboratory, Department of Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, GreecePhysics Laboratory, Department of Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, GreecePhysics Laboratory, Department of Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, GreecePiperine (PN), the primary pungent alkaloid in black pepper shows several biological activities such as antioxidant, antimicrobial and anti-cancerogenic effects. Similar to other alkaloids, PN is characterized by poor water solubility. One way to improve its solubility and thus its biological activities is by forming inclusion complexes with suitable cyclodextrins. In this work PN inclusion complexes in native <i>β-</i>cyclodextrin (<i>β-</i>CD), its methylated (randomly methylated (RM-<i>β-</i>CD), heptakis-(2,6-di-<i>O</i>-methyl)-<i>β</i>-CD (DM-<i>β-</i>CD) and heptakis-(2,3,6-tri-<i>O</i>-methyl)-<i>β</i>-CD (TM-<i>β-</i>CD)) and 2-hydroxypropylated (HP-<i>β-</i>CD) derivatives are investigated using physicochemical methods, such as phase solubility study and X-ray crystallography complemented by theoretical (molecular dynamics simulations) studies. The determination of the crystal structure of the PN inclusion complexes in <i>β-</i>CD, DM-<i>β-</i>CD and TM-<i>β-</i>CD, reveals the formation of 1:2 guest:host inclusion complexes in the crystalline state. The guest PN molecule threads the hydrophobic cavities of the hosts which are arranged as couples in a tail-to-tail mode in the case of PN/<i>β-</i>CD and in a head-to-tail mode in the cases of PN/DM-<i>β-</i>CD and PN/TM-<i>β-</i>CD. MD studies based on the crystallographically determined structures and docked models show the stability of the examined complexes in an aqueous environment whereas the binding affinity of PN for the host molecules is calculated by the MM/GBSA method. Finally, phase-solubility studies of PN with <i>β-</i>CD, RM-<i>β-</i>CD and HP-<i>β-</i>CD are presented, indicating a B<sub>s</sub>-type for the PN/<i>β-</i>CD complex and an A<sub>L</sub>-type for the PN/RM-<i>β-</i>CD and PN/HP-<i>β-</i>CD complexes with 1:1 guest:host stoichiometry.https://www.mdpi.com/2218-273X/12/12/1762piperine<i>β</i>-cyclodextrinmethylated <i>β</i>-cyclodextrin2-hydroxypropyl-<i>β</i>-cyclodextrininclusion complexmolecular dynamics |
| spellingShingle | Elias Christoforides Athena Andreou Andreas Papaioannou Kostas Bethanis Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins Biomolecules piperine <i>β</i>-cyclodextrin methylated <i>β</i>-cyclodextrin 2-hydroxypropyl-<i>β</i>-cyclodextrin inclusion complex molecular dynamics |
| title | Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins |
| title_full | Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins |
| title_fullStr | Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins |
| title_full_unstemmed | Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins |
| title_short | Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins |
| title_sort | structural studies of piperine inclusion complexes in native and derivative β cyclodextrins |
| topic | piperine <i>β</i>-cyclodextrin methylated <i>β</i>-cyclodextrin 2-hydroxypropyl-<i>β</i>-cyclodextrin inclusion complex molecular dynamics |
| url | https://www.mdpi.com/2218-273X/12/12/1762 |
| work_keys_str_mv | AT eliaschristoforides structuralstudiesofpiperineinclusioncomplexesinnativeandderivativebcyclodextrins AT athenaandreou structuralstudiesofpiperineinclusioncomplexesinnativeandderivativebcyclodextrins AT andreaspapaioannou structuralstudiesofpiperineinclusioncomplexesinnativeandderivativebcyclodextrins AT kostasbethanis structuralstudiesofpiperineinclusioncomplexesinnativeandderivativebcyclodextrins |