Inhibitory effects of selected cannabinoids against dipeptidyl peptidase IV, an enzyme linked to type 2 diabetes
- Mkabayi, Lithalethu, Viljoen, Zenobia, Krause, Rui W M, Lobb, Kevin A, Pletschke, Brett I, Frost, Carminita L
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Krause, Rui W M , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2024
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452760 , vital:75168 , xlink:href="https://doi.org/10.1016/j.heliyon.2023.e23289"
- Description: Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme.
- Full Text:
- Date Issued: 2024
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Krause, Rui W M , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2024
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452760 , vital:75168 , xlink:href="https://doi.org/10.1016/j.heliyon.2023.e23289"
- Description: Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme.
- Full Text:
- Date Issued: 2024
Inhibiting human dipeptidyl peptidase IV using cannabinoids and Leonotis leonurus extracts as a potential therapy for the management of diabetes
- Mkabayi, Lithalethu, Viljoen, Zenobia, Lobb, Kevin A, Pletschke, Brett I, Frost, Carminita L
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452745 , vital:75167 , xlink:href="https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0043-1773924"
- Description: Diabetes is a chronic metabolic disorder that has been shown to affect a growing number of people worldwide. Controlling blood glucose levels is one of the possible strategies to treat type 2 diabetes mellitus (T2DM). It has been established that the inhibition of dipeptidyl peptidase IV (DPP-IV) prolongs the activity of incretin hormones, which serve as key stimulators of insulin secretion and regulation of blood glucose levels. Although several synthetic DPP-IV inhibitors are available, there is still a need for naturally sourced inhibitors that have fewer to no undesirable side effects. In this study, cannabinoids and Leonotis leonurus aqueous extracts were evaluated for their inhibitory effects against recombinant human DPP-IV. Their potential inhibition mechanism was explored using in vitro and in silico approaches. All tested cannabinoids and L. leonurus aqueous extracts showed significant inhibitory activity against DPP-IV. Phytochemical analysis of L. leonurus extract indicated the presence of diterpenoids and alkaloids, which might contribute to the inhibitory activity. In molecular docking studies, among different constituents known in L. leonurus, luteolin and marrubiin showed binding energy of -7.2 kcal/mol and cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) showed binding energies ranging from -6.5 to -8.2 kcal/mol. Molecular dynamics revealed that all tested compounds formed stable complexes with the enzyme during 100 ns simulation, indicating that they are good ligands. This study provided preliminary evidence for the potential application of the selected cannabinoids and L. leonurus in maintaining glucose homeostasis, suggesting that they could be suitable therapeutic candidates for managing T2DM.
- Full Text:
- Date Issued: 2023
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452745 , vital:75167 , xlink:href="https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0043-1773924"
- Description: Diabetes is a chronic metabolic disorder that has been shown to affect a growing number of people worldwide. Controlling blood glucose levels is one of the possible strategies to treat type 2 diabetes mellitus (T2DM). It has been established that the inhibition of dipeptidyl peptidase IV (DPP-IV) prolongs the activity of incretin hormones, which serve as key stimulators of insulin secretion and regulation of blood glucose levels. Although several synthetic DPP-IV inhibitors are available, there is still a need for naturally sourced inhibitors that have fewer to no undesirable side effects. In this study, cannabinoids and Leonotis leonurus aqueous extracts were evaluated for their inhibitory effects against recombinant human DPP-IV. Their potential inhibition mechanism was explored using in vitro and in silico approaches. All tested cannabinoids and L. leonurus aqueous extracts showed significant inhibitory activity against DPP-IV. Phytochemical analysis of L. leonurus extract indicated the presence of diterpenoids and alkaloids, which might contribute to the inhibitory activity. In molecular docking studies, among different constituents known in L. leonurus, luteolin and marrubiin showed binding energy of -7.2 kcal/mol and cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) showed binding energies ranging from -6.5 to -8.2 kcal/mol. Molecular dynamics revealed that all tested compounds formed stable complexes with the enzyme during 100 ns simulation, indicating that they are good ligands. This study provided preliminary evidence for the potential application of the selected cannabinoids and L. leonurus in maintaining glucose homeostasis, suggesting that they could be suitable therapeutic candidates for managing T2DM.
- Full Text:
- Date Issued: 2023
Synthesis, characterization, computational studies and DPPH scavenging activity of some triazatetracyclic derivatives
- Odame, Felix, Hosten, Eric C, Betz, Richard, Krause, Jason, Frost, Carminita L, Lobb, Kevin A, Tshentu, Zenixole R
- Authors: Odame, Felix , Hosten, Eric C , Betz, Richard , Krause, Jason , Frost, Carminita L , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/451186 , vital:75026 , xlink:href="https://doi.org/10.1007/s13738-021-02158-3"
- Description: Some dihydrobenzo[4,5]imidazo[1,2-c]quinazolines have been synthesized from aldehydes and ketones, using the ketones as both reagents and solvents and tetrahydrofuran (THF) as the solvent for the aldehydes, to yield the triazatetracyclics. The compounds have been characterized with spectroscopy and microanalysis. The crystal structures of 9,9-dimethyl-8,10,17- triazatetracyclo[8.7.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaene (I), 9-butyl-9-methyl-8,10,17-triazatetracyclo[8.7.0.02 , 7 .011,16]heptadeca-(17),2,4,6,11(16),12,14-heptaene (III) and 9-phenyl-8,10,17-triazatetracyclo[8.7.0 02 7.011,16] heptadeca-1(17),2,4,6,11(16),12,14-heptaene (VIII) have been discussed. The computed NMR, IR, molecular electrostatic potential and frontier molecular orbitals of compounds I, III and VIII have been discussed. The M06 functional gave most of its values closest to the experimental values for the bond lengths and bond angles of compounds I and III. For compound VIII, none of the functionals gave values for bond lengths and bond angles that were consistent with the experimental values, but M06 gave values closest to experimental values. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity of the triazatetracyclics showed that compound I exhibits signifcant DPPH scavenging activity with an IC50 of 56.18 µM compared to 2.37 µM for ascorbic acid.
- Full Text:
- Date Issued: 2021
- Authors: Odame, Felix , Hosten, Eric C , Betz, Richard , Krause, Jason , Frost, Carminita L , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/451186 , vital:75026 , xlink:href="https://doi.org/10.1007/s13738-021-02158-3"
- Description: Some dihydrobenzo[4,5]imidazo[1,2-c]quinazolines have been synthesized from aldehydes and ketones, using the ketones as both reagents and solvents and tetrahydrofuran (THF) as the solvent for the aldehydes, to yield the triazatetracyclics. The compounds have been characterized with spectroscopy and microanalysis. The crystal structures of 9,9-dimethyl-8,10,17- triazatetracyclo[8.7.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaene (I), 9-butyl-9-methyl-8,10,17-triazatetracyclo[8.7.0.02 , 7 .011,16]heptadeca-(17),2,4,6,11(16),12,14-heptaene (III) and 9-phenyl-8,10,17-triazatetracyclo[8.7.0 02 7.011,16] heptadeca-1(17),2,4,6,11(16),12,14-heptaene (VIII) have been discussed. The computed NMR, IR, molecular electrostatic potential and frontier molecular orbitals of compounds I, III and VIII have been discussed. The M06 functional gave most of its values closest to the experimental values for the bond lengths and bond angles of compounds I and III. For compound VIII, none of the functionals gave values for bond lengths and bond angles that were consistent with the experimental values, but M06 gave values closest to experimental values. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity of the triazatetracyclics showed that compound I exhibits signifcant DPPH scavenging activity with an IC50 of 56.18 µM compared to 2.37 µM for ascorbic acid.
- Full Text:
- Date Issued: 2021
Synthesis, characterization and biological activity of some Dithiourea Derivatives:
- Odame, Felix, Hosten, Eric C, Krause, Jason, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D, Sayed, Yasien, Frost, Carminita L, Lobb, Kevin A, Tshentu, Zenixole R
- Authors: Odame, Felix , Hosten, Eric C , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita L , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
- Authors: Odame, Felix , Hosten, Eric C , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita L , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
Synthesis, characterization and DPPH scavenging activity of some benzimidazole derivatives
- Odame, Felix, Krause, Jason, Hosten, Eric C, Betz, Richard, Lobb, Kevin A, Tshentu, Zenixole R, Frost, Carminita L
- Authors: Odame, Felix , Krause, Jason , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R , Frost, Carminita L
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447209 , vital:74592 , xlink:href="https://dx.doi.org/10.4314/bcse.v32i2.8 "
- Description: A base-catalyzed conversion of aldehydes to benzimidazoles has been achieved. The compounds have been characterized by IR, NMR, micoranalysis, and GC-MS. The reaction for the formation of benzimidazoles has been monitored with 1 H NMR and IR. The crystal structures of two derivatives, 2-(2- chlorophenyl)-1H-benzimidazole and 2-(1H-benzimidazol-2-yl)-4-nitrophenol, are presented. A study of the DPPH scavenging activity of these compounds showed that 2-(1H-benzimidazol-2-yl)phenol (2), 2-p-tolyl-1Hbenzimidazole (3) and 2-(4-methoxyphenyl)-1H-benzimidazole (7) gave IC50 values 1974, 773 and 800 µM.
- Full Text:
- Date Issued: 2018
- Authors: Odame, Felix , Krause, Jason , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R , Frost, Carminita L
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447209 , vital:74592 , xlink:href="https://dx.doi.org/10.4314/bcse.v32i2.8 "
- Description: A base-catalyzed conversion of aldehydes to benzimidazoles has been achieved. The compounds have been characterized by IR, NMR, micoranalysis, and GC-MS. The reaction for the formation of benzimidazoles has been monitored with 1 H NMR and IR. The crystal structures of two derivatives, 2-(2- chlorophenyl)-1H-benzimidazole and 2-(1H-benzimidazol-2-yl)-4-nitrophenol, are presented. A study of the DPPH scavenging activity of these compounds showed that 2-(1H-benzimidazol-2-yl)phenol (2), 2-p-tolyl-1Hbenzimidazole (3) and 2-(4-methoxyphenyl)-1H-benzimidazole (7) gave IC50 values 1974, 773 and 800 µM.
- Full Text:
- Date Issued: 2018
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