Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling
A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (<b>1</b>), along with eight known compounds—voacangine (<b>2</b>), voacristine (<b>3</b>), coronaridine (<b>4</b>), tabernanthine (<b>5</b>), iboxygaine (<b>6<...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/1/70 |
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| author | Smith B. Babiaka Conrad V. Simoben Kennedy O. Abuga James A. Mbah Rajshekhar Karpoormath Dennis Ongarora Hannington Mugo Elvis Monya Fidelis Cho-Ngwa Wolfgang Sippl Edric Joel Loveridge Fidele Ntie-Kang |
| author_facet | Smith B. Babiaka Conrad V. Simoben Kennedy O. Abuga James A. Mbah Rajshekhar Karpoormath Dennis Ongarora Hannington Mugo Elvis Monya Fidelis Cho-Ngwa Wolfgang Sippl Edric Joel Loveridge Fidele Ntie-Kang |
| author_sort | Smith B. Babiaka |
| collection | DOAJ |
| description | A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (<b>1</b>), along with eight known compounds—voacangine (<b>2</b>), voacristine (<b>3</b>), coronaridine (<b>4</b>), tabernanthine (<b>5</b>), iboxygaine (<b>6</b>), voacamine (<b>7</b>), voacorine (<b>8</b>) and conoduramine (<b>9</b>)—were isolated from the stem bark of <i>Voacangaafricana</i>. The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>4</b>, <b>6</b>, <b>7</b> and <b>8</b> were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of <i>Onchocerca ochengi</i>, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC<sub>50</sub> values of the isolates are 2.49–5.49 µM for microfilariae and 3.45–17.87 µM for adult males. Homology modeling was used to generate a 3D model of the <i>O. ochengi</i> thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal structure–activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of <i>V. africana</i> in the treatment of human onchocerciasis. |
| first_indexed | 2024-03-10T13:46:53Z |
| format | Article |
| id | doaj.art-d98fcf0fe3e74b26922cbd1a7906ebc2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T13:46:53Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d98fcf0fe3e74b26922cbd1a7906ebc22023-11-21T02:35:20ZengMDPI AGMolecules1420-30492020-12-012617010.3390/molecules26010070Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular ModelingSmith B. Babiaka0Conrad V. Simoben1Kennedy O. Abuga2James A. Mbah3Rajshekhar Karpoormath4Dennis Ongarora5Hannington Mugo6Elvis Monya7Fidelis Cho-Ngwa8Wolfgang Sippl9Edric Joel Loveridge10Fidele Ntie-Kang11Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, CameroonInstitute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle, GermanyDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, KenyaDepartment of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, CameroonDepartment of Pharmaceutical Chemistry, School of Chemistry, University of KwaZulu-Natal, Durban 4001, South AfricaDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, KenyaDepartment of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, KenyaANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, CameroonANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, CameroonInstitute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle, GermanyDepartment of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, UKDepartment of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, CameroonA new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (<b>1</b>), along with eight known compounds—voacangine (<b>2</b>), voacristine (<b>3</b>), coronaridine (<b>4</b>), tabernanthine (<b>5</b>), iboxygaine (<b>6</b>), voacamine (<b>7</b>), voacorine (<b>8</b>) and conoduramine (<b>9</b>)—were isolated from the stem bark of <i>Voacangaafricana</i>. The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>4</b>, <b>6</b>, <b>7</b> and <b>8</b> were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of <i>Onchocerca ochengi</i>, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC<sub>50</sub> values of the isolates are 2.49–5.49 µM for microfilariae and 3.45–17.87 µM for adult males. Homology modeling was used to generate a 3D model of the <i>O. ochengi</i> thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal structure–activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of <i>V. africana</i> in the treatment of human onchocerciasis.https://www.mdpi.com/1420-3049/26/1/70alkaloidsanti-onchocercalbisindolesdockinghomology modelingmonoindoles |
| spellingShingle | Smith B. Babiaka Conrad V. Simoben Kennedy O. Abuga James A. Mbah Rajshekhar Karpoormath Dennis Ongarora Hannington Mugo Elvis Monya Fidelis Cho-Ngwa Wolfgang Sippl Edric Joel Loveridge Fidele Ntie-Kang Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling Molecules alkaloids anti-onchocercal bisindoles docking homology modeling monoindoles |
| title | Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling |
| title_full | Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling |
| title_fullStr | Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling |
| title_full_unstemmed | Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling |
| title_short | Alkaloids with Anti-Onchocercal Activity from <i>Voacanga africana</i> Stapf (Apocynaceae): Identification and Molecular Modeling |
| title_sort | alkaloids with anti onchocercal activity from i voacanga africana i stapf apocynaceae identification and molecular modeling |
| topic | alkaloids anti-onchocercal bisindoles docking homology modeling monoindoles |
| url | https://www.mdpi.com/1420-3049/26/1/70 |
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