School of Pharmacy and Health Sciences

By Ermias Terefe

Dr. Ermias Terefe, Chair of the Pharmacology & Pharmacognosy Department at the School of Pharmacy and Health Sciences has published new research findings on four new anti-HIV compounds from Croton megalocarpus, a widely used medicinal plant in Kenya.

Dr. Terefe assessed the cytotoxicity and anti-HIV activity of Croton megalocarpus, Croton macrostachyus, and Croton dichogamus with the goal of finding potentially effective and safe anti-HIV compounds. His studies were carried out at the USIU-Africa Research Lab, the Kenya Medical Research Institute (KEMRI), the Institute of Primate Research (IPR), and the Royal Botanic Gardens, Kew Green, United Kingdom.

Dr. Terefe’s study discovered four new, previously undescribed anti-HIV compounds, including three eudesmane type diterpenoids: ermiasolide A (5β-Hydroxy-8α-methoxy eudesm-7(11)-en-12, 8-olide), ermiasolide B (5β,8α-Dihydroxy eudesm-7(11)-en-12, 8-olide), ermiasolide C (5β-Hydroxy-8H-β-eudesm-7(11)-en-12,8-olide), and one crotofolane diterpenoid: ermiasoid (1β-acetoxy-3β-chloro-5α,6α-dihydroxycrotocascarin L).

Human immunodeficiency virus (HIV) affects the body’s defense mechanisms and leads to a number of opportunistic infections which later cause fatality as a result of an acquired immunodeficiency syndrome (AIDS). More than half a million individuals have lost their life in 2020 due to this disease.

Antiretroviral drugs have played a great role in improving the quality of life of HIV infected individuals. The side effects of these drugs coupled with resistance of the virus to the various regimens, necessitates the search for potentially new and effective antiretroviral medication.

These newly-discovered compounds displayed the highest anti-HIV activity by inhibiting viral replication with an inhibitory concentration (IC50) value of less than 0.04 µg/mL. Further in vitro assays and computational in-silico studies confirmed that the bioactive compounds work by inhibiting HIV-1 protease enzyme activity. The results of this study will serve as a solid starting point for the development of more potent, safe, and effective HIV medications.

Dr. Terefe's research outputs have been published in prestigious peer-reviewed journals, including Journal of natural products, American chemical society; Molecules, MDPI Basel Switzerland; BMC complementary and alternative therapy, Springer Nature; and Journal of natural products research, Tyler and Francis, and can be read on the links shared below:

1. Terefe, E. M., Okalebo, F. A., Derese, S., Langat, M. K., Mas-Claret, E., Ahmad Q.K., Mariusz J. Muriuki, J. (2022). Anti-HIV Ermiasolides from Croton megalocarpus. Molecules, MDPI (Accepted 12 August 2022)
2. Terefe, E. M., Okalebo, F. A., Derese, S., Muriuki, J., Mas-Claret, E., & Langat, M. K (2022) Anti-HIV crotocascarin ω from Kenyan Croton dichogamus. Journal of Natural products research (Accepted 18 September 2022)
3. Terefe, E. M., Okalebo, F. A., Derese, S., Muriuki, J., Rotich, W., Mas-Claret, E., Sadgrove, N., Padilla-González, G. F., Prescott, T. A. K., Siddique, H., & Langat, M. K. (2022). Constituents of Croton megalocarpus with Potential Anti-HIV Activity. Journal of Natural Products. https://doi.org/10.1021/ACS.JNATPROD.1C01013
4. Terefe, E. M., Okalebo, F. A., Derese, S., Langat, M. K., Mas-Claret, E., Aljarba, N. H., Alkahtani, S., Batiha, G. E.-S., Ghosh, A., El-Masry, E. A., & Muriuki, J. (2022). In vitro anti-HIV and cytotoxic effects of pure compounds isolated from Croton macrostachyus Hochst. Ex Delile. BMC Complementary Medicine and Therapies 2022 22:1, 22(1), 1–10. https://doi.org/10.1186/S12906-022-03638-6
5. Terefe E. M., Okalebo F. A., Deresse S., Muriuki J., Amuhaya E. K., Munyendo L. W., Janapati Y., Obila J., Mosweta J. (2022). Cytotoxicity and antiretroviral activity of the leaf and stem bark extracts of Croton macrostachyus. Pharmaceutical Journal of Kenya, 26(1), 2022. https://psk.or.ke/journals/article-98
6. Terefe, E. M., Okalebo, F. A., Derese, S., Batiha, G. E.-S., Youssef, A., Alorabi, M., & Muriuki, J. (2022). Cytotoxicity and anti-HIV activities of extracts of the twigs of Croton dichogamus Pax. BMC Complementary Medicine and Therapies 2022 22:1, 22(1), 1–8. https://doi.org/10.1186/S12906-022-03532-1 https://pubmed.ncbi.nlm.nih.gov/35216601/
7. Terefe, E. M.; Okalebo, F. A.; Derese, S.; Muriuki, J.; Batiha, G. E.-S. In Vitro Cytotoxicity and Anti-HIV Activity of Crude Extracts of Croton Macrostachyus, Croton Megalocarpus and Croton Dichogamus. J. Exp. Pharmacol. 2021, 13, 971–979. https://doi.org/10.2147/JEP.S335104 https://pubmed.ncbi.nlm.nih.gov/35221732/

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