AYENI, TIMOTHY OLUWATIMILEYIN and Covenant University, Theses Masters (2024) ANDROGEN LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS AND IN SILICO SCREENING OF POTENTIAL INHIBITORS OF SRD5A2 ENZYME. Masters thesis, Covenant University.
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Abstract
Globally, cancer has been recognized as the second most common disease occurring in various organs of the body. Prostate cancer (PC) is among the most prevalent cancer types. It is reportedly the most common form of male cancer in men of African descent, having the highest susceptibility rate. Androgens, such as testosterone and dihydrotestosterone (DHT), are among several risk factors associated with PC risk and progression. They have been well-established to have an essential role in PC development, even at advanced stages. Dihydrotestosterone (DHT), a more active androgen, has been linked to PC development and progression due to its ability to bind the androgen receptor (AR) and initiate its signalling. The steroid 5-alphareductase type-2 (SRD5A2) enzyme, which transforms testosterone into DHT, has been targeted in hormonal therapy for PC using finasteride. However, side effects, including sexual dysfunction, osteoporosis, and cardiovascular diseases, have been associated with the treatment, thereby indicating a need for novel and safer SRD5A2 inhibitors. This study was aimed at determining the levels of circulating androgens (Testosterone and DHT) among Nigerian prostate cancer patients and identify potential drug targets against these androgens. Testosterone and DHT levels were determined using an ELISA assay. A systematic review was performed to identify previously reported plants as SRD5A2 inhibitors, including their phytoconstituents. Thirty-four phytoconstituents from nine medicinal plants were selected and evaluated alongside the standard SRD5A2 inhibitor (finasteride) by employing in silico techniques, including molecular docking, pharmacokinetic prediction, and toxicity profiling. Among the bioactive compounds evaluated, gamma-oryzanol showed the highest binding affinity with SRD5A2 with a binding energy of -11.6 Kcal/mol comparable to the finasteride. Its pharmacokinetics and toxicity profiles were also predicted to be better than finasteride, suggesting its therapeutic potential in drug development for PC treatment. However, further studies should be conducted on gamma-oryzanol to ascertain its toxicity compared to finasteride. We also recommend that additional studies be carried out to evaluate the expression of the SRD5A2 gene in Nigerian PC patients, as this would help establish a personalized treatment for this population.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Androgens, drug target, natural compounds, prostate cancer, SRD5A2 inhibitors |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine |
| Divisions: | Faculty of Engineering, Science and Mathematics > School of Chemistry Faculty of Medicine, Health and Life Sciences > School of Biological Sciences |
| Depositing User: | nwokealisi |
| Date Deposited: | 24 Sep 2024 11:17 |
| Last Modified: | 24 Sep 2024 11:17 |
| URI: | http://eprints.covenantuniversity.edu.ng/id/eprint/18432 |
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