A Review of the Azasteroid-type 5-alpha Reductase Inhibitors for the Management of Benign Prostatic Hyperplasia

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL Letters in Drug Design & Discovery Pub Date : 2023-10-06 DOI:10.2174/0115701808241219230923154750
Girish Chandra Arya, Ankit Rathee, Rajiv Sharma, Shefali Mehla, Preeti Bisht
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Abstract

Background:: Prostate cancer is one of the most complex cancer and most common in elderly males. The prostate gland's malignant growth known as benign prostatic hyperplasia (BPH) is associated with lower urinary tract symptoms (LUTS) such as frequency hesitancy, and urgency. Various treatment strategies have been employed for management of prostate cancer. Due to its prolonged treatment, varying clinical treatment and high association with treatment related morbidity raise serious questions about the ideal treatment strategy for the patients. Except for skin cancer, prostate cancer is the most frequent cancer among men. Introduction:: Prostate cancer cases were estimated at 14, 14,259 and 3, 75,304 persons were died globally in 2020. It is the fourth most frequent type of cancer to be discovered worldwide. It impacts over 75% of people by the time they turn 65 and its prevalence increases with age. It seems sensible that 5-alpha reductase inhibitors prevent the conversion of testosterone to dihydrotestosterone and would be used to treat benign prostatic hyperplasia because high levels of the 5-alpha reductase enzymes in humans lead to excessive levels of dihydrotestosterone in peripheral tissues. Method:: Finasteride (Proscar) and dutasteride (Avodart) are 5-alpha reductase inhibitors (5-ARIs) used in the treatment of lower urinary tract symptoms (LUTS) with prostatic enlargement as these suppress the androgens. Finasteride in clinical trials shows a 25% reduction in prostate cancer in randomized trials. Dutasteride (Avodart) shows the reduction in risk of prostate cancer by 23 % (approx.) but it also affects the detection of prostate cancer by affecting the levels of prostate-specific antigen. Result:: The structural requirements for potential 5-alpha reductase inhibitors might be revealed via ligand-based comparative pharmacophore research employing the known strong inhibitors. These approaches can generate data can be utilized to create more effective and selective inhibitors that pharmaceutical industries can produce at a lesser price. Conclusion:: 5-alpha reductase inhibitors are useful in the management of prostate cancer. However, further studies are needed to elucidate the optimal utilization, long-term effects and potential risks in prostate cancer treatment. All 5-alpha reductase inhibitor subcategories have been addressed in this review.
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阿扎甾类5- α还原酶抑制剂治疗前列腺增生的研究进展
背景:前列腺癌是最复杂的癌症之一,最常见于老年男性。前列腺的恶性生长被称为良性前列腺增生(BPH)与下尿路症状(LUTS)有关,如频率犹豫和尿急。前列腺癌的治疗策略多种多样。由于其治疗时间长,临床治疗方法多样,且与治疗相关的发病率高,因此对患者的理想治疗策略提出了严重的问题。除皮肤癌外,前列腺癌是男性中最常见的癌症。导读:2020年,全球前列腺癌病例估计为14,14,259例,死亡人数为3,75,304人。它是世界上第四大最常见的癌症类型。到65岁时,超过75%的人会受到影响,其患病率随着年龄的增长而增加。5- α还原酶抑制剂阻止睾酮向双氢睾酮的转化,并将用于治疗良性前列腺增生,这似乎是合理的,因为人体中高水平的5- α还原酶会导致外周组织中过量的双氢睾酮。方法:非那雄胺(Proscar)和度他雄胺(Avodart)是5- α还原酶抑制剂(5-ARIs),用于治疗前列腺肥大的下尿路症状(LUTS),因为它们抑制雄激素。在随机试验中,非那雄胺在临床试验中显示前列腺癌减少25%。杜他雄胺(Avodart)显示前列腺癌风险降低23%(约23%),但它也通过影响前列腺特异性抗原的水平影响前列腺癌的检测。结果:利用已知的强抑制剂,通过基于配体的比较药效团研究,可以揭示潜在的5- α还原酶抑制剂的结构要求。这些方法可以产生数据,可以用来创造更有效和选择性抑制剂,制药工业可以以更低的价格生产。结论:5- α还原酶抑制剂是治疗前列腺癌的有效药物。然而,需要进一步的研究来阐明其在前列腺癌治疗中的最佳利用、长期效果和潜在风险。所有5- α还原酶抑制剂亚类已在本综述中讨论。
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来源期刊
CiteScore
1.80
自引率
10.00%
发文量
245
审稿时长
3 months
期刊介绍: Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
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