Wekesa Emily N, Kimani Njogu M, Kituyi Sarah N, Omosa Leonidah K, Santos Cleydson B R
Department of Physical Sciences, University of Embu, Kenya.
Department of Biological Sciences, University of Embu, Kenya.
S Afr J Bot. 2023 Nov;162:129-141. doi: 10.1016/j.sajb.2023.09.009. Epub 2023 Sep 14.
Natural products (NPs) are essential in the search for new drugs to treat a wide range of diseases, including infectious and malignant disorders. However, despite the discovery of many bioactive NPs, they often do not make it to market as drugs due to toxicity and other challenges. The development of NPs into drugs is a long and expensive process, and many promising compounds are abandoned along the way. These molecules require ADMET profiling in order to speed up their development into drugs lower costs, and the high attrition rate. The objective of this work was to produce thorough ADMET profiles of secondary metabolites from several classes that were isolated from species. The genus has a long history of therapeutic use, including treating tumours, hypertension, gonorrhoea, coughs, bilharzia, chest pains, and toothaches. The study used a dataset of 406 compounds from the genus for theoretical ADMET analysis. The findings revealed that 81% of the compounds met Lipinski's rule of five, indicating good oral bioavailability. The drug-likeness criteria were taken into account, with percentages ranging from 66.2 to 88.1 percent. Additionally, 9.2% of the compounds were predicted to be lead-like, demonstrating their potential as promising drug development candidates. Interestingly, none of the compounds inhibited hERG I, while 33% inhibited hERG II, potentially having cardiac implications. Additionally, 30% of the compounds exhibited AMES toxicity inhibition, while 23.6% were identified as hepatotoxic and 22.2% would cause skin sensitivity. Moreover, 81.8% of the compounds demonstrated high intestinal absorption, making them desirable for oral drugs. In conclusion, these findings highlight the diverse properties of the investigated compounds and their potential for drug development.
天然产物在寻找治疗多种疾病（包括传染病和恶性疾病）的新药方面至关重要。然而，尽管发现了许多具有生物活性的天然产物，但由于毒性和其他挑战，它们往往无法作为药物上市。将天然产物开发成药物是一个漫长而昂贵的过程，许多有前景的化合物在此过程中被放弃。这些分子需要进行ADMET分析，以加快其开发成药物的速度，降低成本，并减少高淘汰率。这项工作的目的是对从几种物种中分离出的几类次生代谢产物进行全面的ADMET分析。该属具有悠久的治疗应用历史，包括治疗肿瘤、高血压、淋病、咳嗽、血吸虫病、胸痛和牙痛。该研究使用了该属406种化合物的数据集进行理论ADMET分析。研究结果显示，81%的化合物符合Lipinski的五规则，表明其具有良好的口服生物利用度。考虑了类药标准，百分比范围为66.2%至88.1%。此外，9.2%的化合物被预测为类先导物，表明它们作为有前景的药物开发候选物的潜力。有趣的是，没有一种化合物抑制hERG I，而33%的化合物抑制hERG II，这可能对心脏有影响。此外，30%的化合物表现出AMES毒性抑制，23.6%被确定为肝毒性，22.2%会引起皮肤敏感性。此外，81.8%的化合物表现出高肠道吸收，使其适合作为口服药物。总之，这些发现突出了所研究化合物的多样性质及其药物开发潜力。
