Kibet Shadrack, Kimani Njogu M, Mwanza Syombua S, Mudalungu Cynthia M, Santos Cleydson B R, Tanga Chrysantus M
Department of Physical Sciences, University of Embu, Embu P.O. Box 6-60100, Kenya.
International Centre of Insects Physiology and Ecology, Nairobi P.O. Box 30772-00100, Kenya.
Pharmaceuticals (Basel). 2024 Apr 16;17(4):510. doi: 10.3390/ph17040510.
Natural products hold immense potential for drug discovery, yet many remain unexplored in vast libraries and databases. In an attempt to fill this gap and meet the growing demand for effective drugs, this study delves into the promising world of -kaurane diterpenoids, a class of natural products with huge therapeutic potential. With a dataset of 570 -kaurane diterpenoids obtained from the literature, we conducted an in silico analysis, evaluating their physicochemical, pharmacokinetic, and toxicological properties with a focus on their therapeutic implications. Notably, these natural compounds exhibit drug-like properties, aligning closely with those of FDA-approved drugs, indicating a high potential for drug development. The ranges of the physicochemical parameters were as follows: molecular weights-288.47 to 626.82 g/mol; number of heavy atoms-21 to 44; the number of hydrogen bond donors and acceptors-0 to 8 and 1 to 11, respectively; the number of rotatable bonds-0 to 11; fraction Csp3-0.65 to 1; and TPSA-20.23 to 189.53 Ų. Additionally, the majority of these molecules display favorable safety profiles, with only 0.70%, 1.40%, 0.70%, and 46.49% exhibiting mutagenic, tumorigenic, reproduction-enhancing, and irritant properties, respectively. Importantly, -kaurane diterpenoids exhibit promising biopharmaceutical properties. Their average lipophilicity is optimal for drug absorption, while over 99% are water-soluble, facilitating delivery. Further, 96.5% and 28.20% of these molecules exhibited intestinal and brain bioavailability, expanding their therapeutic reach. The predicted pharmacological activities of these compounds encompass a diverse range, including anticancer, immunosuppressant, chemoprotective, anti-hepatic, hepatoprotectant, anti-inflammation, antihyperthyroidism, and anti-hepatitis activities. This multi-targeted profile highlights -kaurane diterpenoids as highly promising candidates for further drug discovery endeavors.
天然产物在药物发现方面具有巨大潜力，但在大量的文库和数据库中，仍有许多未被探索。为了填补这一空白并满足对有效药物日益增长的需求，本研究深入探究了具有巨大治疗潜力的贝壳杉烷二萜类天然产物的广阔领域。我们从文献中获取了一个包含570种贝壳杉烷二萜类化合物的数据集，并进行了计算机模拟分析，重点评估它们的物理化学、药代动力学和毒理学性质及其治疗意义。值得注意的是，这些天然化合物具有类似药物的性质，与FDA批准的药物性质密切相符，表明其具有很高的药物开发潜力。物理化学参数范围如下：分子量为288.47至626.82 g/mol；重原子数为21至44；氢键供体和受体的数量分别为0至8和1至11；可旋转键的数量为0至11；Csp3分数为0.65至1；以及拓扑极性表面积为20.23至189.53 Ų。此外，这些分子中的大多数显示出良好的安全性，分别只有0.70%、1.40%、0.70%和46.49%的分子表现出致突变、致癌、增强生殖和刺激特性。重要的是，贝壳杉烷二萜类化合物具有良好的生物制药性质。它们的平均亲脂性对于药物吸收是最佳的，同时超过99%是水溶性的，便于递送。此外，这些分子中有96.5%和28.20%表现出肠道和脑生物利用度，扩大了它们的治疗范围。这些化合物预测的药理活性涵盖了广泛的范围，包括抗癌、免疫抑制、化学保护、抗肝、保肝、抗炎、抗甲状腺功能亢进和抗肝炎活性。这种多靶点特性突出了贝壳杉烷二萜类化合物作为进一步药物发现努力中极具潜力的候选药物。
