天然产物拥有巨大的药物发现潜力,然而,在庞大的图书馆和数据库中,许多仍未被开发。为了填补这一空白,满足对有效药物日益增长的需求,这项研究深入研究了有前途的ent-kaurane二萜的世界,一类具有巨大治疗潜力的天然产品。使用从文献中获得的570种ent-kaurane二萜的数据集,我们进行了模拟分析,评估他们的物理化学,药代动力学,和毒理学特性,重点是它们的治疗意义。值得注意的是,这些天然化合物表现出类似药物的特性,与FDA批准的药物密切相关,表明药物开发的潜力很大。物理化学参数的范围如下:分子量288.47至626.82g/mol;重原子数21至44;氢键供体和受体的数量分别为0至8和1至11;可旋转键数-0至11;馏分Csp3-0.65至1;和TPSA-20.23至189.53。此外,这些分子中的大多数显示出良好的安全性,只有0.70%,1.40%,0.70%,46.49%表现出诱变性,致瘤性,生殖增强,和刺激性,分别。重要的是,ent-kaurane二萜化合物表现出有希望的生物制药特性。它们的平均亲脂性是药物吸收的最佳选择,99%以上是水溶性的,促进交付。Further,这些分子中有96.5%和28.20%表现出肠和脑生物利用度,扩大他们的治疗范围。这些化合物的预测药理活性涵盖了不同的范围,包括抗癌,免疫抑制剂,化学防护,抗肝,肝脏保护剂,抗炎,抗甲状腺功能亢进,和抗肝炎活动。这种多目标特征突出了ent-kaurane二萜作为进一步药物发现努力的非常有希望的候选物。
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 ent-kaurane diterpenoids, a class of natural products with huge therapeutic potential. With a dataset of 570 ent-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, ent-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 ent-kaurane diterpenoids as highly promising candidates for further drug discovery endeavors.