头孢他汀和利特瑞嗪代表了迷人的二聚海洋衍生甾体生物碱类,具有独特的化学结构和有希望的生物活性。最初是从日本沿海收集的海洋管虫和被膜Ritterellatokioka中分离出来的,头孢他汀类药物和利特沙嗪通过诱导细胞凋亡显示出有效的抗癌作用,破坏细胞周期进程,靶向多种分子途径。这篇综述涵盖了1988年至2024年45种头孢他汀类药物和利特瑞嗪的化学和生物活性,强调了它们的复杂结构和药用贡献。深入了解它们的结构活动关系(SAR)。关键结构要素,如吡嗪环和5/6螺缩酮部分,被发现对它们的生物效应至关重要,提示与脂质膜或疏水性蛋白质结构域的相互作用。此外,螺缩酮裂解形成氧碳正离子可通过共价修饰DNA来增强其效力。药代动力学,这些甾体生物碱的ADMET和药物相似性特性已得到彻底解决。药物相似性分析表明,这些化合物符合蛋白质-蛋白质相互作用药物(PPID)的规则4(Ro4),强调他们在这一领域的潜力。10种化合物(20、27、33、34、39、40、41、42、43和45)已显示出良好的药代动力学和ADMET曲线,使他们有希望进一步研究的候选人。未来的努力应该集中在替代管理途径上,结构修改,和创新的交付系统,例如前药和纳米颗粒,以提高生物利用度和治疗效果。合成化学的进展,机械论的见解,和跨学科合作对于将头孢他汀类药物和利特瑞嗪转化为有效的抗癌疗法至关重要。
Cephalostatins and ritterazines represent fascinating classes of dimeric marine derived steroidal alkaloids with unique chemical structures and promising biological activities. Originally isolated from marine tube worms and the tunicate Ritterella tokioka collected off the coast of Japan, cephalostatins and ritterazines display potent anticancer effects by inducing apoptosis, disrupting cell cycle progression, and targeting multiple molecular pathways. This review covers the chemistry and bioactivities of 45 cephalostatins and ritterazines from 1988 to 2024, highlighting their complex structures and medicinal contributions. With insights into their structure activity relationships (SAR). Key structural elements, such as the pyrazine ring and 5/6 spiroketal moieties, are found crucial for their biological effects, suggesting interactions with lipid membranes or hydrophobic protein domains. Additionally, the formation of oxocarbenium ions from spiroketal cleavage may enhance their potency by covalently modifying DNA. The pharmacokinetics, ADMET and Drug likeness properties of these steroidal alkaloids are thoroughly addressed. Drug likeness analysis shows that these compounds fit well with the Rule of 4 (Ro4) for Protein-Protein Interaction Drugs (PPIDs), underscoring their potential in this area. Ten compounds (20, 27, 33, 34, 39, 40, 41, 42, 43, and 45) have demonstrated favourable pharmacokinetic and ADMET profiles, making them promising candidates for further research. Future efforts should focus on alternative administration routes, structural modifications, and innovative delivery systems, such as prodrugs and nanoparticles, to improve bioavailability and therapeutic effects. Advances in synthetic chemistry, mechanistic insights, and interdisciplinary collaborations will be essential for translating cephalostatins and ritterazines into effective anticancer therapies.