Betulinic acid derivatives as anticancer agents: Structure activity relationship
Betulinic acid derivatives as anticancer agents: Structure activity relationship
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DOI：
10.2174/187152006776930846
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发表时间：
2006-05-01
影响因子：
2.8
通讯作者：
Burman, Arland C.
中科院分区：
文献类型：
--
作者：
Mukherjee, Rama;Kumar, Vivek;Burman, Arland C.
桦木酸是一种五环三萜，广泛分布于整个热带地区。它具有抗癌、抗炎、抗病毒、抗菌、抗疟疾、杀精子、抗微生物、抗疟疾、抗蠕虫和拒食等多种生物学特性。然而，桦木酸因其抗癌和抗HIV活性而受到高度重视。桦木酸的抗癌作用是通过诱导细胞凋亡而出现的，而与细胞的p53状态无关。由于桦木酸的高度安全性，进行了许多结构修饰以提高其效力和功效。桦木酸的C-1、C-2、C-3、C-4、C-20和C-28位置是桦木酸的多样性中心，并且在这些位置处的各种结构修饰导致的衍生物筛选了它们的抗癌活性。本文综述了白桦酸C-1、C-2、C-3、C-4、C-20、C-28、A环、D环和E环修饰衍生物的构效关系。我们已经编制了最活跃的桦木酸衍生物沿着与他们的活动概况在每个系列。构效关系研究表明，C-28羧酸是细胞毒性所必需的。桦木酸C-2位的卤代取代基增强了细胞毒性。虽然C3位取代基的性质与细胞毒性的关系不能一概而论，但酯官能团似乎是增强细胞毒性的较好取代基。一个有趣的发现是，三环骨架（A，B和C环）在引发抗癌活性中起重要作用，这可能是设计新的抗癌药物的新的分子骨架。
Betulinic acid, a pentacyclic triterpene, is widely distributed throughout the tropics. It possesses several biological properties such as anticancer, anti-inflammatory, antiviral, antiseptic, antimalarial, spermicidal, antimicrobial, antileshmanial, antihelmentic and antifeedent activities. However, betulinic acid was highly regarded for its anticancer and anti-HIV activities. Anticancer role of betulinic acid appeared by inducing apoptosis in cells irrespective of their p53 status. Due to high order safety in betulinic acid, a number of structural modifications carried out to improve its potency and efficacy. The C-1, C-2, C-3, C-4, C-20 and C-28 positions are the diversity centers in betulinic acid, and the derivatives resulted on various structural modifications at these positions screened for their anticancer activity. This review presents the structure activity relationship carried out on C-1, C-2, C-3, C-4, C-20, C-28, A-ring, D-ring and E-ring modified betulinic acid derivatives. We have compiled the most active betulinic acid derivatives along with their activity profile in each series. Structure activity relationship studies revealed that C-28 carboxylic acid was essential for the cytotoxicity. The halo substituent at C-2 position in betulinic acid enhanced the cytotoxicity. Though the relation of the cytotoxicity with the nature of substituents at C-3 position could not be generalized but the ester functionality appeared to be a better substituent for enhancing the cytotoxicity. An interesting observation is that the three rings skeleton (A, B and C rings) had played an important role in eliciting anticancer activity, which could be a new molecular skeleton to design new anticancer drugs.