Structure modification, antialgal, antiplasmodial, and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives.
Structure modification, antialgal, antiplasmodial, and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives.
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DOI：
10.1007/s42995-021-00103-0
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发表时间：
2022-02
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
海洋天然产物在许多海洋生物的化学防御中发挥着关键作用，是成功药物先导的重要、信誉良好的来源。从海洋真菌Cochliobolus luatus中分离得到的天然产物玉米烯醇(1)的67个14元间苯二酸内酯衍生物3-27和30-71经氯化、酰化、酯化、缩醛等一至三步半合成。通过HRESIMS和核磁共振技术确证了这些新化合物的结构。对所有化合物(1-71)的抗藻活性和抗疟原虫活性进行了评价。其中，14个化合物具有抗污垢硅藻附着的活性。其中9号和34号对硅藻有较强的选择性抑制作用(EC_(50) = 分别为6.67和8.55μ/L)，与阳性对照菌株Sea9 211(EC_(50) = 分别为2.90和9.74μm ol/L)相近。更重要的是，38、39和69-71对恶性疟原虫具有较强的抗疟活性，其IC50值在3.5 4~9.72nMol/L之间。有趣的是，这5个抗疟原虫衍生物在细胞毒性试验和斑马鱼胚胎模型中表现出无毒性，是潜在的抗疟药物。初步的构效关系表明，C-2位的联苯取代基、C-5‘和C-6’位的丙酮以及酰基的三取代或四取代可提高抗疟原虫活性。因此，将化学生态评价与药理模型相结合将作为一项系统的战略实施，不仅适用于环境友好型防污剂，也适用于结构新颖的药物。网上版载有补充材料，可在10.1007/s42995-021-00103-0查阅。
Marine natural products play critical roles in the chemical defense of many marine organisms and are essential, reputable sources of successful drug leads. Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol (1) isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination, acylation, esterification, and acetalization in one to three steps. The structures of these new derivatives were established by HRESIMS and NMR techniques. All the compounds (1–71) were evaluated for their antialgal and antiplasmodial activities. Among them, 14 compounds displayed antifouling activities against adhesion of the fouling diatoms. In particular, 9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua (EC50 = 6.67 and 8.55 μmol/L), respectively, which were similar in efficacy to those of the positive control SeaNine 211 (EC50 = 2.90 and 9.74 μmol/L). More importantly, 38, 39, and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72 μmol/L. Very interestingly, the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model, thus, representing potential promising antiplasmodial drug agents. The preliminary structure–activity relationships indicated that biphenyl substituent at C-2, acetonide at positions C-5′ and C-6′, and tri- or tetra-substituted of acyl groups increased the antiplasmodial activity. Therefore, combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy, not only for environmentally friendly antifoulants but also for structurally novel drugs. The online version contains supplementary material available at 10.1007/s42995-021-00103-0.
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DOI：
10.4269/ajtmh.2004.70.119
发表时间：
2004-02-01
影响因子：
3.3
作者：
Corbett, Y;Herrera, L;Ortega-Barria, E
通讯作者：
Ortega-Barria, E
影响因子：
2.1
作者：
Kadari, Sudhakar;Yerrabelly, Hemasri;Doda, Sai Reddy
通讯作者：
Doda, Sai Reddy
影响因子：
82.9
作者：
Miller LH;Ackerman HC;Su XZ;Wellems TE
通讯作者：
Wellems TE
影响因子：
5.2
作者：
Mallampudi, N. Arjunreddy;Srinivas, Beduru;Mohapatra, Debendra K.
通讯作者：
Mohapatra, Debendra K.
影响因子：
1.3
作者：
LAMBROS, C;VANDERBERG, JP
通讯作者：
VANDERBERG, JP