Marine natural products (MNPs) have become new strong leads for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein we report the bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: anilines 1, benzylamines 2, tertiary amines 3 and 4, and quaternary amine salt 5, along with three known compounds (6-8) were isolated from a crude extract and MeOH eluent marine extracts. The absolute configurations of the new compounds were assigned based on tandem mass spectrometry (MS) analysis. Several of the compounds exhibited potent in-vitro antibacterial activity, especially against Methicillin-resistant Staphylococcus aureus (MRSA) (MICs from 15.6 to 62.5 micro g/mL). Herein, we also, report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure activity relationships (SARs) results clearly demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity towards different biological activity. Several commercially available compounds, which are structurally related to the molecules we discovered showed broad spectrum antimicrobial activity against different test pathogens with an MIC50 range of 50 to 0.01 micro M. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential lead molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds with increased bioactivity

中文翻译：

---

从海洋微生物中鉴定生物活性化合物并探索结构活性关系

海洋天然产物（MNP）已成为发现抗菌药物的新的强大线索，并且是控制耐药性感染的有效替代方法。在此，我们报告了从海绵Lendenfeldia，Ircinia和Dysidea提取的海洋提取物的生物测定指导分离，这使我们鉴定了具有抗菌特性的新型化合物。从粗提取物和MeOH洗脱海洋提取物中分离出叔胺或季胺盐：苯胺1，苄胺2，叔胺3和4和季胺盐5以及三种已知化合物（6-8）。基于串联质谱（MS）分析指定了新化合物的绝对构型。这些化合物中的几种显示出有效的体外抗菌活性，尤其是对耐甲氧西林的金黄色葡萄球菌（MRSA）（MIC为15.6至62）。5微克/毫升）。在此，我们还报告了各种商业上结构相似的化合物的结构活性关系。结构活性关系（SARs）结果清楚地表明，通过线性链长对胺的修饰以及芳环的引入修饰了观察到的针对不同生物活性的抗菌活性。与我们发现的分子在结构上相关的几种市售化合物对MIC50范围为50至0.01 micro M的不同测试病原体具有广谱抗菌活性。交叉引用抗菌活性和细胞毒性的结果表明，这些化合物很有希望潜在的铅分子，具有对抗菌药物开发有利的治疗指数。另外，