The occurrence of increased antibiotic resistance has reduced the availability of drugs effective in the control of infectious diseases, especially those caused by various combinations of bacteria and/or fungi that are often associated with poorer patient outcomes. In the hunt for novel antibiotics of interest to treat polymicrobial diseases, molecules bearing guanidine moieties have recently come to the fore in designing and optimizing antimicrobial agents. Due to their remarkable antibacterial and antifungal activities, labdane diterpenes are also attracting increasing interest in antimicrobial drug discovery. In this study, six different guanidines prenylated with labdanic fragments were synthesized and evaluated for their antimicrobial properties. Assays were carried out against both non-resistant and antibiotic-resistant bacteria strains, while their possible antifungal activities have been tested on the yeast Candida albicans. Two of the synthesized compounds, namely labdan-8,13(R)-epoxy-15-oyl guanidine and labdan-8,13(S)-epoxy-15-oyl guanidine, were finally selected as the best candidates for further developments in drug discovery, due to their antimicrobial effects on both Gram-negative and Gram-positive bacterial strains, their fungicide action, and their moderate toxicity in vivo on zebrafish embryos. The study also provides insights into the structure-activity relationships of the guanidine-functionalized labdane-type diterpenoids.

抗生素耐药性的增加减少了有效控制传染病的药物的可用性，特别是那些由细菌和/或真菌的各种组合引起的疾病，这些疾病通常与较差的患者预后相关。在寻找治疗多种微生物疾病的新型抗生素的过程中，带有胍部分的分子最近在设计和优化抗菌剂方面脱颖而出。由于其显着的抗菌和抗真菌活性，拉丹丹二萜也引起了抗菌药物发现越来越多的兴趣。在这项研究中，合成了六种不同的用劳丹尼片段异戊二烯化的胍，并评估了它们的抗菌特性。对非耐药和抗生素耐药细菌菌株进行了测定，同时在白色念珠菌上测试了它们可能的抗真菌活性。合成的两种化合物，即 Labdan-8,13( R )-epoxy-15-oyl guanidine 和 Labdan-8,13( S )-epoxy-15-oyl guanidine，最终被选为进一步开发的最佳候选化合物。药物发现，由于它们对革兰氏阴性和革兰氏阳性细菌菌株的抗菌作用、杀菌作用以及对斑马鱼胚胎的体内中等毒性。该研究还深入了解了胍官能化拉丹烷型二萜类化合物的结构-活性关系。