Oliveira Larissa V F, Tempone Andre G, Christodoulides Myron, Lago Joao Henrique G
Center of Natural Sciences and Humanities, Federal University of ABC, Sao Paulo 09210-580, Brazil.
Neisseria Research Laboratory, Molecular Microbiology, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
Molecules. 2025 May 30;30(11):2406. doi: 10.3390/molecules30112406.
Increasing multidrug resistance in poses a serious and escalating public health crisis. The World Health Organization has classified as a high-priority pathogen for developing new antimicrobials. Natural products provide a promising avenue for antimicrobial discovery, serving as direct therapeutic agents or prototypes for novel drug development. Among these, gibbilimbol B, a compound isolated from , is particularly attractive due to its biological potential and simple structure. In this study, eight synthetic phenylalkylamides (-) inspired by gibbilimbol B were synthesized and evaluated for their antibacterial activity against . The in vitro bacterial assays revealed that these compounds exhibit notable antibacterial activity, including against resistant strains selected from the CDC/FDA antimicrobial panel (strains AR-173, AR-174, AR-187, and AR-200). All synthesized compounds demonstrated superior efficacy in killing compared to gibbilimbol B. Notably, compound [()-4-chloro--(oct-4-en-1-yl)benzamide] showed an MBC50 of 6.25 µM, representing a four-fold improvement in bactericidal activity over the natural compound. This study represents the first exploration of gibbilimbol analogs for antibacterial applications, highlighting the novelty of the work and paving the way for the development of new antibacterial agents.
日益增加的多重耐药性构成了一场严重且不断升级的公共卫生危机。世界卫生组织已将其列为开发新型抗菌药物的高优先级病原体。天然产物为抗菌药物的发现提供了一条有前景的途径，可作为直接治疗剂或新型药物开发的原型。其中，从[具体来源未提及]中分离出的化合物吉比林波尔B，因其生物潜力和简单结构而特别具有吸引力。在本研究中，合成了八种受吉比林波尔B启发的合成苯烷基酰胺（-），并评估了它们对[具体细菌未提及]的抗菌活性。体外细菌试验表明，这些化合物表现出显著的抗菌活性，包括对从疾病控制与预防中心/美国食品药品监督管理局抗菌药物筛选小组中选出的耐药菌株（菌株AR - 173、AR - 174、AR - 187和AR - 200）。与吉比林波尔B相比，所有合成化合物在杀死[具体细菌未提及]方面都表现出更高的效力。值得注意的是，化合物[（-）-4-氯-（辛-4-烯-1-基）苯甲酰胺]的MBC50为6.25 µM，其杀菌活性比天然化合物提高了四倍。这项研究代表了对吉比林波尔类似物抗菌应用的首次探索，突出了该工作的新颖性，并为新型抗菌剂的开发铺平了道路。
