The emergence of multidrug-resistant bacteria emphasizes the urgent need for novel antibacterial compounds targeting unique cellular processes. Two-component signal transduction systems (TCSs) are commonly used by bacteria to couple environmental stimuli to adaptive responses, are absent in mammals, and are embedded in various pathogenic pathways. To attenuate these signaling pathways, we aimed to target the TCS signal transducer histidine kinase (HK) by focusing on their highly conserved adenosine triphosphate-binding domain. We used a structure-based drug design strategy that begins from an inhibitor-bound crystal structure and includes a significant number of structurally simplifiying “intuitive” modifications to arrive at the simple achiral, biaryl target structures. Thus, ligands were designed, leading to a series of thiophene derivatives. These compounds were synthesized and evaluated in vitro against bacterial HKs. We identified eight compounds with significant inhibitory activities against these proteins, two of which exhibited broad-spectrum antimicrobial activity. The compounds were also evaluated as adjuvants for the treatment of resistant bacteria. One compound was found to restore the sensivity of these bacteria to the respective antibiotics.

Bacterial resistance development represents a serious threat to human health across the globe and has become a very serious clinical problem for many classes of antibiotics. Hence, there is a constant and urgent need for the discovery and development of new effective antibacterial agents to stem the emergence of resistant bacteria. 1,4-naphthoquinones are an important class of natural products and have been known for decades as a privileged scaffold in medicinal chemistry regarding their many biological properties. The significant biological properties of specific 1,4-naphthoquinones hydroxyderivatives have drawn the attention of researchers in order to find new derivatives with an optimized activity, mainly as antibacterial agents. Based on juglone, naphthazarin, plumbagin and lawsone moieties, structural optimization was realized with the purpose of improving the antibacterial activity. Thereupon, relevant antibacterial activities have been observed on different panels of bacterial strains including resistant ones. In this review, we highlight the interest of developing new 1,4-naphthoquinones hydroxyderivatives and some metal complexes as promising antibacterial agents alternatives. Here, we thoroughly report for the first time both the antibacterial activity and the chemical synthesis of four different 1,4-naphthoquinones (juglone, naphthazarin, plumbagin and lawsone) from 2002 to 2022 with an emphasis on the structure-activity relationship, when applicable.

Volatile organic compounds (VOCs) with a large chemical diversity are emitted by plant flowers. These compounds play an important role in the ecology of plants. This review presents the different ecological roles of VOCs present in the odor plumes of plant flowers, such as pollination, defense, adaptation to their environment, and communication with other organisms. The production and accumulation sites of VOCs in plants with their spatial and temporal variations, including environmental issues, are also summarized. To evaluate the qualitative and quantitative chemical composition of VOCs, several methods of extraction and analysis were used. Headspace (HS) sampling coupled with solid phase microextraction (SPME) is now well-developed for the extraction process. Parameters are known, and several fibers are now available to optimize this extraction. Most of the time, SPME is coupled with gas chromatography-mass spectrometry (GC-MS) to determine the structural identification of the VOCs, paying attention to the use of several complementary methods for identification like the use of databases, retention indices, and, when available, comparison with authentic standards analyses. The development of the knowledge on VOCs emitted by flowers is of great importance for plant ecology in the context of environmental and climate changes.