Medicinal Research Reviews最新文献

The sulfanilamido skeleton is the core part of many clinical drugs with the para-aminobenzenesulfamido scaffold. Especially as the first type of synthetic antibacterial drugs, sulfanilamides have played important roles in preventing and treating infectious diseases for more than 90 years. Increasing efforts have been contributing toward the sulfanilamido skeleton with the incorporation of various unique substituents through medicinal design, which accessed great achievements that have not only broken the classical structure–activity relationship of antibacterial sulfanilamides, but also extended the other medicinal applications of sulfanilamides except for antibacterial drugs. Recently, the sulfanilamido-based medicinal design and research are becoming increasingly active, which have aroused widespread concern in the medicinal community. Thus, based on our work on sulfanilamido skeleton, this review article encompasses a robust collection of 746 references from 2008 to the present and, for the first time, provides comprehensive insights into sulfanilamido-based medicinal design and research across a wide range of medicinal potential. It is involved in antibacterial, antifungal, antitubercular, antiviral, anticancer, anti-inflammatory, antiglaucoma, antiparasitic, psychotherapeutic, antidiabetic, and other medicinal aspects. It also covers a large amount of sulfanilamido-based rich information on medicinal chemistry, including some important clinical sulfanilamido-based drugs, sulfanilamido-based medicinal molecular design strategies, structure–activity relationships, some important action targets, some important action mechanisms, as well as a multitargeting medicinal design strategy and medicinal chemicobiology. The foreseeable future research directions and trends toward medicinal design and development of sulfanilamido skeleton are prospected. This work might provide beneficial help for sulfanilamido-based rational design and development to afford sulfanilamido-based drugs with broad spectrum, high biological activity, and low toxicity to treat various diseases worldwide.

The increasing prevalence of drug resistance (DR) and pesticide resistance poses a significant threat to public health, necessitating the development of innovative strategies to discover more effective drugs and pesticides. In this context, artificial intelligence (AI) has emerged as a promising solution. This review examines the roles of AI in tackling DR. An analysis of current literature reveals that AI can enhance the drug discovery process, facilitating the faster creation of effective and safer medications. Furthermore, AI is crucial in predicting and elucidating the mechanisms of DR and pesticide resistance. By offering decision support to healthcare providers, AI-driven precision medicine paves the way for personalized treatment options. Moreover, AI aids in identifying synergistic drug combinations essential for combating DR. Lessons from the recent use of AI in addressing DR demonstrate the potential of this versatile tool to offer solutions required for controlling infections and cancers in the era of DR. However, despite the advancements achieved, challenges such as data accessibility and ethical issues remain. This highlights the need for interdisciplinary collaboration and ethical consideration. Finally, we provide an outlook on future actions required to successfully implement AI-powered technologies in drug and pesticide discovery.

Three-dimensional (3D) bioprinting is a promising technology for the fabrication of complex tissue structures with bionic biological functions and stable mechanical properties. Compared to traditional two-dimensional models and animal models, 3D bioprinted biomimetic tissue models offer enhanced mimicry of biological systems, enable high-throughput screening, reduce experimental costs, and have multiple applications in disease modeling, drug discovery, and precision medicine. Despite recent advancements in the commercialization of 3D bioprinting, the technology continues to encounter bioethical and legal issues, as well as a lack of innovation in novel biomaterials. This review provides an overview of the fundamental techniques of 3D bioprinting and examines the benefits of utilizing this technology to develop organoid and organ-on-a-chip (OOC) functional tissue models. Subsequently, the review will highlight the numerous applications of 3D bioprinting in drug discovery, drug screening, and precision therapy. Additionally, the review will also focus on the constraints of existing technology and propose future research directions.

As the most extensively studied photoswitch in photopharmacology, the azobenzene photoswitch has precision instrumental in the photoregulation of physiological processes across various animal models. Currently, it exhibits the greatest clinical potential for photosensitive retinal restoration, capable of inducing long-term therapeutic effects following intravitreal injection, without the need for foreign gene expression or optical fiber implantation. A significant advancement in the application of azobenzene photoswitches is their integration with optical flow control technology, which facilitates the targeting of deep tissues within the mouse cerebral cortex, addressing long-standing challenges related to tissue penetration depth in photopharmacology. With exceptional spatial and temporal resolution, photopharmacology is particularly well-suited for precision medicine, holding substantial potential for further development. Consequently, a comprehensive summary and review of the design strategies of azobenzene photoswitches for In Vivo applications, along with their experimental outcomes, are essential for guiding future advancements in photopharmacology. This review provides an overview of the fundamental properties and design strategies of azobenzene photoswitch molecules. Additionally, we extensively summarize all azobenzene photoswitch molecules successfully applied In Vivo for photopharmacological purposes since 2006, covering species such as Caenorhabditis elegans, Xenopus tadpoles, zebrafish, mice, rats, rabbits, and canines. Finally, we discuss the challenges associated with the In Vivo implementation of azobenzene photoswitch molecules and propose potential solutions.

Semicarbazide-sensitive amine oxidase (SSAO) is a vascular enzyme and expressed in high concentrations in vascular smooth muscle cells (VSMCs), localized in the caveolae of the plasma membrane, and the endothelial cells. SSAO is classified as a copper amine oxidase and encoded by the amine oxidase copper-containing 3 gene. SSAO exists both as a soluble protein and as a tissue-bound transmembrane protein. The latter is often called vascular adhesion protein 1. Vascular adhesion protein-1 or VAP-1, encoded by the AOC3 gene, is a pro-inflammatory and multifunctional molecule belonging to the SSAO family. It assists the transformation of primary amines to aldehydes resulting in the production of hydrogen peroxide and ammonia. Work from the last two decades, has shown that VAP-1/SSAO plays a role in several physiological and pathological processes, making it a potentially valuable target for therapeutic development. In this review, we provide a detailed overview of the inhibitors of VAP-1/SSAO that are being developed specifically for the treatment of inflammatory diseases. Here in we have highlighted important aspects of the compounds investigated in therapeutic applications. Furthermore, we have outlined potential avenues for innovation with the aim of maximizing the therapeutic efficacy of VAP-1/SSAO inhibitors in clinical settings.

Melatonin, N-acetyl-5-methoxytryptamine, is a tryptophan-derived hormone mostly produced in the pineal gland, despite being synthesized locally at several tissues and organs. This production is rhythmically controlled by complex clock gene networks in the master pacemaker located in the suprachiasmatic nucleus of the hypothalamus. Melatonin is usually secreted only during the dark phase of the day and is essential to synchronize circadian rhythms and neuroendocrine physiological processes. Its main clinical use is associated with the treatment of jet lag and other circadian rhythm sleep disorders, with a growing number of other promising therapeutic applications due to the diverse physiological roles of melatonin. In this review, we explore melatonin and its receptors and provide an updated overview on research concerning the role of melatonin, either as an endogenous molecule or as a drug, in: sleep–wake cycle regulation; circadian rhythms; inflammatory processes that may compromise cardiovascular, respiratory, gastrointestinal, renal, and reproductive system functions; and neurodegenerative disorders such as Alzheimer's and Parkinson's disease. The most recent and promising research findings concerning melatonin synthetic analogs such as agomelatine and ramelteon are highlighted, pointing toward new compounds with promising pharmacological activity while emphasizing their structural differences and advantages when compared to melatonin.