Hongzhen Jin

In this study, the total synthesis of osajin, scandenone and their analogues have been accomplished. The key synthetic steps include aldol/intramolecular iodoetherification/elimination sequence reactions and a Suzuki coupling reaction to assemble the tricyclic core, chemoselective propargylation and Claisen rearrangement reactions to obtain natural compounds. In addition, we also designed and synthesized twenty-five natural product analogues. All synthetic compounds were screened for anti-inflammatory activity against tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Collectively, Compound 39e and 39d were considered as promising lead compounds for further development.

Low molecular weight heparins (LMWHs) are derived from heparin through chemical or enzymatic cleavage with an average molecular weight (Mw) of 2000–8000 Da. They exhibit more selective activities and advantages over heparin, causing fewer side effects, such as bleeding and heparin-induced thrombocytopenia. Due to different preparation methods, LMWHs have diverse structures and extensive biological activities. In this review, we describe the basic preparation methods in this field and compare the main principles and advantages of these specific methods in detail. Importantly, we focus on the non-anticoagulant pharmacological effects of LMWHs and their conjugates, such as preventing glycocalyx shedding, anti-inflammatory, antiviral infection, anti-fibrosis, inhibiting angiogenesis, inhibiting cell adhesion and improving endothelial function. LMWHs are effective in various diseases at the animal level, including cancer, some viral diseases, fibrotic diseases, and obstetric diseases. Finally, we briefly summarize their usage and potential applications in the clinic to promote the development and utilization of LMWHs.

The first total synthesis of lineaflavones A, C, D, and their analogues has been accomplished. The key synthetic steps include aldol/oxa-Michael/dehydration sequence reactions to assemble the tricyclic core, Claisen rearrangement and Schenck ene reaction to construct the key intermediate, and selective substitution or elimination of tertiary allylic alcohol to obtain natural compounds. In addition, we also explored five new routes to synthesize fifty-three natural product analogues, which can contribute to a systematic structure–activity relationship during biological evaluation.

Cancer incidence and mortality are rapidly increasing worldwide; therefore, effective therapies are required in the current scenario of increasing cancer cases. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, and they have become the focus of current antitumour drug research owing to their significant antitumour effects. In addition to the direct antitumour activity of some natural polysaccharides, their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in natural polysaccharides and polysaccharide-based nanomedicines for cancer therapy.

Central nervous system (CNS) diseases threaten the health of people all over the world. However, due to the structural and functional particularities of the brain and spinal cord, CNS-targeted drug development is rather challenging. Exosomes are small cellular vesicles with lipid bilayers that can be secreted by almost all cells and play important roles in intercellular communication. The advantages of low immunogenicity, the ability to cross the blood-brain barrier, and the flexibility of drug encapsulation make them stand out among CNS drug delivery tools. Herein, we reviewed the research on exosomes in CNS drug delivery over the past decade and outlined the impact of the drug loading mode, administration route, and engineered modification on CNS targeting. Finally, we highlighted the problems and prospects of exosomes as CNS drug delivery tools.