Nitric oxide is a crucial gasotransmitter with a diverse range of physiological functions, notably including its significant antimicrobial properties. This review succinctly summarizes its antibacterial mechanisms and current advancements in NO delivery systems pertinent to infection-associated biomedical applications. Furthermore, it explores the challenges associated with NO delivery, emphasizing how computational and machine learning-based approaches can aid in overcoming these limitations by optimizing design and predicting efficacy.

Haouamine A, a structurally unique ascidian diterpenoid isolated from the marine tunicate Aplidium haouarianum, exhibits potent cytotoxicity against HT-29 colon carcinoma cells (IC50 = 0.1 μg/mL). Its unprecedented 3-aza-[7]-paracyclophane core, featuring planar chirality and severe ring strain (14–15.6 kcal/mol), poses significant synthetic challenges due to dynamic isomerism (nitrogen inversion) and a congested quaternary centre. This review chronicles two decades of synthetic campaigns, showcasing a diversity of strategic solutions to the formidable challenges posed by haouamine A’s architecture. Key breakthroughs include Baran’s pyrone-alkyne DielsAlder macrocyclization (8-step racemic synthesis), Fürstner’s asymmetric Heck cascades, and Chen’s strain-accelerated late-stage oxidation. Modular approaches (e.g., Tsukamoto’s Pd-catalyzed "anti-Wacker" cyclization) and biomimetic insights further enriched the synthetic toolbox. Despite these achievements, the biosynthetic origin of haouamine A remains enigmatic, with proposed unconventional tyrosine modifications or unknown enzymatic pathways. Synthetic advances enabled the gram-scale production, configurational assignment (8R,17S,26S), and biological validation of this compound, underscoring its potential as an anticancer scaffold. This work exemplifies how complex natural products drive methodological innovation, offering a paradigm for targeting strained architectures in drug discovery. Future directions include the elucidation of biosynthesis and the development of analogs to optimize bioactivity