Searching for the Holy Grail − Highly Potent Bridged Endoperoxides for Targeted Cancer Therapy

[Display omitted] The International Agency for Research on Cancer (IARC) recently estimated the global cancer burden in 2050. The statistics are startling, with a 77% hike and 35 million new cancer cases per year. The present discoveries have recommended plant-derived bridged endoperoxides or artemisinin-based semisynthetic analogues as safe, well-tolerated and powerful substitutes that could be effectively utilized as a warhead to fight against global enemies like cancer. In addition, artemisinin-based drug repositioning crucially can reduce overriding drug development expenditures and establish accessibility of approved drugs with low risk to patients. Hence, the present review article provides a comprehensive account of the recent chemical and synthetic advancement of diverse cytotoxic artemisinin derivatives such as C(10)–O, C, N, S linked artemisinin analogues, artemisinin-derived metal complexes, artemisinin-derived hybrids/conjugates with other pharmaceutically active substances, and artemisinin-derived dimers, trimers and tetramers perceived during the last three decades (1997–2024). Moreover, the current preclinical and clinical anticancer application prospects of artemisinin derivatives with other defined drugs and their utilization in combination therapy and also nanoformulation approaches for targeted drug delivery have been discussed.