The triazolopyrimidine ring has emerged as a ubiquitous and highly versatile structural motif found in a wide array of biologically active compounds. Owing to its unique fused heterocyclic architecture, this core is capable of engaging in diverse intermolecular interactions with biological targets. Such features have placed triazolopyrimidines as a particularly attractive scaffold in contemporary anticancer drug discovery. Over the past decade, and more conspicuously in the last five years, this framework has gained substantial attention due to its ability to modulate multiple cancer-relevant pathways with notable potency and selectivity. Strategic structural modifications, such as derivatization with appropriate substituents, hybridization with other pharmacophores, and metal complexation, have significantly enhanced their pharmacological profiles. These rational approaches not only improve efficacy and selectivity but also address key challenges, such as drug resistance, bioavailability, and off-target toxicity. Recent advances have also highlighted the potential of both organic derivatives and inorganic triazolopyrimidine-based complexes, particularly in the context of metallodrugs, where coordination with transition metals has led to improved cytotoxicity and novel mechanisms of action. Collectively, these developments highlight the promise of triazolopyrimidine scaffolds in transforming the current landscape of cancer therapy. This review critically summarizes and discusses the progress made in the design, synthesis, and anticancer evaluation of triazolopyrimidine-based organic and inorganic scaffolds reported in the scientific literature over the past five years, with an emphasis on their mechanisms of action and future therapeutic prospects.
I. Lumb, Jaskirat Singh, Yukta Soni et al.· Mini-Reviews in Medical Chem...· 0 citations
Plastic waste presents a persistent environmental burden, yet its constituent polymers represent structurally valuable chemical feedstocks. Mechanical recycling remains limited due to polymer degradation, additive contamination, and material downcycling, underscoring the need for alternative strategies. Chemical upcycling offers pathways to convert post-consumer plastics into higher-value monomers, functional chemicals, and bioactive or pharmaceutical precursors by exploiting inherent structural motifs such as aromatic rings, ester linkages, and heteroatom-containing backbones. Approaches such as catalytic depolymerization, molecular functionalization, microbial and enzymatic transformation, and scaffold repurposing enable the recovery of polymer-derived building blocks with improved functional value. Case studies illustrating the conversion of discarded plastics into advanced materials and biologically relevant small molecules demonstrate the potential of these approaches to stimulate innovation and expand sustainable chemical practices. Collectively, such developments align with green chemistry principles, support emerging circular chemical economies, and contribute to global sustainability priorities reflected in the United Nations Sustainable Development Goals. This review aims to outline the guiding principles of chemical upcycling and highlight the challenges in chemical design, encouraging the modern chemistry community to tap into the hidden potential of waste plastics.
A library of 4-aminoquinoline derivatives and benzoxaborole-4-aminoquinoline hybrids, linked through amide and 1H-1,2,3-triazole spacers, was synthesized and evaluated against both chloroquine-sensitive (3D7) and -resistant (W2) strains of Plasmodium falciparum. Structure–activity relationship studies revealed that antiplasmodial potency was strongly influenced by the length of the alkyl chain and by the nature of the terminal functional group (azido, aldehyde, or benzyl alcohol). Notably, incorporation of the benzoxaborole core significantly enhanced activity relative to the parent 4-aminoquinoline derivatives. Among the series, hybrid 8b emerged as the most potent analogue, displaying superior activity against the CQ-resistant W2 strain compared with the reference antimalarials quinine and chloroquine. The hybrids exhibited negligible cytotoxicity toward HEK-293 cells, affording selectivity indices of up to ∼700. UV-visible spectroscopic titrations demonstrated that compound 8b binds monomeric heme more selectively than CQ at both physiological and digestive vacuole pH, supporting inhibition of hemozoin formation as its primary mode of action. Furthermore, homology modelling, induced-fit docking, and molecular dynamics simulations with both wild-type and benzoxaborole-resistant (H36Y/D470N) PfCPSF3 suggested that the scaffold can maintain a stable Zn2+-coordinated binding mode in both protein variants. These findings indicate a potential dual mechanism involving hemozoin inhibition and PfCPSF3 targeting, warranting further experimental validation.
Anuradha Saini, Sumit Kumar, B. Pradines et al.· RSC Advances· 0 citations
Overall, the cytotoxic effects of 7k on MV4-11 cells are attributed to the coordinated induction of ROS-mediated oxidative stress, G0/G1 cell cycle arrest, and caspase-dependent apoptosis, highlighting its promising antiproliferative potential.
