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Target-oriented triazole-based hybrid scaffolds in drug discovery: Advances in molecular design, mechanistic insights and structure–activity relationships

Year: 2026

Type: article

Abstract: Triazole-containing heterocycles have emerged as privileged scaffolds in medicinal chemistry owing to their unique electronic properties, metabolic stability and remarkable capacity to engage in diverse non-covalent interactions with biological targets. In recent years, extensive efforts have been directed toward the development of triazole-based hybrids as multifunctional therapeutic agents with applications spanning anti-tubercular, antimicrobial, antifungal, anticancer, neuroprotective and anti-inflammatory drug discovery. This review provides a comprehensive overview of recent advances in the synthesis, biological evaluation, and structure–activity relationship (SAR) of structurally diverse triazole hybrids, including benzothiazole–triazoles, triazole-acetophenone, coumarin–triazoles, pyrazole–triazoles, tacrine–triazoles, and spirooxindole-based systems. Particular emphasis is placed on target-oriented design strategies involving key proteins such as DprE1, CYP121, EGFR, CDK4/6, JNK3, and acetylcholinesterase. Emerging SAR trends reveal that scaffold hybridization, electronic modulation, lipophilic balance, and linker optimization are critical determinants of potency and selectivity. Molecular docking and mechanistic investigations further support the therapeutic potential of these scaffolds. Collectively, this review highlights triazole hybrids as versatile platforms for future drug development and provides insights for rational design of next-generation triazole-based therapeutics.

Source: Next Materials

DOI: 10.1016/j.nxmate.2026.103194