Feed

Leukemia represents a heterogeneous and refractory hematological malignancy, with current clinical therapies, including conventional chemotherapy, targeted therapy, and hematopoietic stem cell transplantation, still limited by drug resistance, off-target toxicity, and poor efficacy against high-risk subtypes. Indole/azaindole is a privileged heterocyclic scaffold in medicinal chemistry with versatile structural modification potential and inherent antileukemic bioactivity. Rational hybridization of indole/azaindole with diverse pharmacophores has become a core strategy for developing novel antileukemic agents, thereby enabling synergistic efficacy, reversal of drug resistance, and reduced toxicity. This review systematically summarizes the research progress of indole-based hybrids and closely related indole bioisosteres (azaindole hybrids) with antileukemic activity from 2021 to the present. Distinct from previous descriptive reviews, we stratified all candidate compounds by evidence hierarchy: in vitro antiproliferative activity, molecular mechanistic validation, and in vivo preclinical efficacy. This work focuses on structure-activity relationships (SARs), multi-target mechanisms, and preclinical pharmacological characteristics of indole- and azaindole-based antileukemic hybrids, aiming to provide targeted guidance for the rational design and clinical translation of novel indole- and azaindole-based antileukemic drugs.