Indole–Pyrazoline Hybrid Derivatives as Potential PARP-1 Targeted Anticancer Agents: A Comprehensive Review of Design Strategies, Structure–Activity Relationships, and Future Perspectives

Poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a clinically validated anticancer target, particularly in tumours harbouring homologous recombination deficiencies [1,2]. Concurrently, molecular hybridisation of the privileged indole and pyrazoline scaffolds has produced a versatile class of anticancer agents with reported activity against tubulin and topoisomerase II, while some derivatives have been investigated for possible EGFR engagement [3–6]. Although the pyrazoline and pyrazole rings share some structural features with the indazole core found in certain PARP-1 inhibitors, experimental evaluation of true indole–pyrazoline hybrids as PARP-1 inhibitors remains limited [7]. This review systematically examines (i) the biological rationale for PARP-1 inhibition, (ii) structure–activity relationship (SAR) lessons from pyrazole- and indazole-based PARP-1 inhibitors, (iii) the existing anticancer profile of indole–pyrazoline hybrids across non-PARP targets, (iv) synthetic accessibility of the hybrid scaffold, and (v) rational design principles that could guide the development of next-generation indole–pyrazoline derivatives for possible PARP-1 engagement. Emphasis is placed on distinguishing experimentally validated findings from docking-based hypotheses, and on identifying concrete opportunities for further experimental investigation.