Quinone‐Based Metal Complexes for Breast Cancer Therapy: Recent Trends in Drug Design and Selectivity

Quinoline-Based Scaffolds in Anticancer Drug Discovery: Molecular Targets, Synthetic Strategies, and Biological Advances.

Cancer remains a major global health challenge, and the limited efficacy, systemic toxicity, multidrug resistance, and tumor recurrence associated with current therapies continue to drive the development of novel targeted anticancer agents. Quinoline-based heterocyclic scaffolds have emerged as valuable structural frameworks in anticancer drug discovery owing to their structural diversity and ability to interact with multiple oncogenic targets. This review provides a target-oriented overview of quinoline-based anticancer agents reported between 2019 and 2025, covering quinoline, quinazoline, quinoxaline, and a few selected nonquinoline nitrogen-containing heterocyclic derivatives. Recent advances in quinoline-based derivatives targeting ER, CDK4/6, topoisomerase I/II, epidermal growth factor receptor, PLCγ1, PI3K/AKT, and VEGFR-2/P-glycoprotein pathways are discussed with respect to their synthetic strategies, in vitro anticancer assay, and structure-activity relationships (SAR). This review integrates comparative SAR trends across diverse quinoline-based scaffolds, highlighting the influence of scaffold planarity, ring fusion, substitution patterns, linker architecture, and metal complexation on anticancer activity. In addition, clinically approved quinoline-based anticancer drugs, representative patents, and future perspectives are summarized to emphasize the translational potential of these scaffolds. Collectively, this review provides a comprehensive overview of recent advances to guide the rational design of next-generation quinoline-based anticancer agents.

Indole-based derivatives as anticancer agents: recent advances in structure–activity relationships and biological mechanisms

Chemical Scaffolds Driving Modern Anticancer Drug Discovery and Radiotheranostics: Structural Determinants, Translational Opportunities and Future Perspectives

Cancer remains one of the leading causes of morbidity and mortality worldwide despite advances in molecular oncology and targeted therapeutics. The growing demand for precision medicine has accelerated the development of radiotheranostics, an emerging paradigm that integrates molecular imaging and targeted radionuclide therapy. In parallel, medicinal chemistry continues to generate structurally diverse small-molecule scaffolds capable of modulating key oncogenic pathways. Increasing evidence indicates that certain chemical scaffolds possess intrinsic properties that extend beyond conventional anticancer activity and support their translation into radiotheranostic applications. This review examines major scaffold classes driving contemporary anticancer drug discovery, including thiosemicarbazones, heterocyclic compounds, metal-based agents, hybrid molecules, and multifunctional platforms. Particular attention is given to the structural features governing biological activity, target selectivity, metal coordination, and radiolabeling potential. The review further highlights the mechanistic convergence between scaffold-mediated anticancer effects and radionuclide-induced cytotoxicity, emphasizing shared pathways involving DNA damage, oxidative stress, inhibition of DNA repair, and modulation of oncogenic signaling. Based on these observations, a scaffold-centered framework for radiotheranostic development is proposed, with perspectives on hybrid molecular design, copper-based theranostic systems, and artificial intelligence-assisted ligand discovery. By integrating medicinal chemistry, molecular oncology, and nuclear medicine, this review outlines structural principles that may facilitate the rational design of next-generation precision anticancer agents and radiotheranostic platforms.

Isatin Derivatives as Emerging Frontiers in Cancer Treatment: Recent Updates in Synthesis, Anticancer Effect, and SAR Studies

Due to its extensive biological activity and structural heterogeneity, the special nitrogen‐containing heterocyclic compound isatin (1 H ‐indole‐2,3‐dione) has attracted significant interest. This paper explains the synthesis and action of heterocyclic isatin hybrids that induce apoptosis by blocking kinases, serving as an appropriate model for the development of new anticancer drugs. Isatin has significant potential to form potent isatin hybrids and conjugates that target multiple carcinogenic pathways through various chemical modifications. Remarkably, isatin hybrids have demonstrated anticancer activity across numerous cancer cell lines. Their activities include inhibition of tubulin polymerization, caspase activation, apoptosis mediated by mitochondria, and regulation of kinases. Several synthetic isatin‐based drugs show excellent IC 50 values and low toxicity against normal cells. This review also summarizes recent synthetic advancements like microwave‐assisted and multi‐component methods. In addition to summarizing recent advances, this review critically integrates SAR, molecular docking, kinase selectivity, synthetic feasibility, CADD, predictive ADMET profiling, and translational challenges to afford a complete roadmap for isatin‐based anticancer drug discovery. Overall, these findings reveal that isatin is a useful framework for developing new anticancer drugs. In the future, nano‐formulation drug delivery systems with new drug signaling pathways will be promoted to increase bioavailability and targeted delivery, especially in solid tumors.

Metal-Based Combination Therapies in Cancer: Mechanistic Principles and Emerging Opportunities.

Metal-based anticancer agents occupy a distinctive niche in cancer therapy owing to their exceptional coordination versatility, redox activity, and tunable photochemical properties, which enable simultaneous engagement of multiple cellular pathways. Despite the clinical success of platinum-based chemotherapy, metal-based monotherapy is frequently hindered by resistance development, dose-limiting toxicity, and incomplete tumor control. Combination therapy has therefore emerged as an indispensable approach in clinical oncology, offering synergistic enhancement of antitumor efficacy, mitigation of resistance, and expansion of therapeutic windows. In this review, we summarize recent advances in metal-based anticancer combinations from three mechanistic perspectives. First, we categorize combinations of metal-based agents with mechanistically distinct chemotherapeutics based on their ability to reinforce DNA damage, promote apoptotic execution, disrupt redox homeostasis, and exploit metabolic vulnerabilities. Second, we discuss the immunomodulatory functions of metallodrugs, emphasizing their capacity to induce immunogenic cell death and reprogram tumor microenvironment, thereby establishing a rational basis for combinations with immune checkpoint blockade. Third, we explore emerging multimodal strategies in which metal-based systems function as energy-responsive agents, enabling photodynamic, photothermal, or sonodynamic therapy and rational integration with other modalities. Collectively, these insights provide a robust mechanistic foundation to guide the rational design of next-generation metal-based combination therapies for improved cancer treatment.

Biological Activities and Mechanism of Transition Metal Complexes as Novel Anticancer Agents for Different Cancer Cell Lines—A Review

Transition metal complexes have attracted considerable attention as promising anticancer agents because of their diverse coordination chemistry, tunable structures, and ability to modulate multiple cellular pathways. This review provides a critical overview of the recent advances in transition metal‐based therapeutics, highlighting the relationship between structural design and anticancer activity. The major mechanisms of action, including DNA interaction, reactive oxygen species generation, apoptosis induction, cell cycle arrest, inhibition of angiogenesis, and modulation of key signaling pathways, are discussed to illustrate how these complexes exert their therapeutic effects. Emphasis is placed on structure–activity relationships, examining how the metal center, ligand environment, coordination geometry, oxidation state, and physicochemical properties influence biological performance. Representative complexes of Pt, Zn, Cu, Ni, Au, Fe, Rh, and related transition metals are critically evaluated with respect to their anticancer efficacy and current limitations. Finally, emerging research directions, including rational molecular design, alternative biological targets, computational approaches, advanced characterization, and improved biological evaluation, are discussed to highlight future opportunities for developing safer, more selective, and clinically translatable transition metal‐based anticancer agents.