Cancer, characterized by uncontrolled cell proliferation, remains a global health challenge. Despite advancements in cancer treatment, drug resistance and adverse effects on normal cells remain challenging. The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase protein, is crucial in controlling cell proliferation and is implicated in various cancers. Here, the cytotoxic and apoptotic potential of 21 newly synthesized spiro-pyrrolopyridazine (SPP) derivatives was investigated on breast (MCF-7), lung (H69AR), and prostate (PC-3) cancer cells. XTT assay was used for cytotoxicity assessment. Flow cytometry and western blot (WB) analyses were conducted for apoptosis detection. Additionally, the EGFR inhibitory potential of these derivatives was evaluated via a homogeneous time-resolved fluorescence (HTRF) assay, and WB and molecular docking studies were conducted to analyze the binding affinities of SPP10 with EGFR. SPPs, especially SPP10, exhibit significant cytotoxicity across MCF-7, H69AR, and PC-3 cancer cells with IC₅₀ values of 2.31 ± 0.3, 3.16 ± 0.8, and 4.2 ± 0.2 μM, respectively. Notably, SPP10 demonstrates selective cytotoxicity against cancer cells with a low impact on nontumorigenic cells (IC₅₀ value: 26.8 ± 0.4 μM). Flow cytometric analysis demonstrated the potent induction of apoptotic cell death by SPP10 in all of the tested cancer cells. Western blot analysis revealed the involvement of key apoptotic proteins, with SPP10 notably inhibiting antiapoptotic Bcl-2 while inducing pro-apoptotic Bax and cytochrome c. SPP10 exhibited significant EGFR kinase inhibitory activity, surpassing the efficacy of the reference drug erlotinib. Molecular docking studies support these findings, revealing strong binding affinities of SPP10 with both wild-type and mutated EGFR. The study underscores the significance of heterocyclic compounds, particularly spiro-class heterocyclic molecules, in advancing cancer research. Overall, SPP10 emerges as a promising candidate for further investigations in cancer treatment, combining potent cytotoxicity, apoptotic induction, and targeted EGFR inhibition.

Although chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious side effects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.

Essential oil (EO) fractions of plants are complex mixtures of volatile compounds with broad-spectrum biological properties. In the current study, the EO content of Vitex agnus castus L. (VAC) leaves growing in the Aegean region of Turkey was extracted and identified. Then, VAC EOs were investigated for their potential antioxidant, cytotoxic and apoptotic effects in human H69AR multi-drug resistant cancer cells. EOs were isolated by hydrodistillation and chemical composition was determined by GC-MS. Cell viability was assessed via MTT and trypan blue assays. Antioxidant activity was evaluated by measuring the total antioxidant activity and free radical scavenging activity. Apoptosis was evaluated via DNA fragmentation and caspase 3/7 activity assays. Changes in the levels of apoptotic genes were determined by RT-qPCR. The results indicated strong antioxidant activity and cytotoxic effect on H69AR cancer cells but not on HEK-293 human normal cells indicating the tumor-specific effect. VAC EOs induced caspase 3/7 activation and apoptosis through triggering both extrinsic- and intrinsic-pathways by modulating Bcl-2, Bcl-XL, Bax, Bad, FADD, Caspase-8, Caspase-9, TRAIL R1/DR4 and TRAIL R2/DR5. This study revealed that VAC EOs may be a promising candidate in the development of novel therapeutic agents for multi-drug resistant lung cancer treatment.

Background/Objectives: Cancer is one of the world’s leading causes of death. In 2022 alone, 9.74 million people died of cancer. It is estimated that this figure will rise to 10.4 million by 2025. Prostate and breast cancer are the most frequently diagnosed cancers in the world. Methods: Notably, compound 9f displayed the highest activity against both prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. It was seen that substitution on the coumarin ring had a positive effect on anticancer activity (except chlorine substitution at the 6th position of coumarin), while it had a negative effect on the selectivity index (the ratio of IC₅₀ calculated for healthy and cancer cells). Conclusions: The findings are consistent with the results obtained in the Molecular Docking study. Molecular docking studies were performed to investigate the binding affinities of the synthesized compounds towards kinesin-associated motor protein EG5, Human Ribonucleotide Reductase and Human Topoisomerase II, confirming their potent in vitro cytotoxicity against cancer cell lines. In accordance with the findings of experimental studies, compound 9f demonstrated the optimal docking binding scores.

Breast cancer continues to pose a significant global health burden, highlighting the urgent need for novel chemotherapeutic agents with improved selectivity and reduced toxicity. In this study, we rationally designed and synthesized six novel amide‐bridged triazole‐coumarin hybrids ( 5a–f ) based on the known anticancer potential of both pharmacophores. The synthesized compounds were evaluated for their cytotoxicity in MCF‐7 and MDA─MB─231 breast cancer cell lines and non‐tumorigenic MCF‐10A cells. Among them, derivative 5f showed the most potent anticancer activity with minimal toxicity toward normal cells. Mechanistic studies revealed that 5f induced apoptosis by modulating Bax and Bcl─2 expression and arrested the cell cycle at the S phase via downregulation of CDK2 and Cyclin E. Molecular docking analyses confirmed its high binding affinity to CDK2 and Bcl─2, supporting its potential as a dual‐target inhibitor. These findings suggest that compound 5f is a promising lead structure for the development of selective anticancer agents targeting breast cancer.

A series of aryl–isatin Schiff base derivatives (3a–d) and their piano-stool ruthenium complexes (4a–d) were synthesized and characterized via ¹H and ¹³C NMR and Fourier transform infrared (FTIR) spectroscopy. In addition, the purity of all of the compounds (3a–c and 4a–d) was determined via elemental analysis. Complex 4d was analyzed using X-ray crystallography. An in vitro antiproliferative study of the compounds (3a–c and 4a–d) against human hepatocellular carcinoma (HEPG2), human breast cancer (MCF-7), human prostate cancer (PC-3), and human embryonic kidney (HEK-293) cells exhibited their considerable antiproliferative activity. 4d exhibited effective cytotoxicity against HEPG2 and MCF-7. It displayed higher cytotoxicity than the reference metallo-drug cisplatin. Moreover, the stability of 4d was studied via ¹H NMR spectroscopy, and the binding model between 4d and DNA was investigated via ultraviolet–visible spectroscopy. The lipophilicity of the synthesized complexes was determined using an extraction method.