Anti-Cancer Agents in Medicinal Chemistry - Online First
Description text for Online First listing goes here...
61 - 71 of 71 results
-
-
Precision-engineered Carrageenan Gels: Boosting the Efficacy, Selectivity, and Release of Celecoxib for Lung Cancer Therapy
Authors: Akanksha Bhatt, Priyank Purohit and Magda H. AbdellattifAvailable online: 12 May 2025More LessBackgroundLung cancer is one of the most widespread malignancies among all types of cancers. There is uncertainty in its treatment because of the selectivity. The investigation is aimed to enhance therapeutic efficacy through targeted improvements in drug selectivity and reduced toxicity by analyzing well-accepted cyclooxygenase (COX)-2, which is an enzyme target and a known therapeutic target for anti-inflammatory and antitumor agents.
ObjectiveThe objective of the present research was to identify the most suitable counterpart for celecoxib, which would produce synergistic effects and improve the selectivity index, safety, and efficacy of targeting cancer cells.
MethodsThe HOPE-62 cancer cell line and noncancerous LLC-MK2 cell line were used to analyze the activity of the prepared formulations. The effectiveness was compared by calculating the half-maximal inhibitory concentration (IC50) values of carrageenan, celecoxib, and celecoxib embedded with carrageenan. The release pattern of celecoxib from the carrageenan matrix was also determined by using a trans-diffusion cell; moreover, the binding sites of carrageenan and celecoxib were also evaluated through in silico molecular docking studies.
ResultsCarrageenan showed promising anticancer activity, with an IC50 value of 17.3±2 µM against the HOPE-62 cell line. When blended with celecoxib (15.6±2 µM), the combination achieved enhanced efficacy and improved selectivity over celecoxib alone (IC50 of 10.3±1.5 µM). In noncancerous LLC-MK2 cells, the IC50 values were observed to be significantly higher: 1484 ±6 µM in the combined formulation and with IC50 values of 559±3 µM and 878±4 µM, respectively, in celecoxib and carrageenan alone.
ConclusionThe carrageenan-embedded celecoxib exhibited a significant increase in the selectivity index from 32 to 144, which suggests enhanced anticancer activity with a favorable safety profile. Initially, sustained release of celecoxib from the blend was at a higher rate, but steadily maintained rates were. The In-silico docking studies also supported the synergistic activity of the combined form through separate interaction patterns without interfering with others. These findings underscore the therapeutic potential of excipient–drug blending strategies to achieve synergistic effects, excellent selectivity, and reduced toxicity in cancer treatments.
-
-
-
Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral
Authors: Run-Bin Tan and Yeannie Hui-Yeng YapAvailable online: 06 May 2025More LessTalimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC’s mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges—systemic delivery, immune clearance, and biomarker development for patient selection—are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC’s expanding role in cancer treatment, offering clinicians’ and researchers’ insights to optimize its therapeutic horizons across diverse malignancies.
-
-
-
Unraveling the Resistance: Challenges and Advances in PARP Inhibitor Therapy for BRCA1/2 Breast Cancer
Authors: Hongjun Tang, Jingsheng Chen, Kangwei Jiang, Jiangtao He, Fangming Tang, Dongbing Li and Yuye WuAvailable online: 06 May 2025More LessBreast cancer is the most prevalent malignant tumor among women globally, with breast cancer susceptibility genes (BRCA1 and BRCA2, BRCA1/2) mutations significantly increasing the risk of developing aggressive forms of the disease. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have shown promise in treating BRCA1/2-mutated breast cancer by exploiting deficiencies in homologous recombination (HR) repair. However, the emergence of acquired resistance poses a significant challenge. Our study examines the mechanisms of PARPi resistance in BRCA1/2-mutated breast cancer, synthesizing recent clinical advancements and identifying key resistance pathways, including HR recovery, DNA replication fork stability, and epigenetic modifications. We also highlight potential strategies to overcome these challenges to PARPi resistance, such as combination therapies and novel targets. Our comprehensive analysis aims to inform future clinical practices and guide the development of more effective treatment strategies.
-
-
-
Phytochemical Profiling and Anticancer Potential of Fagonia cretica L. Extracts on Liver Cancer (HepG2) Cells using In vitro and In silico Approaches
Available online: 03 May 2025More LessBackgroundCancer is a complex multifactorial disease charcterized by the progression of genetic and epigenetic changes in human cells. Plant-based derivatives with antioxidant and anticancer properties have been of great interest in treating several human ailments.
ObjectiveThis study investigates the in-vitro antioxidative, cytotoxic, and apoptotic activities of different Fagonia cretica L. (F. cretica) leaf extracts.
MethodsIn-vitro DPPH, nitric oxide, superoxide anion, and hydrogen peroxide assays were used to evaluate the antioxidative potential of ethanolic extract of F. cretica (EFC) and hexane extract of F. cretica (HFC). The antiproliferative potential was determined using MTT, crystal violet, and annexin V/PI staining protocols on liver cancer (HepG2) and noncancerous (HEK-293) cell lines. Through in silico analysis, bioactive drug-like phytocompounds identified by GC-MS were evaluated.
ResultsHigher concentrations of total flavonoid contents (TFCs), total phenolic contents (TPCs), and tannins with strong antioxidant potential were observed in EFC extract as compared to HFC extract. Furthermore, the EFC extract proved to be more cytotoxic with a selective index (SI) of 12.92 than HFC (SI; 5.46) towards experimental cell lines. Moreover, EFC extract showed 82.31% apoptotic induction on HepG2 cells compared to hexane extract and cisplatin (standard drug). From the GC-MS analysis of F. cretica, 32 bioactive compounds were identified from the EFC extract and 21 from the HFC extract. In silico study revealed that 5-(4,5-Dihydro-3H-pyrrol-2-ylmethylene)-4,4-dimethylpyrrolidine-2-thione showed the highest docking score of -8.9 kcal/mol and -8.6 kcal/mol against TNF-α and TGF-β, respectively.
ConclusionIn conclusion, EFC extract and its bioactive compounds have a scientifically proven role in liver cancer management, but further research is required to validate their therapeutics through clinical trials.
-
-
-
Synthesis and Biological Studies of Aurones Derivatives for its Anticancer Potential
Authors: Kulkarni P Yogesh and Pramod L. IngaleAvailable online: 25 April 2025More LessBackgroundAurone based compounds exhibited antioxidant and anti-inflammatory potential and documented for their anticancer potential. The anticancer potential of aurone derivatives AU3, AU4, AU5, AU7, and AU10 is yet to be studied against breast cancer.
ObjectiveThe present work was undertaken to evaluate the anticancer potential of aurone based test compounds AU3, AU4, AU5, AU7, and AU10 in breast cancer cell lines MCF-7.
MethodsThe azaindole based aurones were synthesized by the condensing 4,6-dimethoxybenzofuran-3(2H)-one derivative with various indole aldehydes in the presence of sodium hydroxide. The MCF-7 breast cancer cell line was used to assess the cytotoxic effects of these compounds. Molecular docking studies of the synthesized compounds against the Cyclin-dependent kinase 2 (CDK2)/Cyclin A complex were conducted.
ResultsOur experimental findings demonstrated that AU3, AU4, AU5, AU7, and AU10 elicited significant effects on MCF-7 by virtue of its minimum cell viability, with IC50 values of 70.14 µM, 87.85 µM, 133.21 µM, 52.79 µM, and 99.55 µM, respectively, thus, exhibits potential anticancer action. Further, to corroborate the anticancer potential, we investigated mechanisms of action through molecular docking studies with the CDK2/Cyclin A complex (PDB: 6GUC) and their findings demonstrated that test compounds showed robust binding through various interactions, including hydrogen bonds, Pi-interactions, and Alkyl bonds with key residues such as Lys129, Asp127, Gln131, and Asp145. Test compounds AU3 and AU7, exhibited better binding affinities and diverse interaction profiles, suggesting a potent disruption of CDK2/Cyclin A activity.
ConclusionThus, in conclusion, our findings revealed that AU3, AU4, AU5, AU7, and AU10 elicited anticancer action and their effects through CDK2/Cyclin A disruption.
-
-
-
Clinical Characteristics and Prognostic Factors Associated with Herpes Zoster in Patients with Malignant Tumors: A Systematic Review and Meta-analysis
Authors: Mingming Ding, Shantao Qiu and Guan JiangAvailable online: 07 April 2025More LessBackgroundHerpes zoster (HZ) is a common complication in patients with malignant tumors (MT), impacting prognosis. Immunocompromised states due to malignancy or treatment increase HZ risk. However, comprehensive assessments of HZ's clinical features and its impact on prognosis in these patients are limited, general conclusions are challenging, prompting a systematic review and meta-analysis to better understand the relative risk of HZ in malignancy.
ObjectiveTo assess the clinical features and prognostic factors of HZ in cancer patients through systematic review and meta-analysis. The study aimed to calculate the relative risk of HZ in malignancy and analyze factors affecting prognosis, such as age, gender, tumor type, and treatment.
MethodsA systematic search in PubMed (2016-2024) identified studies on HZ and malignancy. Two reviewers independently screened and selected studies, extracting data on study characteristics, population demographics, and outcomes. Statistical heterogeneity across the studies was addressed using random-effects models, while subgroup analyses were performed to identify potential sources of heterogeneity.
ResultsOut of the 633 records reviewed, 13 studies satisfied the eligibility criteria and were incorporated into the meta-analysis. The combined relative risk for any type of cancer was found to be 1.82(95% CI: 1.29,2.57). The combined relative risk for any solid tumors was 1.63(95% CI: 1.08,2.46). The combined relative risk for any haematological cancer was 3.43(95% CI: 1.33,8.86). The combined analysis of all treatment modalities (including Radiotherapy, Chemotherapy, Immunosuppression, HSCT) shows a significant overall effect with a risk ratio of 1.78(95%CI: 1.59,2.00).
ConclusionCancer patients have increased HZ risk due to immunosuppression from the malignancy and its treatment, especially in hematological cancers and those undergoing stem cell transplantation.
-
-
-
A Review of Cryptotanshinone and its Nanoformulation in Cancer Therapy
Authors: Xin Liu, Yahan Gao, Fan Yang, Min Qian, Shuhui You, Xiaoxiao Wang, Fenju Qin, Min Xiang and Weiqiang GuoAvailable online: 28 March 2025More LessCancer, with a high incidence and mortality rate, has emerged as a major public health problem worldwide. Currently, new approaches, such as targeted therapy and immunotherapy, are giving hope to patients. However, drug resistance and adverse side effects are major barriers to cancer treatment. As a result, there is a greater focus on the development of cancer therapy strategies and medications with low toxicity and high efficacy. Cryptotanshinone (CTS), a diterpenoid quinone extracted from Salvia miltiorrhiza Bunge, exhibits a wide range of biological activities, including immunomodulatory, anti-inflammatory, and antitumor effects. In recent years, numerous studies have highlighted its significant antitumor properties, indicating potential clinical applications and development value. However, the clinical use of cryptotanshinone has been limited due to its poor water solubility and low bioavailability. To overcome these limitations, researchers are exploring new drug delivery systems, and novel formulation systems based on nanotechnology are being developed to improve the delivery and effectiveness of cryptotanshinone. In this review, we aim to consolidate the existing knowledge regarding the antitumor effects of cryptotanshinone and emphasize the latest advancements in its nanoformulation development. We hope to provide insights that will further improve the antitumor efficacy and clinical applicability of cryptotanshinone.
-
-
-
Recent Advances in Therapeutic Potential of Dual-Acting Aromatase/COX-2
Available online: 26 March 2025More LessAromatase, a crucial enzyme assigned for transforming androgen into estrogen, has a vital function in the advancement of drug-resistant breast cancers that respond to endocrine treatments. Aromatase (CYP19A1) is a monooxygenase from the cytochrome P450 family that is involved in the conversion of androgens to estrogens. Breast cancer cells express aromatase activity, indicating that the tumor cells may be able to produce local estrogen. By inhibiting aromatase, serum estrogen levels decrease, which, in turn, hinders estrogen-driven cancer cell growth in hormone receptor-positive breast cancer cases. In this sense, the introduction of novel aromatase inhibitors could be a significant step forward in the fight against cancer. This is especially true in hormone-dependent cancers. Many compounds have been introduced as aromatase inhibitors, classified as steroidal or nonsteroidal. However, it should be noted that these drugs have encountered resistance in numerous cases, particularly in recent years. Thus, the search for new aromatase inhibitor drugs has always been critical. Newly, there seems to be a surge of enthusiasm in the discovery and production of molecules with dual inhibitory effects, which can inhibit two or more enzymes simultaneously. This method enables a significant reduction in potential drug resistance. The design of these compounds has an opportunity to significantly boost the efficacy of anti-cancer treatments by causing synergistic effects. This article offers a review of newly developed aromatase inhibitors with potential anticancer effects.
-
-
-
Unraveling the Role of Tumor-infiltrating Immune Cells in Modulating Cancer Drug Resistance
Available online: 24 March 2025More LessTumor-infiltrating immune cells (TIICs) have been identified as critical components in the development of cancer drug resistance. This review aims to discuss the various types of TIICs, such as macrophages and T cells, that have been linked to cancer drug resistance. Furthermore, we explore the mechanisms by which TIICs contribute to drug resistance and how these mechanisms may differ across various tumor types. Additionally, we examine the potential of immune checkpoint inhibitors in combination with traditional cancer therapies as a strategy to overcome TIIC-mediated cancer drug resistance. In conclusion, this review provides an in-depth analysis of the current knowledge on the role of TIICs in cancer drug resistance and highlights potential avenues for future research to develop more effective treatment strategies. The findings presented in this review emphasize the importance of understanding the complex interactions between cancer cells and the immune system in order to develop novel therapeutic approaches that can overcome TIIC-mediated cancer drug resistance.
-
-
-
Synthesis and Evaluation of Optical Properties, SHP2 Inhibitory Activity, and Cellular Imaging for Novel 2-Quinolone Derivatives
Authors: Chun Zhang, Yuting Yang, Li-Xin Gao, Suya Gan, Jia Li, Xin Wang, Yu-Bo Zhou and Wen-Long WangAvailable online: 17 March 2025More LessIntroductionAlthough the development of SHP2 inhibitors has made striking progress, there is no inhibitor in clinical evaluation because of the potential side effects induced by poor drug distribution. Fluorescence imaging technology is widely used in the process of diagnosis and treatment of diseases because of the advantages of rapid imaging and non-destructive detection and might provide a new way to explore the mechanism of drug-target interactions in intact tissue.
MethodsA series of 2-quinolone derivatives as fluorescent inhibitors against SHP2 were designed and synthesized, and their spectral properties and biological activities were evaluated in this report. The representative compound 8A had excellent fluorescence properties (: 562 nm, Stokes shift: 170 nm, fluorescence quantum yield: 0.072) and optical stability.
ResultsMoreover, compound 8A emitted a blue signal in SHP2WT U2OS cells and inhibited the SHP2 enzyme abilities (IC50: 20.16 ± 0.95 μM) without the extra combination of suitable fluorophores, linker, or selective-activated molecules.
ConclusionTherefore, we hope that compound 8A could act as a lead to develop novel, convenient, and bifunctional chemical tools to explore the mechanism of drug-target interactions in intact tissue and promote the integrated research progress of diagnosis and treatment of SHP2 related diseases.
-
-
-
The Function of Poly (U) Binding Splicing Factor 60 (PUF60) in Disease Regulation
Authors: Huijuan Chen, Tian Guan, Jingfeng Song and Yihua ChenAvailable online: 03 January 2025More LessThe alternative splicing (AS) of pre-mRNA is an important process in controlling the expression of human genes, which can enrich the diversity of the proteome and regulate gene function. On the contrary, aberrant splicing contributes significantly to numerous human diseases progression, including tumors, neurological diseases, metabolic diseases, infections, and immune diseases. The PUF60, a protein related to RNA splicing, plays critical functions in RNA splicing and gene transcription regulation. In addition, it can achieve synergistic binding with U2AF65 on RNA through interactions in the pyrimidine region, promoting the splicing of introns with weak 3'- splice sites and pyrimidine bundles. Nevertheless, an increasing amount of evidence supports that it shows a significant overexpression pattern in the vast majority of cancer cells and is crucial for embryonic development, indicating that PUF60 may hold the post of a potential therapeutic target for such diseases. These studies have significantly increased our interest in PUF60. Thus, we briefly reviewed the structural domain characteristics of the PUF60, splicing mutants of PUF60, and the roles and functions in human diseases, including various cancers, infections of bacterium and viruses, myositis, and Verheij syndrome. Furthermore, the targeted PUF60 inhibitors and boundedness of the current research were elaborated on in the article. The article effectively communicates critical perception and insight, making it a precious resource for those interested in PUF60 research and treatment.
-