Candidate Anticancer Agent Research Articles

Anticancer Potential of Quercetin on Oral Squamous Cell Carcinoma: A Scoping Review and Molecular Docking.

Oral squamous cell carcinoma (OSCC) is a type of cancer that has a low survival rate and high recurrence and metastasis rates. To date, there is still no effective treatment for OSCC. Various types of cancer, including OSCC, have reported quercetin to act as an anticancer agent, but there is no clear research data on how it may affect OSCC. To determine the anticancer potential of quercetin in OSCC, we conducted a scoping review, and to determine the interaction of quercetin with one of the proteins that plays a role in carcinogenesis, namely, BCL-2, we conducted molecular docking. The scoping review process was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. The scoping review was searched by collecting articles related to the research topic in Google Scholar, PubMed, ScienceDirect, Cochrane, and EBSCOhost databases. All of the literature records found during the search were imported into the Mendeley software to remove duplication. Nine studies were generated after the titles and abstracts were reviewed according to the inclusion and exclusion criteria. After the full-text screening, no studies were excluded, leaving nine publications determined to be eligible for inclusion in the scoping review. Quercetin showed effects on inhibiting cancer invasion, migration, proliferation, and many protein expressions, as well as increasing cell apoptosis. Molecular docking was done for quercetin and BCl-2 protein. Doxorubicin was utilized as a comparison ligand. The in silico study was utilized using AutoDock Vina, AutoDock Tools 1.5.6, Biovia Discovery Studio 2021, and PyMol. Molecular docking indicated quercetin has a strong binding affinity with BCl-2 protein (ΔG -7.2 kcal/mol). Both scoping review and molecular docking revealed that quercetin is a promising candidate for anticancer agent.

Antioxidative and Apoptotic Activities of Vernonia amygdalina Ethanolic Extract in the AOM/DSS Mice Model of Colon Cancer

This study examined the efficacy and safety of Vernonia amygdalina ethanol extract (VAEE) therapy in treating azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon cancer in mice, aiming to uncover the underlying mechanisms. A colon cancer mice model was used to evaluate the effects of VAEE on antioxidant enzyme levels and apoptosis. VAEE treatment increased SOD and caspase-3 levels while reducing MDA and Bcl-2 levels. These results indicate the potential of VAEE as an anticancer agent, with several doses showing significant increases in SOD and caspase-3 levels while significantly reducing MDA and Bcl-2 levels compared to the negative control (p<0.05). A dose of 500 mg/kg BW appears to be a potential candidate anticancer agent. Further studies on the molecular mechanisms and long-term effects are needed to support clinical applications. Keywords: Antioxidants, AOM/DSS, Apoptosis, VAEE, Colon Cancer

First voltammetric analysis of two possible anticancer drug candidates using an unmodified glassy carbon electrode

Dimethyl 2-[2-(1-phenyl-4,5-dihydro-1H-imidazol-2-yl)hydrazinylidene]butanedioate (DIHB) and 8-(3-chlorophenyl)-2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-dione (HDIT) are promising candidates for anticancer agents, the first analytical procedures of which are presented in this paper. The commercially available unmodified glassy carbon electrode (GCE) was used as a sensor for the individual and simultaneous differential pulse voltammetric (DPV) determination of these possible anticancer drugs. The findings concerning the electrochemical behaviour indicated that DIHB and HDIT display at GCE, as a sensor, the oxidation peaks at 1.18 and 0.98 V, respectively (vs. Ag/AgCl, 3.0 mol L−1 KCl) in the 0.125 mol L−1 acetate buffer of pH = 4.5, which were employed for their quantification. Various experimental parameters were carefully investigated, to achieve high sensitivity in voltammetric measurements. Finally, under the optimised conditions (t of 60 s, ΔEA of 75 mV, ν of 225 mV s−1, and tm of 2 ms), the proposed DPV procedure with the GCE demonstrated broad linear sensing ranges (1–200 nmol L−1—DIHB and 5–200 nmol L−1—HDIT), boasting the detection limits of 0.18 nmol L−1 for DIHB and 1.1 nmol L−1 for HDIT. Moreover, the developed procedure was distinguished by good selectivity, repeatability of DIHB and HDIT signals and sensor reproducibility. The practical application of this method was demonstrated by analysing the urine reference material without any prior treatment. The results showed that this environmentally friendly approach, with a modification-free sensor, is suitable for the sensitive, selective and rapid quantification of DIHB and HDIT.

Aspongopus chinensis ach-miR-276a-3p induces breast cancer cell cycle arrest by targeting APPL2 to regulate the CDK2-Rb-E2F1 signaling pathway

Breast cancer, the most common cancer, presents a significant challenge to the health and longevity of women. Aspongopus chinensis Dallas is an insect with known anti-breast cancer properties. However, the anti-breast cancer effects and underlying mechanisms have not been elucidated. Exogenous microRNAs (miRNAs), which are derived from plants and animals, have been revealed to have notable capacities for controlling the proliferation of cancerous cells. To elucidate the inhibitory effects of miRNAs derived from A. chinensis and the regulatory mechanism involved in the growth of breast cancer cells, miRNA sequencing was initially employed to screen for miRNAs both in A. chinensis hemolymph and decoction and in mouse serum and tumor tissue after decoction gavage. Subsequently, the experiments were performed to assess the suppressive effect of ach-miR-276a-3p, the miRNA screened out from a previous study, on the proliferation of MDA-MB-231 and MDA-MB-468 breast cancer cell lines in vitro and in vivo. Finally, the regulatory mechanism of ach-miR-276a-3p in MDA-MB-231 and MDA-MB-468 breast cancer cells was elucidated. The results demonstrated that ach-miR-276a-3p notably inhibited breast cancer cell proliferation, migration, colony formation, and invasion and induced cell cycle arrest at the G0/G1 phase. Moreover, the ach-miR-276a-3p mimics significantly reduced the tumor volume and weight in xenograft tumor mice. Furthermore, ach-miR-276a-3p could induce cell cycle arrest by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway. In summary, ach-miR-276a-3p, derived from A. chinensis, has anti-breast cancer activity by targeting APPL2 and regulating the CDK2-Rb-E2F1 signaling pathway and can serve as a promising candidate anticancer agent.

Boric Acid Affects Cell Proliferation, Apoptosis, and Oxidative Stress in ALL Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a type of acute lymphoblastic leukemia from early T-cell progenitors. Interest grows in creating less toxic agents and therapies for chemo-resistant T-ALL cancer. Recently, elemental boron has special properties useful in the creation of new drugs. Studies have revealed the cytotoxic properties of boric acid (BA) on cancer, but not fully understood. We aimed to investigate the effect of BA on cell proliferation, apoptosis, and oxidative stress in the Jurkat cells. The effects of BA on cell viability were determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay for 24-48-72 h. The impact of BA on apoptosis was analyzed by acridine orange/ethidium bromide. Expression of apoptosis regulatory genes (Bcl-2, Bax, Caspase-3-8-9) and apoptotic miRNA (miR-21) was used by real-time quantitative polymerase chain reaction (RT-qPCR). The total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) value were calculated for oxidative stress. We determined the cytotoxic activity of BA on Jurkat cells by using XTT and defined the IC50 concentration (802.7 μg/mL) of BA. The findings clearly show that BA inhibited Jurkat cell proliferation dose-dependently. BA induced apoptosis through downregulated anti-apoptotic genes, and upregulated pro-apoptotic genes. Additionally, we found that BA significantly reduced the expression of miR-21 (p<0.001). Our findings demonstrated that different doses of BA increased TAS levels while decreasing TOS levels in Jurkat cells. Our study suggests that BA might be potential anti-cancer agent candidate in ALL via inhibition of cell proliferation, induced apoptosis, and reducing the amounts of anti-oxidants in cells.

A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity.

Antimicrobial peptides have gradually attracted interest as promising alternatives to conventional agents to control the worldwide health threats posed by antibiotic resistance and cancer. Crabrolin is a tridecapeptide extracted from the venom of the European hornet (Vespa crabro). Its antibacterial and anticancer potentials have been underrated compared to other peptides discovered from natural resources. Herein, a series of analogs were designed based on the template sequence of crabrolin to study its structure-activity relationship and enhance the drug's potential by changing the number, type, and distribution of charged residues. The cationicity-enhanced derivatives were shown to have improved antibacterial and anticancer activities with a lower toxicity. Notably, the double-arginine-modified product, crabrolin-TR, possessed a potent capacity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 4 μM), which was around thirty times stronger than the parent peptide (MIC = 128 μM). Furthermore, crabrolin-TR showed an in vivo treatment efficacy in a Klebsiella-pneumoniae-infected waxworm model and was non-toxic under its maximum MBC value (MIC = 8 μM), indicating its therapeutic potency and better selectivity. Overall, we rationally designed functional peptides by progressively increasing the number and distribution of charged residues, demonstrating new insights for developing therapeutic molecules from natural resources with enhanced properties, and proposed crabrolin-TR as an appealing antibacterial and anticancer agent candidate for development.

Snoopligase-catalyzed molecular glue enables efficient generation of hyperoligomerized TRAIL variant with enhanced antitumor effect

Clinical application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is predominantly limited by its inefficient apoptosis induction in tumor cells, which might be improved by using molecular superglue-mediated hyperoligomerization to increase its valency. Here, the minimal superglue peptide pairs, including Snoopligase-catalyzed SnoopTagJr/SnoopDogTag and SpyStapler-catalyzed SpyTag/SpyBDTag, were individually fused at the N- or C-terminus of the TRAIL promoter to produce superglue-fusion TRAIL variants. Similar to native trivalent TRAIL, these superglue-fusion TRAIL variants were highly expressed in Escherichia coli (E. coli) and spontaneously trimerized. In the presence of Snoopligase or SpyStapler, the trivalent superglue-fusion TRAIL variants were predominantly crosslinked into hexavalent TRAIL variants. Nevertheless, Snoopligase was more efficient than SpyStapler in the production of hexavalent TRAIL variants. In particular, Snoopligase-catalyzed trivalent TRAIL variants with N-terminal fusion of SnoopTagJr/SnoopDogTag produced hexavalent SnHexaTR with the highest yield (∼70%). The in vitro cytotoxicity of SnHexaTR was 10–40 times greater than that of TRAIL in several tumor cells. In addition, compared to trivalent TRAIL, hexavalent SnHexaTR showed a longer serum half-life and greater tumor uptake, which resulted in eradication of 50% of tumor xenografts of TRAIL-sensitive COLO 205. In mice bearing TRAIL-resistant HT-29 tumor xenografts, hexavalent SnHexaTR combined with bortezomib encapsulated in liposomes also showed robust tumor growth suppression, indicating that hyperoligomerization mediated by minimal molecular superglue significantly increased the cytotoxicity and antitumor effect of TRAIL. As a novel anticancer agent candidate, the hexavalent SnHexaTR has great potential for clinical application in cancer therapy.

Does Boric Acid Inhibit Cell Proliferation on MCF-7 and MDA-MB-231 Cells in Monolayer and Spheroid Cultures by Using Apoptosis Pathways?

Most breast cancers originate in the lobules or ducts of the breast. Breast cancer as the second main cause of death among women in the world is the most common kind of cancer in women. Studies have been conducted to find the optimal treatment for breast cancer. Moreover, the therapeutic effects of different drugs and substances on this disease have been intensively researched. Boric acid accounts for 96% of the boron content in body fluids, and its derivatives are absorbed by the human body. It is assumed to be represented as (B(OH)2). Experimental studies have shown a reduction of cell proliferation and stimulation of apoptosis in some melanoma, prostate, and colon cancer cell lines through boric acid. The aim of this study was to investigate if boric acid could be used for treating breast cancer. The impacts of boric acid on the human breast carcinoma cell lines MCF-7 and MDA-MB-231 were studied with TUNEL, BrdU, caspase-3, and endo-G immunohistochemical studies in 3D and 2D culture systems. Furthermore, we conducted a qRT-PCR study to show changes in the expression of some genes involved in apoptosis. Suppression of cell proliferation through boric acid-inducing apoptosis was observed both in 3D and 2D culture conditions. These results are compatible with the gene expression results. The ENDOG, CASP3, CASP8, and CASP9 gene expression significantly changed at all time intervals in MCF-7 and MD-MB-231 cell lines boric acid can potentially treat breast cancer as an anti-cancer agent candidate.

Bee Venom Induces the Interaction between Phosphorylated Histone Variant, H2AX, and the Intracellular Site of beta-Actin in Liver and Breast Cancer Cells.

Bee venom is a natural mixture and candidate anti-cancer agent with selective cytotoxic effect on some cancer cells. However, the cellular mechanisms of how bee venom selectively targets cancer cells remain elusive. The aim of this study was to reveal the genotoxic effect of bee venom in concordance with the location of β-actin protein throughout the nucleus or/and cytoplasm. For this aim, the level of H2AX phosphorylation (γH2AX) and intracellular location of β-actin were assessed by immunofluorescence in liver (HEPG2) and metastatic breast (MDA-MB-231) cancer cell lines compared to normal fibroblasts (NIH3T3) after bee venom treatment. Colocalisation profiles of γH2AX and β-actin in each cell line were also analysed. The results showed that the levels of γH2AX staining decreased in normal cells but increased in cancer cells. The majority of β-actin was localised within the cytoplasm of normal cells after bee venom treatment, but it was mostly accumulated within the nucleus in cancer cells. Colocalisation of β-actin and γH2AX both in nucleus and cytoplasm was induced in each cancer cell by different patterns. The results showed that normal and cancerous cells had different responses against bee venom, and suggested that bee venom induced a cellular response by the interaction between γH2AX and β-actin.

Thiopurines Analogues with Additional Ring: Synthesis, Spectroscopic Properties, and Anticancer Potency.

Purine scaffolds constitute a starting point for the synthesis of numerous chemotherapeutics used in treating cancer, viruses, parasites, as well as bacterial and fungal infections. In this work, we synthesized a group of guanosine analogues containing an additional five-membered ring and a sulfur atom at the C-9 position. The spectral, photophysical, and biological properties of the synthesized compounds were investigated. The spectroscopic studies revealed that a combination of the thiocarbonyl chromophore and the tricyclic structure of guanine analogues shifts the absorption region above 350 nm, allowing for selective excitation when present in biological systems. Unfortunately, due to the low fluorescence quantum yield, this process cannot be used to monitor the presence of these compounds in cells. The synthesized compounds were evaluated for their effect on the viability of human cervical carcinoma (HeLa) and mouse fibroblast (NIH/3T3) cells. It was found that all of them display anticancer activity. In vitro studies were preceded by in silico ADME and PASS analyses, which confirmed that the designed compounds are promising candidates for anticancer agents.

Green synthesis of silver nanoparticles using Callisia fragrans leaf extract and its anticancer activity against MCF-7, HepG2, KB, LU-1, and MKN-7 cell lines

Abstract This article presents a simple, eco-friendly, and green method for the synthesis of silver nanoparticles (AgNPs) from AgNO3 solution utilizing an aqueous extract of Callisia fragrans leaf. The effects of C. fragrans leaf extraction conditions were evaluated. Parameters affecting the synthesis of AgNPs, such as the volume of extract, pH, temperature, and reaction time were investigated and optimized. The obtained AgNPs were analyzed by UV–Vis spectroscopy, X-ray diffraction pattern, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and FTIR techniques. TEM and DLS analyses have shown that the synthesized AgNPs were predominantly spherical in shape with an average size of 48 nm. The zeta potential of the colloidal solution of AgNPs is −27 mV, indicating the dispersion ability of AgNPs. The results of GC–MS and FTIR analyses show the presence of biomolecules in the aqueous extract of C. fragrans leaf that acts as reducing and capping agents for the biosynthesis of AgNPs. The synthesized AgNPs demonstrate anticancer activity against MCF-7, HepG2, KB, LU-1, and MKN-7 cell lines, with inhibitory concentrations at 50% (IC50 values) of 2.41, 2.31, 2.65, 3.26, and 2.40 µg·mL−1, respectively. The obtained results in the study show that the biosynthesized AgNP from C. fragrans leaf extract can be further exploited as a potential candidate for anticancer agents.

Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents

Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1–21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 μM), HCT116 (16.26 ± 1.94 μM) and HeLa (17.07 ± 1.09 μM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy.

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect.

Cardiac glycosides (CGs) are candidate anticancer agents that function by increasing [Ca2+]i to induce apoptotic cell death in several types of cancer cells. However, new findings have shown that the anti‑cancer effects of CGs involve complex cell‑signal transduction mechanisms. Hence, exploring the potential mechanisms of action of CGs may provide insight into their anti‑cancer effects and thus aid in the selection of the appropriate CG. Periplocymarin (PPM), which is a cardiac glycoside, is an active ingredient extracted from Cortex periplocae. The role of PPM was evaluated in HepG2 cells and xenografted nude mice. Cell proliferation, real‑time ATP rate assays, western blotting, cell apoptosis assays, short interfering RNA transfection, the patch clamp technique, electron microscopy, JC‑1 staining, immunofluorescence staining and autophagic flux assays were performed to evaluate the function and regulatory mechanisms of PPM invitro. The invivo activity of the PPM was assessed using a mouse xenograft model. The present study demonstrated that PPM synchronously activated lethal apoptosis and protective autophagy in liver cancer, and the initiation of autophagy counteracted the inherent pro‑apoptotic capacity and impaired the anti‑cancer effects. Specifically, PPM exerted a pro‑-apoptotic effect in HepG2 cells and activated macroautophagy by initiation of the AMPK/ULK1 and mTOR signaling pathways. Activation of macroautophagy counteracted the pro‑apoptotic effects of PPM, but when it was combined with an autophagy inhibitor, the anti‑cancer effects of PPM in mice bearing HepG2 xenografts were observed. Collectively, these results indicated that a self‑limiting effect impaired the pro‑apoptotic effects of PPM in liver cancer, but when combined with an autophagy inhibitor, it may serve as a novel therapeutic option for the management of liver cancer.

Structure Elucidation of 16 Undescribed Steroidal Glycosides from the Underground Parts of Agapanthus africanus and Apoptosis-Inducing Activity in Small-Cell Lung Cancer Cell.

To explore new candidates for anticancer agents from natural products, the underground parts of Agapanthus africanus, commonly used as an ornamental plant, were investigated phytochemically. As a result, 16 undescribed steroidal glycosides (1-16) were obtained, and their structures were determined mainly by NMR spectroscopic analysis and chemical transformations. The cytotoxic activities of the isolated compounds (1-16) against SBC-3 human small-cell lung cancer cells, A549 human adenocarcinoma cells, and HL-60 human promyelocytic leukemia cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay. Compound 1, a bisdesmosidic furostanol glycoside, and 10, a bisdesmosidic spirostanol glycoside, were cytotoxic to all three cell lines with IC50 values ranging from 1.2 to 13 μM. As 1 exhibited the most potent cytotoxicity against SBC-3 cells among the isolated compounds, its apoptosis-inducing activity toward SBC-3 cells was examined. Compound 1 arrested SBC-3 cells at the G2/M phase of the cell cycle and effectively induced apoptosis via an intrinsic pathway accompanied by the dissipation of membrane potential and morphological changes in mitochondria.

Antiangiogenic Activity of n-hexane Insoluble Fraction and Its Tylophorine Component from Ficus septica Leaves in Chicken Chorioallantoic Membrane Induced by bFGF.

Ficus septica is an Indonesian medicinal plant traditionally used to treat various illness, including cancer. The n-hexane insoluble fraction of the ethanolic extract of F. septica leaves (HIFFS) shows a potential anticancer activity against breast cancer cell line T47D. Considering that angiogenesis is a pivotal factor in malignant cancer growth, progression, and invasion, we aimed to investigate the antiangiogenic effect of HIFFS on chicken chorioallantoic membrane (CAM) induced by bFGF. We also evaluated tylophorine, the cytotoxic alkaloid of F. septica. Chicken CAM was used to assess the antiangiogenic effect. Fertilized chicken eggs were induced with basic fibroblast growth factor (bFGF) ex ovo. Prior to bFGF induction, HIFFS (2.33, 4.65, 6.98, and 9.30 μg/mL) or tylophorine (9.20 µM) was added (10 µL) to a paper disk and implanted to the CAM. After 48 h of incubation, each treatment group was photographed, and the number of new blood vessel was calculated and compared with that in the solvent-treated group to determine the antiangiogenic activity. Histology of the CAM was evaluated after hematoxylin-eosin and Mallory acid fuchsin staining. We found that HIFFS at low concentrations (2.33, 4.65, 6.98, and 9.30 μg/mL) inhibited angiogenesis activity (31.87, 41.99, 53.65, and 70.08, respectively) in chicken CAM induced by bFGF. Tylophorine (9.20 µM) also showed similar antiangiogenesis activity in the same model. Histopathology analysis revealed that HIFFS and tylophorine reduced the number of new blood vessels in CAM induced by bFGF. HIFFS and tylophorine showed antiangiogenic effect on chicken CAM induced by bFGF. This finding emphasized the potential of F. septica as a candidate anticancer agent.

Exploring Scutellaria baicalensis bioactives as EGFR tyrosine kinase inhibitors: Cheminformatics and molecular docking studies

The Epidermal Growth Factor Receptor (EGFR) pathway plays a pivotal role in cancer progression, making it a prime target for anticancer drug development. Scutellaria baicalensis, a traditional Chinese medicinal herb, harbors bioactive compounds with promising pharmacological properties, including potential EGFR tyrosine kinase inhibition. In this study, we employed a comprehensive approach merging cheminformatics and molecular docking techniques to investigate the glioblastoma multiforme inhibitory potentials of the bioactive compounds from the plant, with a focus against EGFR. Our findings revealed significant binding affinities ranging from −9.010 to −6.427 kcal/mol and intricate molecular interactions between compounds from S. baicalensis and the EGFR. Notably, Ganhuangenin, 5,7,2′,5′-tetrahydroxyflavone, (2R)-2-(2,6-dihydroxyphenyl)-3,4-dihydro-2H-chromene-5,7-diol, and tenaxin I showed particularly high binding affinities, with scores ranging from −9.010 to −8.649 kcal/mol. These compounds even outperformed erlotinib, a standard ligand with a score of −8.539 kcal/mol. Importantly, they interacted with key amino acid residues (Met769, Glu738, and Thr766) through hydrogen bonding. These interactions were driven by specific structural features, including aromatic rings, hydrogen bond donors and acceptors, and hydrophobic interactions and the reliability of these results was further confirmed through induced-fit docking, reinforcing the potential inhibitory effects of these compounds on the flexible protein. Additionally, all of the top-scoring compounds from S. baicalensis adhered to established drug-likeness rules, including Lipinski's criteria, Ghose's rules, Veber's guidelines, and Egan's rules. However, it's worth noting that scutellarin had some violations in these rules. Remarkably, none of the identified compounds were likely to cause hepatotoxicity, mutagenicity, or cytotoxicity, suggesting that they could be considered as safe candidates for anti-cancer agents. This multidisciplinary investigation bridges traditional herbal knowledge and modern drug discovery, offering insights into the potential of S. baicalensis bioactive compounds as novel EGFR-targeting agents. The results underscore the value of chemoinformatics and molecular docking studies in exploring natural compounds for cancer therapy, paving the way for further research in the field.

Sensitive and Selective Voltammetric Sensor Based on Anionic Surfactant-Modified Screen-Printed Carbon for the Quantitative Analysis of an Anticancer Active Fused Azaisocytosine-Containing Congener

3-(4-Nitrophenyl)-8-(2,3-dimethylphenyl)-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one (NDIT) is one of the most promising candidates for anticancer agents. Hence, a sensitive and selective sodium dodecyl sulfate-modified screen-printed carbon sensor (SPCE/SDS) was used for its quantitative analysis. The SPCE/SDS, in contrast to the SPCE, showed excellent behavior in the electrochemical reduction of NDIT by differential-pulse adsorptive stripping voltammetry (DPAdSV). Cyclic voltammetric (CV) studies reveal an irreversible, two-stage and not purely diffusion-controlled reduction process in 0.01 M HNO3. The sensor was characterized by CV and electrochemical impedance spectroscopy (EIS). Under the optimized conditions (t 45 s, ΔE 175 mV, ν 150 mV/s, and tm 5 ms), the DPAdSV procedure with the SPCE/SDS presented a very wide linear range from 1 to 2000 nM and a low detection limit of 0.29 nM. A 1000-fold excess concentration of potential interferents commonly present in biological samples did not significantly alter the peak current of NDIT. The practical application of the proposed DPAdSV procedure with the SPCE/SDS was successfully checked by analyzing spiked human serum samples.

Elaboration of novel urea bearing schiff bases as potent in vitro anticancer candidates with low in vivo acute oral toxicity

A novel series of urea Schiff base derivatives were synthesized via the condensation of o-phenylenediamine, naphthyl isocyanate and appropriate aryl aldehyde. The results of the in vitro cytotoxic activities of compounds 5a–h against cancer cells lines PC3, SKOV-3 and HeLa, revealed that almost all compounds exhibited good to moderate activities Compound 5g owing bromine atom at p-position displayed higher activity compared to homolog 5b possessing chlorine atom due to adequate diameter of bromine which is more favourable than chlorine for the inhibition activity. In addition, compound 5h is the best candidate of this series exhibiting excellent activity for three cancer cells lines. Compound 5h demonstrated also an excellent activity with IC50 value of 0.6±0.3μg/mL for prostate cancer cell line PC3 and it is considered more effective than the standard drug doxorubicin Dox (IC50 = 2.6±0.03μg/mL). The most active compound 5h displayed the best activity against ovarian cancer cell line SKOV3 with IC50 = 1.8±0.2μg/mL. This results are higher than clinically used drug Dox (IC50. 2.2±0.02μg/mL). The results of screening activities cytotoxic effect toward cervix cancer cell line HeLa, affirm that compound 5h manifest an activity with IC50 value of 2.2±0.4μg/mL comparable to Dox (IC50. 1.9±0.04μg/mL). In the current study, in vivo acute oral toxicity assessment of urea Schiff base hybrid compounds 5a – h indicated that there was no mortality on treated female mice during 14 days assessment test compared with the vehicle-treated group confirming the safety with LD50 greater than 2000 mg/kg. In the actual study, the results affirmed that compounds 5a–h manifested in vivo no toxicity to saint cells, the compounds 5b, 5g and 5h presented higher anticancer activities against three cancer cells which authorizes promoters to use them as candidate anticancer agents.

A Pyrazolate Osmium(VI) Nitride Exhibits Anticancer Activity through Modulating Protein Homeostasis in HepG2 Cells.

Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido complex Na[OsVI(N)(tpm)2] (tpm = [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol), which exhibited a greater inhibitory effect on the cell viabilities of the cervical, ovarian, and breast cancer cell lines compared with cisplatin. Proteomics analysis revealed that Na[OsVI(N)(tpm)2] modulates the expression of protein-transportation-associated, DNA-metabolism-associated, and oxidative-stress-associated proteins in HepG2 cells. Perturbation of protein expression activity by the complex in cancer cells affects the functions of the mitochondria, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it caused G2/M phase cell cycle arrest and caspase-mediated apoptosis of HepG2 cells. This study reveals a new high-valent osmium complex as an anticancer agent candidate modulating protein homeostasis.

Decoding mechanism of action and sensitivity to drug candidates from integrated transcriptome and chromatin state.

Omics-based technologies are driving major advances in precision medicine, but efforts are still required to consolidate their use in drug discovery. In this work, we exemplify the use of multi-omics to support the development of 3-chloropiperidines, a new class of candidate anticancer agents. Combined analyses of transcriptome and chromatin accessibility elucidated the mechanisms underlying sensitivity to test agents. Furthermore, we implemented a new versatile strategy for the integration of RNA- and ATAC-seq (Assay for Transposase-Accessible Chromatin) data, able to accelerate and extend the standalone analyses of distinct omic layers. This platform guided the construction of a perturbation-informed basal signature predicting cancer cell lines' sensitivity and to further direct compound development against specific tumor types. Overall, this approach offers a scalable pipeline to support the early phases of drug discovery, understanding of mechanisms, and potentially inform the positioning of therapeutics in the clinic.