Chemistry & Biodiversity

Ethanolic Fruit Extract of Piper Retrofractum Induced Cell Cycle Arrest, Apoptosis, Increased Reactive Oxygen Species Production, and Mitochondrial Dysfunction in Human Cervical Cancer

ABSTRACTCervical cancer remains a significant global health challenge, with high mortality rates and a pressing need for more effective therapeutic options. This study investigates the effects of an ethanolic extract from the fruit of Piper retrofractum (PR) on proliferation and apoptosis in cervical cancer cells. We evaluated the cytotoxicity of the crude ethanolic extract of PR using the sulforhodamine B and colony formation assay. Reactive oxygen species (ROS) generation, apoptosis, and mitochondrial function were quantified via flow cytometry. The effects on cell migration were assessed using wound healing and Transwell migration assays. The PR extract exhibited a significant inhibitory effect on HeLa cell viability, leading to reduced cancer cell proliferation. The extract induced cell cycle arrest at the G0/G1 phase in a dose‐dependent manner and decreased the proportion of cells in the G2/M phase at concentrations of 100 and 250 µg/mL. Additionally, treatment with the PR extract resulted in a marked increase in ROS production, disruption of mitochondrial function, and inhibition of cell migration. These findings suggest that the PR ethanolic fruit extract exerts substantial antiproliferative, antimigratory, and proapoptotic effects on HeLa cells. Consequently, the PR ethanolic fruit extract holds promise as a potential novel therapeutic agent for the treatment of cervical cancer.

Dual HER2/ERα Inhibitors for Breast and Ovarian Cancer: An Integrated Computational Study on 1,2,4‐Oxadiazole Derivatives

ABSTRACT The 1,2,4‐oxadiazole scaffold has attracted considerable interest as a privileged structure for anticancer drug development due to its favorable physicochemical properties and multimodal bioactivity. This study presents a comprehensive computational investigation to evaluate the potential of a series of 1,2,4‐oxadiazole derivatives as dual inhibitors of the human epidermal growth factor receptor 2 (HER2) and estrogen receptor alpha (ERα), two key drivers in these malignancies. An integrated in silico strategy was employed, combining density functional theory (DFT), molecular docking and dynamics simulations, pharmacokinetic profiling, and machine learning models. Our workflow identified several lead compounds exhibiting promising dual‐binding characteristics. Key derivatives demonstrated superior predicted binding affinity and complex stability compared to the reference inhibitor erlotinib. Pharmacokinetic evaluations indicated that the series possesses favorable drug‐likeness, with high predicted oral bioavailability and a low risk of cardiotoxicity. Furthermore, machine and deep learning models achieved robust performance in classifying compound activity, underscoring their utility in virtual screening. Collectively, this work validates the 1,2,4‐oxadiazole core as a promising scaffold for dual HER2/ERα inhibition and provides a rational, multi‐faceted computational blueprint. The identified lead compounds warrant subsequent experimental validation, and the established framework serves as a valuable template for accelerating the discovery of next‐generation targeted cancer therapies.

Synthesis of New Cinnamoyl‐Amino Acid Conjugates and in Vitro Cytotoxicity and Genotoxicity Studies

AbstractAmino acid conjugates are described by the reaction of amino acids with bioactive organic groups such as vitamins, hormones, flavonoids, steroids, and sugars. In this study, 12 new conjugates were synthesized by reaction of cinnamic acid derivatives with various amino acids. Cytotoxic studies against four different human cancer cells (MCF7, PC‐3, Caco‐2, and A2780) were carried out by MTT assay method at five different concentrations. The structure‐activity relationships based on the cell viability rates were evaluated. To compare the anticancer activities of the compounds using computational chemistry methods, they were docked against A2780 human ovarian cancer, Michigan Cancer Foundation‐7 (MCF7), human prostate cancer (PC‐3) and human colon epidermal adenocarcinoma (Caco‐2) cell lines and compared with the standard 5‐Fluorouracil. The results indicate that the efficacy of cinnamic acid derivatives increases with the presence of amino acids. Comet assay was conducted to understand whether the cell deaths occur through DNA damage mechanism and the results exhibit that the changes in the specified parameters were statistically significant (p<0.05). Our study demonstrated that the compounds cause cell death through the formation of DNA damage mechanism.

Divergent Synthesis, Antiproliferative and Antimicrobial Studies of 1,3‐Aminoalcohol and 3‐Amino‐1,2‐Diol Based Diaminopyrimidines

AbstractA series of novel diaminopyrimidines containing pinane moieties were synthesized via an efficient methodology starting from pinane‐based aminoalcohols, aminodiols and 2,4‐dichloropyrimidines. Bioassay tests demonstrated that compound 18a displayed much stronger antiproliferative activities against four human cancer cell lines (HeLa, Siha, MDA‐MB‐231, MCF‐7 and A2780) than positive control cisplatin. In particular, compound 22a was found to be selective in inhibiting HeLa cell proliferation with cancer cell growth inhibition values higher than 95 %. Moreover, the in vitro screening of prepared compounds against different bacterial and fungal strains is reported. The results revealed that 12b and 17a, the most promising compounds, displayed selective inhibition for the Gram‐positive bacteria (B. subtilis and S. aureus) with percent inhibition values ranging from 75 to 95 % at 10 μg/mL concentration. Both selective inhibition and the in vitro activity values demonstrated that these compounds have the potential to be developed into clinically important therapeutic choices for the treatment of infections caused by B. subtilis and S. aureus.

Cytotoxic Effect of the Essential oils from Erigeron Canadensis L. on Human Cervical Cancer HeLa Cells in Vitro

AbstractErigeron Canadensis L. (E. canadensis) is a widely distributed invasive weed species in China. Potentially anti‐cancer qualities may exist in its essential oils (EOs). The purpose of this study was to analyze the components of the EOs of E. canadensis and their effects on the normal liver cell lines L02 and the human cervical cancer cell lines HeLa. The EOs from the upper region of E. canadensis were prepared, its components were identified by GC/MS. Cell viability, cell morphology observation, AO/EB dual fluorescence staining assay, flow cytometry, mitochondrial membrane potential, western blot, caspase inhibitor test, and oxidative stress tests were used to investigate the impact of the EOs on HeLa cells. Network pharmacological analysis was employed to study the potential mechanism of the EOs in the treatment of cervical cancer. According to the findings, the EOs had 21 chemical components, of which limonene made up 65.68 %. After being exposed to the EOs, the cell viability of HeLa and L02 dramatically declined. The inhibition of EOs was more effective than that of limonene when used in an amount equivalent to that in the EOs. L02 cells were less susceptible to the cytotoxicity of EOs than HeLa cells were. Furthermore, EOs altered the cell cycle in HeLa cells and caused oxidative stress and apoptosis. Compared with the control group, the reactive oxygen species (ROS) levels increased in HeLa cells at first and then decreased, total superoxide dismutase (SOD) and catalase (CAT) activities in HeLa cells significantly decreased. G1 phase cells decreased whereas G2/M phase cells increased. The rate of apoptosis rose. Reduced mitochondrial membrane potential and Caspase‐3, −9, and −12 protein expression were both observed. Nerolidol, dextroparaffinone, and α‐pinene were shown to be the primary components for the suppression of HeLa cells, according to the results of the prediction of pharmacologic targets. In conclusion, findings of this study indicated the EOs may have the potential to curb the growth of cervical cancer cells. Further research is needed to explore the in vivo effect of EOs.

Evaluation of the Antiproliferative Potential of Eugenia pyriformis Leaves in Cervical Cancer Cells

AbstractEugenia pyriformis, typically known as uvaia, ubaia, uvaieira, uvalha or uvalha‐do‐campo, is a plant representative of the Myrtaceae family. E. pyriformis decreased HeLa cells proliferation, can induce cell death and reduce cell migration that may be related to metastasis and induction of cell death by apoptosis in vitro assays. Its leaves are used in folk medicine for hypertension control, decreased cholesterol and uric acid, slimming, astringent, and digestive. In this work, the evaluation of the in vitro anticancer potential Cervical Cancer (HeLa cells) and phytochemical analysis in E. pyriformes was performed. It was possible to quantify phenolic compounds and total flavonoids and identify Chlorogenic acid, Quercetrin, and Myricitrin in this species. The crude extract and ethyl acetate fraction inhibited cell viability by 50 % in the dose of 44.42 μg/mL and 40.39 μg/mL, respectively. The induced effector caspase 3/7 activation, which results in apoptosis and the ethyl acetate fraction, decreases cell migration of cancer cell lines; it is responsible for the cleavage of several cellular proteins that will result in the classic phenotype of the apoptotic cell.

GC‐MS/HPLC Profiling and Sono‐Maceration Mediated Extraction of Osbeckia Parvifolia Polyphenols: In Silico and In Vitro Analysis on Anti‐Proliferative Activity in Ovarian Cancer Cell Lines

AbstractOsbeckia parvifolia, an endemic edible plant of Western Ghats, was investigated in the present study for its polyphenolic compounds, including content, constituents, extraction through an ultrasonic‐assisted maceration technique and therapeutic potential in biomedical applications. The methanolic extract (OPM) exhibited an IC50 value of 1.25 μg/mL against 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH) radicals. Furthermore, the ethyl acetate and methanolic extracts also strongly inhibited 5‐lipoxygenase, especially OPM (84.93 %), which was comparable to standard curcumin. OPM also elicited cytotoxicity in SKOV3 ovarian cancer cells (93.80 %), surpassing paclitaxel. Bio‐accessibility analysis demonstrated that the release of phenolic compounds and antioxidant potential were very high (above 100 %), revealing the possibility of synergistic efficacy of polyphenolic complexes in drug development. Gas Chromatography ‐Mass Spectrometry (GC‐MS) analysis revealed 22 bioactive polyphenolic compounds in OPM, such as epicatechin, quercetin, and psoralidin. This was confirmed by High Performance Liquid Chromatography (HPLC) and High‐Pressure Thin Layer Chromatography (HPTLC) analyses, which revealed a high quantity of catechin (37.45 mg/g). Molecular docking revealed the significant binding affinity of these proteins for the ovarian oncoproteins PI3K (−8.52 kcal/mol) and Casp‐8 (−8.41 kcal/mol). Adsorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profiling indicated the favorable pharmacokinetic properties of these compounds, supporting their candidacy in drug formulations against ovarian cancer.

Phytochemical Profiling, Molecular Docking, and ER Stress‐Mediated Apoptosis Induced by Plantago loeflingii L. Essential Oil in Ovarian Adenocarcinoma Cells

ABSTRACT Plantago loeflingii L. (Plantaginaceae) is traditionally used for wound healing and tumor treatment, yet its cellular effects remain unexplored. This study provides the first integrated evaluation of its essential oil (PLA‐EO), including chemical composition, cytotoxicity, mechanistic assays, and molecular docking. Hydrodistillation followed by GC–MS/GC–FID identified 53 constituents (98.33%), dominated by linalool (23.81%), palmitic acid (15.34%), limonene (10.54%), thymol (8.51%), and α‐terpineol (5.23%). PLA‐EO selectively inhibited ovarian adenocarcinoma BG‐1 cells (IC 50  = 5.67 ± 0.6 µg/mL) while sparing MCF7, A549, and normal cells. Mechanistic assays revealed ER stress‐mediated apoptosis, as indicated by ER expansion, GRP78 upregulation, Ca 2 + overload, and caspase‐3 activation. To explore upstream triggers, molecular docking was performed against the EGFR kinase domain (PDB: 3W2S). The docking protocol was validated by redocking (RMSD = 0.98 Å), and erlotinib (−8.96 kcal/mol) reproduced known interactions with ASP855, ALA859, and PHE723. Palmitic acid (−9.05 kcal/mol) interacted with ARG836 via hydrogen bonding and hydrophobic contacts, while linalool (−7.17 kcal/mol) engaged ASP855 and PHE723. These interactions suggest possible EGFR modulation, though activity likely reflects synergistic contributions from multiple PLA‐EO components. In conclusion, PLA‐EO exhibits selective cytotoxicity in ovarian cancer cells via ER stress pathways, supported by in silico evidence of EGFR targeting. The combined phytochemical, cellular, and docking results highlight P. loeflingii as a promising source of bioactive essential oils, warranting further in vivo validation.

Methanol Extract of Young Lantana camara L. Leaves Exhibit Anti‐Ovarian Cancer and Anti‐Inflammatory Effects via Inhibition of PI3K/AKT/mTOR and MAPK Pathways

ABSTRACT Lantana camara (LC) L. is a widely distributed plant long used in African and Asian medicine for pain, inflammation, skin disorders, and cancer‐related symptoms. Young leaves are often brewed into teas to manage digestive and reproductive conditions, including ovarian inflammation. This study examined the methanol extract of young LC leaves for anti‐ovarian cancer and anti‐inflammatory potential through modulation of PI3K/AKT/mTOR and RAS/RAF/MEK/ERK (MAPK) pathways. Phytochemical and gas chromatography–mass spectrometry (GC–MS) analyses identified over 30 bioactive compounds, notably oleic acid, pyrazine, and palmitic acid. Anticancer activity was tested on SKOV3 and OVCAR‐3 ovarian cancer cells, with MTT assays showing strong cytotoxicity (IC 50 : 12.6 ± 1.8 and 18.9 ± 2.1 µg/mL), while sparing normal IOSE‐80 cells (IC 50  > 140 µg/mL). Annexin V‐FITC/PI staining indicated enhanced apoptosis, with early and late apoptotic populations reaching 31.4% ± 2.5% and 24.7% ± 3.1%. Western blot confirmed suppression of phosphorylated PI3K, AKT, mTOR, MEK, and ERK. In LPS‐stimulated RAW264.7 macrophages, the extract reduced nitric oxide, tumor necrosis factor‐alpha (TNF‐α) (−43.2%), interleukin (IL)‐6 (−39.8%), PGE2 (−47.6%), and cyclooxygenase‐2 (COX‐2) ( p  < 0.05). ELISA and immunofluorescence further validated cytokine inhibition. These results indicate that LC leaves possess strong anticancer and anti‐inflammatory properties, supporting their traditional use and therapeutic potential against ovarian cancer and inflammation.

Pyrazole, Pyrazoline, and Fused Pyrazole Derivatives: New Horizons in EGFR‐Targeted Anticancer Agents

AbstractPyrazole and its derivatives remain popular heterocycles in drug research, design, and development. Several drugs include the pyrazole scaffold, such as ramifenazone, ibipinabant, antipyrine, and axitinib, etc. They have been extensively studied by the scientific community and are said to have a wide range of biological activity, especially anticancer agents targeting EGFR. Overexpression of EGFR signalling promotes tumor growth by inhibiting apoptosis. EGFR dysfunction has been described in multiple cancers, including colon, head and neck, NSCLC, colon, liver, breast, and ovarian cancer. As a result, EGFR represents a prospective target for cancer treatment. Several anti‐EGFR drugs are thriving, notably dacomitinib, afatinib, erlotinib, gefitinib, and osimertinib. However, almost all currently available anti‐EGFR drugs have limited therapeutic effectiveness due to a lack of selectivity as well as substantial side effects. Furthermore, aberrant EGFR signalling across numerous human malignancies/carcinomas is impeded by gene amplification, protein overexpression, mutations, or in‐frame deletions, making EGFR‐induced cancer treatment challenging. To overcome such, novel therapeutic anti‐EGFR drugs with high efficacy and minimal toxicity are required. To battle cancer and therapeutic resistance to EGFR inhibitors, pyrazole, pyrazoline, and their derivatives have been investigated as a viable pharmacophore for the development of new drugs with better potency, lesser toxicity, and favourable pharmacokinetic characteristics. The present investigation covers the examination of progress toward anti‐cancer therapies targeting EGFR via pyrazole, pyrazoline, and fused pyrazole‐based compounds. The current study also represents inclusive data on pyrazole‐based marketed drugs as well as therapeutic candidates undergoing preclinical and clinical development. Lastly, we have discussed recent advances in the medicinal chemistry of pyrazole‐based derivatives with their anti‐EGFR significance for the eradication of various cancers and provide the direction toward structure‐activity relationship (SAR), including mechanistic studies.

Ferruginoside D: A Novel Phenylethanoid from Verbascum leiocarpum

AbstractA novel phenylethanoid, ferruginoside D, together with fourteen known compounds were isolated from the Verbascum leiocarpum for the first time. Chemical structures of isolated compounds were determined by spectroscopic analysis including HR‐ESI‐MS and NMR spectra. The antioxidant, α‐glucosidase inhibitory properties, and antiproliferative activities against multiple cell lines (A172, C6, HeLa, A2780, SW620, HT29, Beas2B, RPE, and HSF) of the isolated compounds were evaluated in vitro. According to the results, iridoids, flavonoids (luteolin and apigenin), and phenylethanoids (poliumoside and isoverbascoside) with strong antiproliferative potential were also found to have cytostatic effects. Furthermore, the investigation revealed that compounds luteolin, poliumoside, verbascoside, isoverbascoside, ferruginoside C, ferruginoside D, and ursolic acid show potent alpha‐glucosidase inhibitory activity, while compounds luteolin, verbascoside, and isoverbascoside exhibit substantial antioxidant activity. The new compound (ferruginoside D) was found moderately active against cancer cell lines, with strong alpha‐glucosidase inhibitory activity, and moderate antioxidant properties.

Two New Phenylpropanoids and a Polyphenol with Anti‐Cervical Cancer Activity from Smilax china L.

Abstract Two novel phenylpropanoids (compounds 1 and 2 ) and 11 known compounds were isolated from Smilax china L. Their structures were determined by NMR (1D and 2D) and high‐resolution electrospray ionization mass spectrometry. Further, the cytotoxic activity of all the isolated compounds against HeLa, 4T1, and U251 tumor cells was evaluated using the cell counting kit‐8 assay, revealing that compound 13 showed significant cytotoxicity toward HeLa cells. Further investigations explored the impact of compound 13 on the mitochondrial membrane potential, concentration of reactive oxygen species, wound‐healing distance, and cell cycle of HeLa cells. Notably, compound 13 significantly decreased mitochondrial membrane potential, suppressed cell migration, and increased intracellular reactive oxygen species levels in HeLa cells. Furthermore, compound 13 inhibited HeLa cell‐cycle progression in the S phase. These findings indicate that compound 13 is a potential drug lead for the treatment of cervical cancer.

A Novel Endophytic Fungus, Alternaria semiverrucosa , and Its Ethyl Acetate Extract Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells

ABSTRACT The present study aimed to identify the endophytic fungus ZZ‐HZ‐13 from Taxus chinensis var. marei and to investigate its biological activity. A novel species, Alternaria semiverrucosa (ZZ‐HJ‐13), was identified through morphological analysis combined with multigene phylogeny. The ethyl acetate extract (EAE) of A. semiverrucosa fermentation products demonstrated inhibitory effects on cervical cancer cells. Increasing concentrations of EAE caused marked morphological changes and higher inhibition rates in cervical cancer cells. After 48 h, the apoptosis rate of the cells significantly increased with increasing EAE concentration. In addition, the proportion of cells in the G 1 phase decreased, while the proportion in the G 2 phase increased significantly, indicating cell cycle arrest. Cell invasion and migration were also inhibited in a concentration‐dependent manner. Protein expression analysis revealed a significant upregulation of proapoptotic proteins, including Bax, cleaved caspase‐3, and cleaved caspase‐9, and of the cell cycle‐associated regulatory protein p21. Conversely, the expression levels of the antiapoptotic protein Bcl‐2 and the cell migration‐related proteins MMP1 and MMP9 were markedly decreased. In vivo experiments further demonstrated that EAE can suppress tumor growth in a mouse xenograft model. In conclusion, EAE derived from A. semiverrucosa demonstrates significant inhibitory effects on the proliferation of cervical cancer cells.

Transcriptome Analysis Reveals Possible Antitumor Mechanism of Intracellular Polysaccharide From Phaeodactylum tricornutum on Cervical Cancer HeLa Cells

ABSTRACT Seaweed polysaccharide, a naturally occurring, non‐toxic antitumor substance, has emerged as a significant focus of research. In this study, intracellular polysaccharides from Phaeodactylum tricornutum (PRP) were isolated and purified to investigate their antitumor effects and underlying mechanisms. The inhibitory effects of various purified polysaccharide fractions on cervical cancer cells were evaluated, and their antitumor mechanisms were elucidated through transcriptome analysis. The results demonstrated that all four purified polysaccharide fractions from P. tricornutum inhibited HeLa cell proliferation, reduced cell viability, and altered cell morphology. According to the cell counting kit‐8 (CCK‐8) assay, PRP4 exhibited the most potent inhibitory effect among the four fractions. Transcriptome analysis revealed 806 differentially expressed genes (DEGs) in the PRP4‐treated group compared to the control, comprising 570 up‐regulated and 236 down‐regulated genes. Gene function enrichment analysis indicated that DEGs were significantly enriched in apoptosis‐ and tumor‐related biological processes, implicating multiple cancer‐ and apoptosis‐associated signaling pathways. A protein–protein interaction (PPI) network identified 10 DEGs as hub genes, namely TLR4 , interleukin‐1β ( IL1B ), heme oxygenase‐1 ( HMOX1 ), EDN1 , PTGS2 , MMP9 , CXCL8 , TGFB1 , connective tissue growth factor ( CTGF ), and SERPINE1 . These findings suggest that PRP4 holds promise as a therapeutic agent for cancer treatment.

Cryptotanshinone Inhibits Obesity‐Related Cervical Cancer by Downregulating CXCL8 Expression in Hela Cells

ABSTRACT Cervical cancer is one of the cancers commonly found in the female reproductive system and is associated with obesity. However, the exact connection mechanisms remain unclear. Screening of key therapeutic targets and natural products with good antitumor activity has become a crucial strategy for cancer therapy. Cryptotanshinone is one of the main extracts of tanshinone, which has anti‐inflammatory and anti‐cancer properties. Key therapeutic targets and related low‐toxicity natural active ingredients were identified as crucial components in cancer treatment strategies. Therefore, network pharmacology and cellular biology techniques were used to screen and validate key targets in obesity‐related cervical cancer and to elucidate the mechanisms of its cryptotanshinone. The results indicated that C‐X‐C motif chemokine ligand 8 (CXCL8) might be modulated by cryptotanshinone. The knockdown of CXCL8 significantly reduced Hela cell viability to 15.29% ± 4.59% compared with the control group ( p  < 0.01), which consequently inhibited both cell proliferation and lipid droplet formation. Moreover, cryptotanshinone (20, 40, and 80 µM) significantly reduced CXCL8 expression and inhibited the NOD‐like receptor signaling pathway in Hela cells compared with the control group ( p  < 0.01). Therefore, this study manifested that cryptotanshinone potentially played an important role in obesity‐related cervical cancer. This study provided an important experimental basis for further exploring the pathogenesis and prevention of obesity‐related cervical cancer.

Investigation of the Apoptotic and Antimetastatic Effects of Nano‐Niosomes Containing the Plant Extract Anabasis setifera on HeLa: In Vitro Cervical Cancer Study

ABSTRACTThe present study focuses on the preparation of niosomes containing an extract of Anabasis setifera and evaluates their efficacy in inhibiting the growth and proliferation of HeLa cells. Thin‐layer hydration technique was used to prepare niosomes/extract nanoparticles (NPs). The physicochemical properties of the synthesized NPs were confirmed by scanning electron microscope (SEM), dynamic light scattering (DLS), zeta potential analysis, and FTIR. The cytotoxicity of the free extract, free niosome, and NPs was investigated by MTT (3‐(4, 5‐diMethylThiazol‐2‐yl)‐2,5‐diphenylTetrazolium bromide) assay. For this purpose, solutions of the three mentioned agents were prepared and diluted in 400, 200, 100, 50, 25, 12.5, and 6.25 µg/mL concentrations and incubated for 24, 48, and 72 h. After calculating the IC50 concentration and treating the cells with this concentration, real‐time polymerase chain reaction (PCR) (to measure changes in the expression of apoptosis and metastasis genes), flow cytometry (to determine the amount of early and late induced apoptosis), and cell cycle test (to determine the stopping stage of the cancer cell division cycle) were performed. Moreover, the scratch test (the ability to inhibit cell metastasis after treatment) was used to evaluate cell migration. The MTT assay results showed that 72 h of treatment with NPs has the greatest effect on the death of cancer cells. Real‐time PCR showed that the expression of the Bad gene increased dramatically and the expression of the BCL‐XL, integrin alpha 5 (ITGA5), and zinc finger E‐box‐binding homeobox 1 (ZEB‐1) genes decreased significantly. The flow cytometry results showed that 48.64% of HeLa cells underwent apoptosis after treatment with synthesized NPs. The scratch test results showed that cancer cell metastasis stopped after treatment with NPs. The research demonstrates the significant potential of plant extract‐loaded niosomes, as highly efficient drug carriers for cancer therapy.

Investigating the Antiproliferative Activity of Novel 4‐Chloro‐8‐Nitro‐1,2‐Dihydro‐3‐Quinoline Acylhydrazones on Human Cervical Cancer Cell Lines

AbstractA new series of acyl hydrazones have been synthesized from 4‐chloro‐8‐nitro‐1,2‐dihydroquinoline‐3‐carbaldehyde. These compounds were characterized using various spectroscopic techniques. Density functional theoretical (DFT) studies were conducted to understand the correlation between electronic parameters and biological activity. The biological activity of the compounds was theoretically examined through molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis. The compounds demonstrated high absorption rates and were found to be non‐hepatotoxic. Preliminary cytotoxicity screenings against HeLa cell lines identified compound 7 as the most potent, with an IC50 value of 18.8 μM. This compound was further selected for bioimaging studies. The results indicate that compound 7 induces apoptosis at its IC50 concentration, suggesting its potential as an anticancer agent.

Analysis of Quinolinequinone Analogs with Promising Cytotoxic Activity against Breast Cancer

AbstractIt is quite challenging to find out bioactive molecules in the vast chemical universe. Quinone moiety is a unique structure with a variety of biological properties, particularly in the treatment of cancer. In an effort to develop potent and secure antiproliferative lead compounds, five quinolinequinones (AQQ1‐5) described previously have been selected and submitted to the National Cancer Institute (NCI) of Bethesda to envisage their antiproliferative profile based on the NCI Developmental Therapeutics Program. According to the preliminary in vitro single‐dose anticancer screening, four of five quinolinequinones (AQQ2‐5) were selected for five‐dose screening and they displayed promising antiproliferative effects against several cancer types. All AQQs showed a excellent anticancer profile with low micromolar GI50 and TGI values against all leukemia cell lines, some non‐small cell lung and ovarian cancer, most colon, melanoma, and renal cancer, and in addition to some breast cancer cell lines. AQQ2‐5 reduced the proliferation of all leukemia cell lines at a single dose and five additional doses, as well as some non‐small cell lung and ovarian cancer, the majority of colon cancer, melanoma and renal cancer, and some breast cancer cell lines. This motivated us to use in vitro, in silico, and in vivo technologies to further investigate their mode of action. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ3, in HCT‐116 colon cancer, MCF7 and T‐47D breast cancer, and DU‐145 prostate cancer cell lines, and HaCaT human keratinocytes. Concomitantly, IC50 values of AQQ2 and AAQ3 against MCF7 and T‐47D cell lines of breast cancer, DU‐145 cell lines of prostate cancer, HCT‐116 cell lines of colon cancer, and HaCaT human keratinocytes were determined. AQQ2 exhibited anticancer activity through the induction of apoptosis and caused alterations in the cell cycle. In silico pharmacokinetic studies of all analogs have been carried out against ATR, CHK1, WEE1, CDK1, and CDK2. In addition to this, in vitro ADME and in vivo pharmacokinetic profiling for the most effective AAQ (AAQ2) have been studied.

Evaluation of the Antiproliferative Potential of Yellow Jaboticaba (Myrciaria glazioviana) Extracts Against Human Cervical Cancer (HeLa cells line) and the Analysis of Their Chemical Composition by HPLC‐HRESIMS

AbstractCervical cancer is a specific type of cancer that affects women around the world, with an incidence of 604 thousand new cases per year and 341 thousand deaths. There is a high demand for new effective antineoplastic drugs with few side effects. In this sense, recent research highlights the potential of compounds of natural origin in treating and preventing different types of cancer. Myrciaria glazioviana is a Brazilian native species belonging to the Myrtaceae family, which has previously described biological activities such as antimicrobial, anti‐inflammatory, and antioxidant properties. This study aims to evaluate the anticancer activity of the dichloromethane extract (MGD) and ethyl acetate extract (MGA) of M. glazioviana leaves against human cervical cancer cell line (HeLa), as well as to identify their bioactive compounds. Using HPLC‐HRESIMS technique, ten compounds were characterized in both samples: quinic acid, ellagic acid, Tri‐O‐methyl ellagic acid, two derivatives of Tetra‐O‐methyl flavellagic acid, quercetrin, Di‐O‐methyl ellagic acid, and three derivatives of pentamethyl coruleoellagic acid. Through MTT assays using HeLa cells and NIH/3T3 cells, it was observed that MGD and MGA were selective against tumor cells, with IC50 values of 24.31 and 12.62 μg/mL, respectively. The samples induced the tumor cell death by apoptosis, as evidenced by the activation of caspases 3/7, cell shrinkage, and pyknotic nuclei. Both samples were also able to inhibit the migration of HeLa cells after 24 hours of treatment, indicating a potential antimetastatic effect. Therefore, the present research highlights the antiproliferative and antimigratory potential of this species against HeLa cells.

Synthesis, Biological Evaluation and Action Mechanism Study of New Mitochondria‐Targeted Curcumin Derivative as Potential Antitumor Drugs

AbstractMitochondria have emerged as important targets in cancer therapy due to their key role in regulating energy supply, maintaining redox homeostasis, and intrinsic apoptosis. Curcumin (CUR) has shown promise in inhibiting the proliferation and metastasis of cancer cells by inducing apoptosis and arresting cell cycle. However, the clinical application of CUR has been limited by its low stability and poor tumor selectivity. To address these issues, the novel mitochondria‐targeted curcumin derivatives were synthesized through the unilateral coupling (CUR‐T) or bilateral coupling (CUR‐2T) of curcumin's phenolic hydroxy groups with triphenyl phosphorus via ester bond. The aim was to achieve better stability, higher tumor selectivity, and stronger curative efficacy. The results of stability and biological experiments indicated that both stability and cytotoxicity were arranged in descending order of CUR‐2T>CUR‐T>CUR. In ovarian cancer cells (A2780 cells), CUR‐2T showed well‐defined preferential selectivity towards cancer cells and exhibited efficient anticancer efficacy due to its superior mitochondria accumulation ability. Subsequently, the mitochondrial redox balance was disrupted, accompanied by increased ROS levels, decreased ATP levels, dissipated MMP, and increased G0/G1 phase arrest, leading to a higher apoptotic rate. In summary, the results of this study suggest that CUR‐2T holds substantial promise for further development as a potential agent for the treatment of ovarian cancer.