Normal Vero Cells Research Articles

Substituent Effect on Cytotoxicity and Interaction Profile of DNA/BSA With Selected Terpyridine Derivatives of Ester/Ferrocene and Their Fe(III) and Ru(III) Complexes—A Comparative Analysis

ABSTRACTThe present work demonstrates the synthesis of ester and ferrocene groups containing new terpyridine‐based ligands (FRL and RL) and their selected meal complexes FR‐Fe, FR‐Ru, RL‐Fe, and RL‐Ru. Investigations on the influence of the ester and ferrocene groups on binding to DNA/BSA and anticancer activity were carried out. All these products were structurally characterized by using spectroscopic and analytical techniques. Notably, the molecular structures of both the ligands and the ester‐based Fe(III) complex were confirmed by single‐crystal X‐ray diffraction analysis. Additionally, theoretical calculations were employed to further establish the structures of the synthesized ligands and their metal complexes, which were subsequently utilized for molecular docking studies to evaluate their binding potential. The docking results revealed the best binding orientation with the lowest possible binding energy of −10.20 kcal/mol for the RL‐Fe complex with BSA and −8.30 kcal/mol for the FR‐Fe complex with DNA. Furthermore, the binding interactions of all the synthesized compounds were investigated using UV–visible absorption (UV) and fluorescence spectroscopy (FL). The binding sites and binding constants were determined using the Stern‐Volmer equation. Moreover, cytotoxicity assays were performed against lung cancer (A549), liver cancer (Hep G2), and normal Vero cell lines, with results benchmarked against cisplatin. Notably, the ligand (FRL) exhibited significant cytotoxic action with an IC50 of 54.51 μM compared to the related Fe(III) complex (FR‐Fe) (i.e., 69.86 μM) against A549 cells. But the complex FR‐Fe displayed IC50 of 56.19 μM against Hep G2 cells, demonstrating better potency over cisplatin.

Dual VEGFR-2 and EGFRT790M inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis.

New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized. Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFRT790M (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors. Derivative 14 was the most active on A549, HCT116, HepG2, and MCF-7 cancers with half-maximal inhibitory concentration (IC50) = 5.50, 9.77, 7.12, and 7.85 µM respectively. The assessed derivatives 5, 7, 8, 9, 10, 12 and 14 showed IC50 = 54.40-62.60 μM against normal VERO (normal kidney) cells with low toxicity. In addition, derivatives 14, 8, 10, 7 and 9 were discovered to be very good active inhibitors of VEGFR-2 at IC50 values of 1.15, 1.35, 140, 1.78 and 1.90 µM, respectively. Furthermore, derivatives 14, 10, 8, and 9 strongly repressed EGFRT790M with IC50 = 0.28, 0.33, 0.35, and 0.50 µM correspondingly. Additionally, the highly active compounds 8, 10, and 14 showed good ADMET profile. Our derivatives could be considered as anticancer agents with dual VEGFR-2 and EGFRT790M inhibition.

Development of a Novel Peptide with RGD Tumor Homing Motif: Evaluation of its Anticancer Potential in Hepatocellular Carcinoma and Colon Cancer Cells

Background: Peptide-based therapy has emerged as a promising avenue for treating various disorders, and recent research has highlighted the potential of anti-cancer peptides (ACPs) in cancer treatment. In this context, this study aimed to design a novel peptide incorporating a tumor-homing peptide (RGD) and C-amidation to enhance its anticancer activity, particularly against liver (HepG2) and colon (HCT-116) cancer cell lines. Objectives: The primary objective was to design a peptide with improved anticancer properties by leveraging the tumor-homing capabilities of RGD and enhancing its activity through C-amidation. The study sought to evaluate the cytotoxicity of the designed peptide against red blood cells (RBCs) and normal Vero cells. Furthermore, the anticancer efficacy of the peptide was assessed in hepatocellular carcinoma (HepG2) and colon cancer (HCT-116) cell lines. The specific objectives included examining the apoptotic induction and morphological changes in treated cells compared to untreated cells. Methods: The peptide was designed using the ACPred-FL bioinformatics tool, and its cytotoxicity was assessed through hemolysis assays against RBCs and normal Vero cells. Anticancer activity was evaluated against HepG2 and HCT-116 cell lines. The analysis of apoptotic induction involved measuring the relative gene expression of oncogenic marker BCL2 and apoptotic markers (BAX, BID, CAS-8). Additionally, Cytopathological examination and Western Blot analysis were employed to study morphological changes and confirm the quantification of relevant markers. Results: The designed peptide, consisting of twelve amino acids with a molecular mass of 1230.6233 Da and an isoelectric point of 9.81, exhibited low erythrocyte lysis and minimal toxicity to normal cells. The IC50 values demonstrated significant anticancer activity against both HepG2 (36.49±2.6 μg/mL) and HCT-116 (11.03±2.5 μg/mL) cell lines. Treated cells exhibited a significant decrease in the oncogenic marker BCL2 and an upregulation of apoptotic markers (BAX, BID, CAS-8). Western Blot analysis confirmed these results in addition to cytopathological examination that scattered apoptotic and degenerative changes. Conclusion: The designed peptide is considered a patent product that displayed remarkable anticancer activity against hepatocellular carcinoma and colon cancer cell lines, effectively modulating apoptotic and oncogenic markers. These findings highlight the potential of the peptide as a therapeutic agent for cancer treatment, emphasizing its clinical significance in combating liver and colon cancers. Nonetheless, further research and development are warranted to explore the translational potential of this peptide in clinical studies.

Evaluation the Medicinal Potential of <i>Phallus indusiatus</i> as a Protein-Rich Source for Applications in Meat Analogs

This study investigates the medicinal potential of proteins derived from Phallus indusiatus, commonly known as bamboo mushroom, focusing on their bioactive properties of the mushroom proteins, including antioxidant, anticancer and anti-inflammatory effects. Using a non-solvent extraction method, crude proteins were isolated and purified through anion-exchange chromatography. After stepwise NaCl elution, distinct eluted peaks were collected, designated P1-P4 fraction. Each purified protein fractions primarily demonstrated moderate antioxidant activity. Bioactivity assessments were further conducted on several protein fractions (P1, P2, P3, and P4) using LPS-stimulated RAW264.7 cells to evaluate their anti-inflammatory properties. The results revealed that proteins P1, P3, and P4 significantly reduced nitric oxide production, with P4 demonstrating the most potent effect. As the results, P1, P3, and P4 would be exhibited as Fungal Immunomodulatory Proteins (FIPs) with selective anti-inflammatory activity, suggesting their potential for further therapeutic applications. Anticancer activity was assessed against A549, where all protein fractions exhibited notable cytotoxicity against cancer cell, without affecting normal Vero cells. These findings highlight the potential of P. indusiatus proteins containing pharmacological properties for developing mushroom-based meat analogs.

Biosynthesis of novel MnO<SUB>2</SUB> nanocapsules via <I>C. spinosa</I> extract and honeybee-derived chitosan: exploring antibacterial and anticancer properties

This investigation delves into the integration of Capparis spinosa extract (CSLe) onto manganese dioxide nanoparticles (MnO2NPs) and chitosan derived from honeybees (CSH) in a nanostructured configuration. The resultant nanocomposites, namely CSLe@MnO2NPs and CSH/CSLe@MnO2NPs, underwent thorough characterization through various analytical techniques. UV-Vis spectroscopy unveiled distinctive features, such as ligand-to-metal charge transfer and photoluminescence, affirming the successful chitosan-functionalization of the MnO2NPs, thereby differentiating them from their pristine counterparts. FTIR spectra corroborated the binding of chitosan and identified crucial molecular functional groups. SEM-EDX analysis revealed the morphological properties, addressing non-uniform sizes in the as-calcined MnO2NPs by the uniform coating of CSH on CSLe@MnO2NPs, while EDX confirmed the presence of essential elements. TEM and SAED provided insights into the spherical morphology, crystalline structure, and lattice planes of these nanoparticles. Size distribution measurements highlighted distinctions between CSLe@MnO2NPs and CSH/CSLe@MnO2NPs. The nanomaterials underwent evaluation for their antimicrobial properties against a spectrum of Gram-negative and Gram-positive bacterial strains, with CSH/CSLe@MnO2NPs exhibiting the highest bactericidal activity. Additionally, they demonstrated low minimum inhibitory concentration (MIC) values, especially against S. aureus (MIC as low as 12.5 µg/ml). Their efficacy extended to anti-biofilm formation, significantly diminishing biofilm development in a dose-dependent manner, a pivotal factor in addressing biofilm-related infections. The study also scrutinized their cytotoxicity against normal Vero and PC3 prostate cancer cells, revealing potential anticancer properties. Dose-dependent reductions in cell viability were observed for both normal and cancer cells. In conclusion, these findings underscore the versatility and promise of CSH/CSLe@MnO2NPs in diverse biomedical applications, including antibacterial, anti-biofilm, and anticancer therapies.

Phytochemical study and biological activity of Morettia philaeana (Delile) DC

Morettia phillaeana (Delile) DC. (family Brassicaceae) is used in Sudan traditionally to treat some skin and digestive tract diseases. The aim of this study was to investigate the chemical profile of the root, stem, leaf, flower and fruit of M. phillaeana and to evaluate their cytotoxicity, antibacterial, antigiardial, antimalarial and antioxidant activities. Extracts were prepared by sequential maceration of powder of each organ in acetone and methanol. Cytotoxicity was tested against normal Vero cell line. Antibacterial activity was determined by the disc diffusion method. Antimalarial and antigiardial activities were determined by microplate assay against the K1 parasite strain of Plasmodium falciparum and Giardia duodenalis respectively. The DPPH and ABTS assays were adopted to evaluate the antioxidant activity. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, steroids, terpenes and saponins as metabolites. The stem, fruit and leaf accumulated the highest total phenolic (3903.85 GAE mg/g), flavonoids (1078.37 mg QE/g) and tannins (1009.05 TAE mg/g) contents respectively. Results of biological activity revealed that the plant possessed mainly significant antigiardial and antibacterial activities. The highest antigiardial effect was recorded from the acetone and ethanol extracts of the leaf (IC50 4.40 and 4.49 and µg/mL, p ≥ 0.05) and the highest antibacterial activity was obtained against Escherichia coli from the ethanolic extracts of leaf (inhibition zone = 23.2 mm). The acetone extract of the fruit displayed moderate ABTS radical scavenging activity (66.7 %). All organs’ extracts exerted weak antimalaria activity (IC50 172.2–238.5 µg/mL). All extracts, except the acetone extract of the stem (IC50 43.48 µg/mL), were not toxic (IC50 ≥ 222.09 µg/mL). In conclusion, it is worth mentioning that the present study demonstrates for the first time the cytotoxicity, antigiardial and antimalarial properties of M. phillaeana and the results obtained partly supported its traditional uses. The plant could be a promising source of bioactive molecules for different pharmaceutical applications.

The Influence of New Antitumor Compounds Based on Azoloazine Derivatives on Level of DNA Damage in Normal Vero Cell Line in the DNA Comet Assay

The Influence of New Antitumor Compounds Based on Azoloazine Derivatives on Level of DNA Damage in Normal Vero Cell Line in the DNA Comet Assay

Green synthesis of Brassica carinata microgreen silver nanoparticles, characterization, safety assessment, and antimicrobial activities

Nanotechnology has been a central focus of scientific investigation over the past decades owing to its versatile applications. The synthesis of silver nanoparticles (AgNPs) through plant secondary metabolites is a cost-effective and eco-friendly approach. The present study employed Brassica carinata microgreen extracts (BCME) to promote the reduction of silver nitrate (AgNO3) salt into Brassica carinata microgreen silver nanoparticles (BCM-AgNPs). The physicochemical properties of the biosynthesized AgNPs were characterized through both spectroscopy and microscopy techniques. Furthermore, the antimicrobial property of the biosynthesized AgNPs was assessed against six selected pathogenic microorganisms, and finally, their safety was evaluated on a normal Vero cell line through an MTT cytotoxicity assay. The UV-visible spectrum revealed that BCM-AgNPs exhibited an absorption peak at 420 nm. The potential functional groups involved in the biosynthesis of AgNPs were identified by Fourier transform infrared (FTIR) analysis. Scanning electron microscopy (SEM) revealed a spherical nature of the biosynthesized AgNPs. Transmission electron microscopy (TEM) analysis revealed the crystallinity of the AgNPs, averaging 34.68 nm in size. X-ray diffraction (XRD) investigation further confirmed the crystalline structure of the AgNPs. The zeta potential exhibited a significant value of − 22.5 ± 1.16 mV. Regarding the antimicrobial potential, BCM-AgNPs exhibited promising antimicrobial activity against the tested pathogens, with a minimum inhibitory concentration (MIC) of 62.5 µg/mL observed in Pseudomonas aeruginosa. Further cytotoxicity assessment of BCM-AgNPs conducted on Vero cells demonstrated their safety. This study presents a novel approach to synthesizing AgNPs using a nutraceutical microgreen, offering a biocompatible and promising alternative for combating multi-drug resistance.

Innovative anti-proliferative effect of the antiviral favipiravir against MCF-7 breast cancer cells using green nanoemulsion and eco-friendly assessment tools

Telomerase enzyme prevents telomere shortening during division, having human telomerase reverse transcriptase (hTERT) as its catalytic subunit. Favipiravir (FAV), an RNA-dependent RNA polymerases inhibitor, shared structural similarity with hTERT and thus assumed to have cytotoxic effect on cancer cells, in addition to its prophylactic effect to immunocompromised cancer patients. Nanoemulsion (NE) is a potential tumor cells targeting delivery system, thereby enhancing therapeutic efficacy at the intended site, mitigating systemic toxicity, and overcoming multidrug resistance. The objective of this study is to develop a green FAV nanoemulsion (FNE) that is environmentally friendly and safe for patients, while aiming to enhance its cytotoxic effects. The study also highlights the environmental sustainability of the developed RP-HPLC method and assesses its greenness impact. The FNE formulation underwent thermodynamic stability testing and invitro characterization. Greenness was assessed using advanced selected tools like the Analytical Eco-Scale (AES), Analytical Greenness Metric for Sample Preparation (AGREEprep), and green analytical procedure index (GAPI). The cytotoxic potential of FNE was screened against MCF-7 breast cancer and Vero normal cell lines using SRB assay. Stable and ecofriendly FNE was formulated having a particle size (PS) of 25.29 ± 0.57 nm and a zeta potential of -6.79 ± 5.52 mV. The cytotoxic effect of FNE on MCF-7 cells was more potent than FAV with lower IC50 while FNE showed non-toxic effect on VERO normal cell line. Therefore, the FAV nanoemulsion formulation showed targeted cytotoxicity on MCF-7 cells while being non-toxic on normal Vero cells.

Evaluation of Xanthone and Cinnamoylbenzene as Anticancer Agents for Breast Cancer Cell Lines through In Vitro and In Silico Assays

Breast cancer is a severe global disease for women as the number of deaths increases annually. Therefore, attempts to find new anticancer agents are critical and inevitable. In this work, we report the investigation on the anticancer activity of xanthone and cinnamoylbenzene compounds against two breast cancer cell lines, i.e., T47D and MCF-7, through experimental in vitro and theoretical in silico assays. Xanthone and cinnamoylbenzene exhibit anticancer activity with a half-maximal inhibitory concentration (IC50) of 136.7–194.3 and 235.8–262.4 µg/mL against T47D and MCF-7 cancer cells, respectively. Cinnamoylbenzene generates less cytotoxicity to normal Vero cells with a selectivity index of 1.095–2.102. The molecular docking studies agree with the experimental data in which cinnamoylbenzene is more active against T47D with an IC50 of 136.7 µg/mL due to Topoisomerase II inhibition through π-π stacked interactions with Adenine12 and Guanine13 nitrogen bases. Meanwhile, xanthone is more active against MCF-7 with an IC50 of 235.8 µg/mL due to EGFR inhibition through van der Waals interaction and hydrogen bond with Glutamic acid767 and Methionine769 amino acid residues, respectively. Additionally, the pharmacokinetic parameters of xanthone and cinnamoylbenzene are predicted through absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, and they show better suitability than doxorubicin as the commercial anticancer drug.

Tridentate N-donor Schiff base metal Complexes: Synthesis, Characterization, computational Studies, and assessment of biomedical applications in cancer Therapy, Helicobacter pylori Eradication, and COVID-19 treatment

A unique Schiff base ligand (BCA), 4-(2-((1E,2E)-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazinyl)quinazoline, was synthesized and complexed with Mn [II], Co [II], Cu [II, and Cd [II] ions, with 1,10-Phenanthroline (PHN) as an auxiliary ligand. The unique Schiff base ligand BCA and its metal complexes were characterized using multiple analytical techniques, including elemental analysis, UV–visible spectroscopy, FT-IR, mass spectrometry, and conductometric measurements. These methods provided detailed insights into the compounds’ structural and electronic properties. Density Functional Theory (DFT) computations complemented the experimental data, elucidating electronic configuration stability, HOMO-LUMO energy gaps, chemical hardness, and dipole moments. The computational results confirmed the distorted octahedral structure of the complexes. Antimicrobial testing against various bacterial and fungal strains revealed that the Cd (II) complex exhibited the highest activity, with inhibition zones ranging from 19.7 ± 0.6 mm to 35.0 ± 1.0 mm, surpassing the activity of standard antibiotics in some cases. Notably, the compounds displayed significant efficacy against Helicobacter pylori, with the Cd (II) complex showing an inhibition zone of 32.67 ± 0.58 mm and a minimum inhibitory concentration (MIC) of 7.8 μg/ml. Anticancer properties were evaluated against MCF-7 (Breast carcinoma) cells, with the [(BCA)(PHN)Cd(H2O)].2Cl·2H2O complex demonstrating superior activity (IC50 = 29.97 μg/ml) compared to the free ligand (IC50 = 183.96 μg/ml) and other metal complexes. Notably, the Cd(II) complex showed reduced cytotoxicity towards normal VERO cells, suggesting potential selectivity for cancer cells. Molecular docking simulations evaluated the complexes’ binding interactions with protein targets associated with Helicobacter pylori, MCF cancer cells, and the COVID-19 virus. The main objective of this research was to design and synthesize a unique Schiff base ligand and its new corresponding Ternary metal complexes and then investigate their potential medical applications. Specifically, the study aimed to evaluate the compounds’ effectiveness as antibiotics, antitumor agents, and possible treatments for COVID-19.

New naphtho[2,1-b]furan-2,5-dione and isocoumarin derivatives from bambusicolous fungus Gelatinomyces siamensis

Two new compounds, 6-hydroxy-1-(4-hydroxyphenyl)naphtho[2,1-b]furan-2,5-dion (1) and 3-methyl-6-α-L-rhamnopyranosyl-2H-chromen-2-one (2), along with three known compounds (3-5) were isolated from the rare bambusicolous fungus Gelatinomyces siamensis. The structures were elucidated through the analysis of IR, NMR and HRESIMS spectrographic data. Compound 1 exhibited cytotoxicity against HeLa, HT29, MCF-7 and PC-3 cells, but was not toxic against normal Vero cells. The most abundant metabolite, oosporein (5), exhibited significant cytotoxic effects against all tested cancer cells.

Aspergillus fumigatus-induced biogenic silver nanoparticles' efficacy as antimicrobial and antibiofilm agents with potential anticancer activity: An in vitro investigation

A worldwide hazard to human health is posed by the growth of pathogenic bacteria that have contaminated fresh, processed, cereal, and seed products in storage facilities. As the number of multidrug-resistant (MDR) pathogenic microorganisms rises, we must find safe, and effective antimicrobials. The use of green synthesis of nanoparticles to combat microbial pathogens has gained a rising interest. The current study showed that Aspergillus fumigatus was applied as a promising biomass for the green synthesis of biogenic silver nanoparticles (Ag NPs). The UV–visible spectra of biosynthesized Ag NPs appeared characteristic surface plasmon absorption at 475 nm, round-shaped with sizes ranging from 17.11 to 75.54 nm and an average size of 50.37 ± 2.3 nm. In vitro tests were conducted to evaluate the antibacterial, antioxidant, and anticancer effects of various treatment procedures for Ag NP applications. The synthesized Ag NPs was revealed antimicrobial activity against Aspergillus flauvas, A. niger, Bacillus cereus, Candida albicans, Esherichia coli, Pseudomonas aerugonosa, and Staphylococcus aureus under optimum conditions. The tested bacteria were sensitive to low Ag NPs concentrations (5, 10, 11, 8, 7, 10, and 7 mg/mL) which was observed for the mentioned-before tested microorganisms, respectively. The tested bacterial pathogens experienced their biofilm formation effectively suppressed by Ag NPs at sub-inhibitory doses. Antibacterial reaction mechanism of Ag NPs were tested using scanning electron microscopy (SEM) to verify their antibacterial efficacy towards S. aureus and P. aeruginosa. These findings clearly show how harmful Ag NPs are to pathogenic bacteria. The synthesized Ag NPs showed antitumor activity with IC50 at 5 μg/mL against human HepG-2 and MCF-7 cellular carcinoma cells, while 50 mg/mL was required to induce 70 % of normal Vero cell mortality. These findings imply that green synthetic Ag NPs can be used on cancer cell lines in vitro for anticancer effect beside their potential as a lethal factor against some tested pathogenic microbes.

Modified release, enriched biocompatibility, and enhanced oral bioavailability as precious features of nitrofurantoin-loaded polymeric nanoparticles

Nitrofurantoin (NTF) is a first-line therapy for treating urinary tract infections. However, gastric upset, short half-life, and poor bioavailability of NTF are major challenges for clinical use. Hence, the current work incorporated NTF in polymeric nanoparticles (NPs).NTF-loaded NPs (NTF-NPs) were prepared using Eudragit RS100 (RS100), DL-lactide/glycolide copolymer (PLGA), and their mixture at a ratio of 1:1 w/w (RS100/PLGA) as polymers. Pluronic F68, Tween 80, and polyvinyl alcohol (PVA) were applied as stabilizers. The particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency were determined. Three optimized formulations of NPs; F3, F13, and F29 were selected for further coating with Eudragit L100 (L100) and Eudragit S100 (S100). The optimized NPs and the corresponding coated ones were evaluated for solid-state characterization, morphology, and in vitro release. L100-coated F13 (LCF13) was further investigated for biocompatibility with normal oral epithelial cell (OEC) and Vero cell lines. A pharmacokinetic study using a rat model was also conducted.The results revealed that Tween 80 and PVA-stabilized NPs accomplished a nano-sized range with polymer- and stabilizer-dependent PDI and ZP. Optimized formulations: F3, F13, and F29 were selected for further coating where PS and PDI values not exceeding 260 nm and 0.502, respectively. The coated NPs had negative ZP ranging from −11.00 ± 2.70 to −40.20 ± 1.40 mV, attributable to the L100 or S100 coating. The solid-state characterization confirmed a transition of NTF to amorphousness. The spherical shape with the distinctive halo-like appearance of the coated NPs was proved. Additionally, the coating warranted a prolonged release of NTF especially for LCF13 avoiding the burst effect. Allowing enriched biocompatibility, LCF13 showed an IC50 value of 224.00 ± 9.20 μM for the OEC cell line, whereas a greater IC50 exceeding 300 μM was recognized for the LCF13-treated Vero cell line. After a single oral dose, LCF13 could provide a discernible increase in the extent of absorption (Du∞ = 863.31 ± 73.71 μg) with a significant extension of the absorption rate (tmax and t1/2 of 3 and 2.51 ± 0.317 h, respectively).LCF13 could be considered a controlled and safe nanocarrier that delivered significantly higher levels of NTF for a longer duration than NTF dispersion.

Exploring Label-Free Imaging Techniques with Copper Sulfide Microspheres for Observing Breast Cancer Cells.

A single breast cancer is a prevalent form of cancer, affecting over 2.3 million women worldwide, as reported by the World Health Organization. Recently, researchers have extensively explored the utilization of biomaterials in breast cancer theranostics. One notable biomaterial being investigated is various structures of copper sulfide (CuS). In this work, a microsphere (MS) structure composed of CuS was employed for label-free imaging of MCF-7 breast cancer cells and normal Vero cells, respectively. Various label-free imaging techniques, such as bright field, dark field, phase contrast (PC), and differential interference contrast (DIC), were employed to capture images of CuS MSs, cell, and intact CuS MSs within a cell. The study compared the outcomes of each imaging technique and determined that DIC imaging provided the highest resolution for cells incubated with CuS MSs. Furthermore, the combination of PC and DIC techniques proved to be effective for imaging breast cancer cells in conjunction with CuS MSs. This research underscores the potential of CuS MSs for label-free cell detection and emphasizes the significance of selecting appropriate imaging techniques to attain high-quality images in the field of cell observation.

Phytochemical characterization, biochemical profiling and evaluation of anticancer potential of methanolic extract of Withania somnifera stem.

Phytotherapy employs phytoconstituents/phytomedicines derived from plants for treating and preventing illnesses. Withania somnifera is known in the Indian Ayurveda Pharmacopoeia for its medicinal applications and pharmacological properties. In this study, we examined the biological activity spectrum of Withania somnifera methanolic extract of stem (WSME), which is valued as a "Rasayana" due to its extensive range of medicinal uses. WSME was subjected to TPC and TFC quantification and bioactive components were characterized using LC-MS. Its antioxidant potential was gauged by DPPH and H2O2 radical scavenging assays, while antibacterial efficacy was assessed against S.aureus and E.coli using disc diffusion assay. In vitro anticancer activity was evaluated against human breast cancer MDA-MB-231 cells while toxicity was evaluated against normal Vero cells using MTT assay. WSME, rich in Withaferin A, showed TPC of 4.73±0.15 mg GAE/g and TFC of 94.94±6.15 mg QE/g dry weight of extract. It exhibited significant antioxidant activity (43.28 and 66.8 % inhibition at 1,000 μg/mL using DPPH and H2O2 assays, respectively) and mild antibacterial effects against S.aureus (300-500 mg/mL). WSME induced cell death in MDA-MB-231 cells and significantly inhibited their growth (IC50: 66 μg/mL, P value<0.05) without affecting normal Vero cells in the studied range of 25-400 μg/mL (IC50: 6.09 mg/mL, P value>0.05). The present study lends support to further testing of WSME against other cancer cell lines and animal models of cancer. These preclinical studies would provide further validation to its prospective use as an adjunct in human breast cancer therapy.

Novel benzenesulfonamides as dual VEGFR2/FGFR1 inhibitors targeting breast cancer: Design, synthesis, anticancer activity and in silico studies

In the current study, a new series of benzenesulfonamides 6a-r was designed and synthesized as dual VEGFR-2 and FGFR1 kinase inhibitors with anti-cancer activity. The 4-trifluoromethyl benzenesulfonamide 6l exhibited the highest dual VEGFR-2/FGFR1 inhibitory activity with IC50 values of 0.025 and 0.026 µM, respectively. It showed a higher activity than sorafenib and staurosporine by 1.8- and 1.3-fold, respectively. Furthermore, compound 6l was further tested on EGFR and PDGFR-β kinases showing IC50 values of 0.106 and 0.077 µM, respectively. The target compounds were tested for their anticancer activity against NCI-60 panel of cancer cell lines at 10 µM concentration, where compound 6l displayed the highest mean growth inhibition percent % (GI%) of 60.38%. Compounds 6a, 6b, 6e, 6f, 6h-l, and 6n-r revealed promising GI% on breast cancer cell lines (MCF-7, T-47D, and MDA-MB-231), and were subjected to IC50 determination on these cell lines. The tested compounds showed a higher activity on T-47D and MCF-7 cell lines over MDA-MB-231 cell line compared to the used reference standard; sorafenib. Compounds 6e, 6h-j, 6l and 6o revealed IC50 values ≤ 20 µM against T-47D cell line, furthermore, they were found to be non-cytotoxic on Vero normal cell line. Furthermore, the effect of the most active compounds 6i, and 6l in T-47D cells on cell cycle analysis progression, cell apoptosis, and apoptosis markers was investigated. Both compounds arrested cell cycle progression at G1 phase, furthermore, they enhanced early and late apoptosis, as well as necrosis. The capability of compounds 6i, and 6l to induce apoptosis was further confirmed by their ability to raise BAX/BCl-2 ratio and caspase-3 level in the treated cells. Cell migration assay revealed that both compounds 6i and 6l have anti-migratory effects compared to control T-47D cells after 24, and 48 h. Molecular docking studies for compounds 6a-r on VEGFR-2 and FGFR1 binding sites showed that they exhibit an analogous binding mode in both target kinases which agrees with that of type II kinase inhibitors.

Exploration of cytotoxicity of iodoquinazoline derivatives as inhibitors of both VEGFR-2 and EGFRT790M: Molecular docking, ADMET, design, and syntheses.

Novel inhibitors of epidermal growth factor receptor (EGFR)T790M/vascular endothelial growth factor receptor-2 (VEGFR-2) were synthesized based on the iodoquinazoline scaffold linked to different heteroaromatic, aromatic, and/or aliphatic moieties. The novel derivatives were in vitro examined for anticancer activities against A549, HCT116, michigan cancer foundation-7 (MCF-7), and HepG2 cells. Molecular modeling was applied to discover their orientation of binding with both VEGFR-2 and EGFR active sites. Compounds 8d, 8c, 6d, and 6c indicated the highest cytotoxicity with IC50 = 6.00, 6.90, 6.12 and 6.24 µM, 7.05, 7.35, 6.80, and 6.80 µM, 5.75, 7.50, 6.90, and 6.95 µM, and 6.55, 7.88, 7.44, and 7.10 µM against the A549, HepG2, HCT116, and MCF-7 cell lines, correspondingly. The cytotoxicity against normal VERO (normal african green monkey kidney cells) of the extremely active eight compounds 6a-d and 8a-d was evaluated. Our compounds exhibited low toxicity concerning normal VERO cells with IC50 = 45.66-51.83 μM. Furthermore, inhibition assays for both the EGFRT790M and VEGFR-2 enzymes were done for all compounds. Remarkable inhibition of EGFRT790M activity was achieved with compounds 6d, 8d, 6c, and 8c at IC50 = 0.35, 0.42, 0.48, and 0.50 µM correspondingly. Moreover, remarkable inhibition of VEGFR-2 activity was achieved with compounds 8d, 8c, 6d, and 6c at IC50 = 0.92, 0.95, 1.00, and 1.20 µM correspondingly. As planned, derivatives 6d, 8d, 6c, and 8c presented exceptional inhibition of both EGFRT790M/VEGFR-2 activities. Finally, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were made for the highly active four compounds 6c, 6d, 8c, and 8d in comparison with erlotinib and sorafenib as reference standards.

Cytotoxicity Screening of Endophytic Fungi from Phaleria macrocarpa (Scheff) Boerl) Collected in Yogyakarta District

Cancer is a disease that is a global problem with a high prevalence and mortality rate. Indonesia has biodiversity with enormous potential as a source of medicinal ingredients. Phaleria macrocarpa (Scheff) Boerl) It is known to contain active metabolites, potentially an anticancer. Some endophytes are reported to be able to produce secondary metabolites similar to their parent plants. This study aimed to obtain endophytic fungi from P. macrocarpa capable of producing compounds with anticancer potential. Endophytes producing anticancer compounds were explored by screening endophytic fungi producing secondary metabolites from parts of the plant P. macrocarpa collected in the Yogyakarta area. The anticancer bioassay (MTT assay) was performed in vitro using cancer cells T47D, MCF7, HeLa, and normal Vero cells. Potential extracts were traced for their mechanism of cell cycle modulation and apoptosis using Flowcytometry. First, fungal identification was carried out on fungi producing potential cytotoxic extracts. Then the compound content was analyzed using LC-HRMS. The results from the six extracts obtained from fruit, leaf, and stem parts showed that the endophytic extract from the leaves (code PC-L2) had the best cytotoxicity compared to other endophytes and showed the best result on MCF-7 cells with an IC50 value of 110.66 µg/mL. The producing PC-L2 extract fungi are closely associated with Clonostachys wenpingii strain DUCC5606. This extract induced apoptosis but not through the mechanism of cell cycle modulation.

Exploring the impact of meso-position fluorination on BODIPYs: Synthesis, electrochemical Insights, and potential therapeutic applications in breast cancer

Three boron dipyrromethane molecules (BODIPYs) were synthesized in this study with different quantities of fluorine in the meso position. The samples were characterized by NMR spectroscopy, absorption, mass spectrometry, and cyclic voltammetry, which was utilized to electrochemically measure the energy gaps between the HOMO (highest-energy occupied molecular orbital) and LUMO (lowest-energy unoccupied molecular orbital). The MTT and SRB assays were used to assess the viability of these dyes in breast cancer cells (MCF-7 and HCC-1806) and African green monkey kidney cells (Vero). The newly synthesized BODIPY tris(perfluorophenoxy)phenyl (1) compound has exhibited remarkable stability and lacks photocytotoxicity in this investigation, thus rendering it a promising candidate for application in bioimaging. At defined concentrations, the BODIPYs bearing perfluorophenyl (2) and hydroxyphenyl (3) moieties have been identified as prospective candidates for photosensitization in photodynamic therapy for breast cancer. Their notable phototoxic properties upon irradiation and the absence of significant metabolic activity reduction in normal VERO cells after 24 h of exposure suggest their potential efficacy in this therapeutic approach.