HeLa Cell Lines Research Articles

Acute toxicity appraisal of Saussurea heteromalla extract and development of its chemotherapeutic herbal dosage form.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

Passifetilactones A-E, Fatty Acid Lactones from the Fruit and Flowers of Passiflora foetida with Cytotoxic Activity.

Phytochemical investigation of the fruit and flowers of Passiflora foetida led to the isolation of 14 compounds, of which five are previously undescribed fatty acid lactones. Four 2-pyrones, passifetilactones A-D (1-4), and one furanone, passifetilactone E (5), were identified by analysis of spectroscopic and spectrometric data. The previously undescribed lactones were tested for cytotoxic activities against the cancer cell lines HeLa, A549, PC-3, KKU-055, and KKU-213A and two normal cell lines, Vero and MMNK-1. Passifetilactones B (2) and C (3) displayed good to mild cytotoxic activity, at IC50 3.7-25.9 μM and 12.2-19.8 μM, respectively, against six cell lines, but were weakly active against the MMNK-1 cell line. Passifetilactones B and C (2 and 3) showed cell apoptosis induction on the KKU-055 cell line in a flow cytometry experiment. Passifetilactone D (4) is an isolation artifact produced by purification over silica gel, but we demonstrated that it can also be slowly formed within the crude EtOAc extract. This is the first investigation of the flowers and the fruit of this plant.

A New Rare Halogenated Depside from Lichen and Study of its Anti-Proliferative Activity.

Lichens are a symbiotic association of algae and fungus, belonging to the family Parmeliaceae. Some lichen species are edible and used as an active ingredient for preparation of exotic spices as well as folklore medicine to cure different kinds of ailments. A specimen of lichen was collected from Munner in the Kerala State of South India for chemical profiling. Chemical analyses of the diethyl ether extract of the defatted lichen led to the isolation of six phenols 1-6 with variation of relative abundance. Amongst them, the relative abundance of compound 3 was the greatest (1 % of crude extract) and it was identified as atranorin. The structures of known compounds were confirmed by comparison of their 1H-NMR, 13C NMR, and mass data with published values available in the literature. In vitro bioassay for anti-proliferative activity of these compounds has been conducted against various human cancer cell lines in comparison with paclitaxel as control using SRB assay. Interestingly, a new compound 5 was found along with previously reported compounds from this lichen. This new compound was designated as fluoroatranorin 5 which was reported for the first time herein. The structural characterization of a new depside was determined by spectral methods such as 1H-NMR, 13C NMR, 19F NMR, IR, LC-HRESI-MS, and LC-MS/MS study. Its structure was confirmed by single crystal X-ray diffraction study. This new compound was designated as fluoroatranorin 5 which was reported first time herein. Anti-proliferative activity of all these compounds was evaluated against six different cancer cell lines. The inhibitory activity, IC50 value of compounds 1-3 and 5 exhibited at 99.64, 102.04, 109.20, 53.0 and 2.4 μM on cancer cell lines HT-29 (colon), Hela (cervical), HT-29, HPAC (pancreas) and A2780 (ovarian cancer cell line) respectively in comparison with paclitaxel as control. The new compound 5 exhibited significant activity with IC50 value 2.4 μM on A2780 ovarian cancer cell line.

Chitosan-based pH-sensitive semi-interpenetrating network nanoparticles as a sustained release matrix for anticancer drug delivery

Chitosan-based nanoparticles have demonstrated a growing potential for use in the drug delivery systems due to their remarkable versatility. To enhance the effectiveness of chitosan-based nanoparticles for stimulus-responsive anticancer drug delivery, a novel pH-sensitive semi-interpenetrating networks (semi-IPN) of chitosan-poly(1-vinyl imidazole) (CS-PVIm) and Chitosan-poly(methacrylic-acid) (CS-PMAA) nanoparticles were synthesized through free radical polymerization. The semi-IPN nanoparticles were analyzed to evaluate their suitability as drug carrier. The SEM analysis revealed that the nanoparticles were spherical and within the nanoscale size range. The average particle size measured by DLS for CS-PMAA nanoparticles was 107.9 nm without the drug and 175.2 nm after the drug encapsulation. CS-PVIm-nanoparticles had an average size of 138.32 nm, which was increased to 165.84 nm after the drug loading. ATR-FTIR confirmed the formation of CS-PVIm and CS-PMAA nanoparticles. Cytotoxicity analysis showed that the nanoparticles are biocompatible, with over 95 % of cell survival for the HeLa cell lines. Further, Doxorubicin-hydrochloride (Dox) loaded nanoparticles exhibited sustained drug release caused by the protonation and deprotonation of their functional groups based on pH change. The CS-PVIm-nanoparticles showed encapsulation efficiency (EE) of 57 %, whereas EE of CS-PMAA-nanoparticles were 52 %, respectively. This research presents a straightforward method for producing intelligent pH-responsive semi-IPN-nanoparticles tailored for anticancer drug delivery.

Antiproliferative and antimicrobial compounds from Streptomyces levis: supported by in vitro and in silico molecular docking approach

The present work describes the investigation of secondary metabolites produced by rhizospheric soil isolate Streptomyces levis with respect to partial purification, bioactivity, structural elucidation, and docking study. MIC (Minimum Inhibitory Concentration) of the fraction was found to be 16 µg/mL, 32 µg/mL, and 8 µg/mL against S. aureus, E. coli, and C. albicans respectively. The fraction exhibited an IC50 of 90.48 μg/mL and 59.10 µg/mL against L929 and HeLa cell lines respectively. Spectroscopic analysis showed abundant of Isofucosterol 3-O-[6-O-(9-Octadecanoyl)-b-D-glucopyranoside], and Viniferal. These compounds were docked against receptor molecules E6, E7, Caspase-3, and Bcl2. The in-silico results suggested that all the secondary metabolites showed higher docking scores than the standard compound 5-Fluorouracil. Molecular docking study and published literature suggested that Isofucosterol 3-O-[6-O-(9-Octadecanoyl)-b-D-glucopyranoside] inactivated viral oncoprotein E7 and arrested the cell cycle from entering in S phase. Viniferal induced apoptosis by inactivation of Bcl2.

Optimizing enhanced heavy metal detoxification by novel hybrid fungal hyphae-nano-biocomposite functionalized with graphene oxide: Unravelling process parameters & adsorption modelling

Heavy metal pollution poses significant environmental and health risks, demanding efficient novel remediation strategies. This paper presents a fungal hyphae-based nano-biocomposite integrated with graphene oxide (FHGO) for the efficient removal of heavy metals from aqueous solutions. The successful formation of nanoparticles was investigated by morphological characterization using Fourier Transform Infrared Spectroscopy (FTIR), Scanning electron microscopy (SEM) & X-ray diffraction (XRD). Through comprehensive exploration of process parameters, including pH, initial concentration, and contact time, the nano-biocomposite demonstrated exceptional removal efficiencies exceeding 90% for both heavy metals i.e. chromium (Cr6+) & nickel (Ni2+). The optimum pH conditions for Cr (VI) removal was 4,whereas it was 9 for Ni (II) removal. The equilibrium data were well-fitted to Langmuir isotherm models, suggesting monolayer adsorption onto a homogeneous surface with adsorption capacities of 38.89 mg/g & 42.88 mg/g for Ni (II) & Cr (VI), respectively, with value of R2=0.997. Additionally, biocompatibility assessments via (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) MTT assays on Henrietta Lacks (HeLa) cell line cultures revealed a low IC50 value of FHGO nano-biocomposite, affirming the efficiency of the composite for biomedical applications. Furthermore, seed germination assays indicated comparatively minimal hindrance to plant growth in the treated sample, highlighting the composite's potential for environmental remediation without compromising plant health. These findings underscore the promising potential of the fungal hyphae-based nano-biocomposite with GO as an effective and environmentally safe adsorbent for heavy metal removal, with implications for sustainable environmental management and public health protection.

Triterpenoids with α-glucosidase inhibitory and cytotoxic activities from the fruits of Schisandra chinensis

An intensive phytochemical investigation into the fruits of Schisandra chinensis afforded 28 triterpenoids incorporating diverse backbones with methyl-migration, ring-expansion and ring-opening features. Among them, ten compounds (1−10) including three likely extracting artefacts (8−10) were described for the first time. Their structures were fully characterized by comprehensive spectroscopic analyses, with the absolute configurations established via electronic circular dichroism and Mosher’s NMR techniques. Preliminary biological evaluations revealed that nine isolates showed inhibitory activity against the hyperglycemic target α-glycosidase and 12 compounds exerted cytotoxicity toward three female tumor cell lines (Hela (cervical), MDA-MB231 and MCF-7 (breast)). Compound 6 exhibited the most promising potency on all the three tested cancer cells, and further assessment demonstrated that it could induce significant cell apoptosis and cycle arrest, as well as suppress cell migration, by regulating relevant proteins in MDA-MB231 cells.

Nm-Nano: a machine learning framework for transcriptome-wide single-molecule mapping of 2´-O-methylation (Nm) sites in nanopore direct RNA sequencing datasets

ABSTRACT 2´-O-methylation (Nm) is one of the most abundant modifications found in both mRNAs and noncoding RNAs. It contributes to many biological processes, such as the normal functioning of tRNA, the protection of mRNA against degradation by the decapping and exoribonuclease (DXO) protein, and the biogenesis and specificity of rRNA. Recent advancements in single-molecule sequencing techniques for long read RNA sequencing data offered by Oxford Nanopore technologies have enabled the direct detection of RNA modifications from sequencing data. In this study, we propose a bio-computational framework, Nm-Nano, for predicting the presence of Nm sites in direct RNA sequencing data generated from two human cell lines. The Nm-Nano framework integrates two supervised machine learning (ML) models for predicting Nm sites: Extreme Gradient Boosting (XGBoost) and Random Forest (RF) with K-mer embedding. Evaluation on benchmark datasets from direct RNA sequecing of HeLa and HEK293 cell lines, demonstrates high accuracy (99% with XGBoost and 92% with RF) in identifying Nm sites. Deploying Nm-Nano on HeLa and HEK293 cell lines reveals genes that are frequently modified with Nm. In HeLa cell lines, 125 genes are identified as frequently Nm-modified, showing enrichment in 30 ontologies related to immune response and cellular processes. In HEK293 cell lines, 61 genes are identified as frequently Nm-modified, with enrichment in processes like glycolysis and protein localization. These findings underscore the diverse regulatory roles of Nm modifications in metabolic pathways, protein degradation, and cellular processes. The source code of Nm-Nano can be freely accessed at https://github.com/Janga-Lab/Nm-Nano.

A sustainable green-approach for biofabrication of chitosan nanoparticles, optimization, characterization, its antifungal activity against phytopathogenic Fusarium culmorum and antitumor activity.

Chitosan is a natural non-toxic, biocompatible, biodegradable, and mucoadhesive polymer. It also has a broad spectrum of applications such as agriculture, medical fields, cosmetics and food industries. In this investigation, chitosan nanoparticles were produced by an aqueous extract of Cympopogon citratus leaves as a reducing agent. According to the SEM and TEM micrographs, CNPs had a spherical shape, and size ranging from 8.08 to 12.01 nm. CNPs have a positively charged surface with a Zeta potential of + 26mV. The crystalline feature of CNPs is determined by X-ray diffraction. There are many functional groups, including C꞊C, CH2-OH, C-O, C-S, N-H, CN, CH and OH were detected by FTIR analysis. As shown by the thermogravimetric study, CNPs have a high thermal stability. For the optimization of the green synthesis of CNPs, a Face centered central composite design (FCCCD) with 30 trials was used. The maximum yield of CNPs (13.99 mg CNPs/mL) was produced with chitosan concentration 1.5%, pH 4.5 at 40°C, and incubation period of 30 min. The antifungal activity of CNPs was evaluated against phytopathogenic fungus; Fusarium culmorum. A 100% rate of mycelial growth inhibition was gained by the application of 20mg CNPs/mL. The antitumor activity of the green synthesized CNPs was examined using 6 different cell lines, the viability of the cells reduced when the concentration of green synthesized CNPs increased, the IC50 dose of the green synthesized CNPs on the examined cell lines HePG-2, MCF-7, HCT-116, PC-3, Hela and WI-38 was 36.25 ± 2.3, 31.21 ± 2.2, 67.45 ± 3.5, 56.30 ± 3.3, 44.62 ± 2.6 and 74.90 ± 3.8; respectively.

Synthesis and characterization of silver nanoparticle conjugated-chalcones and their evaluation for antimalarial, cytotoxicity and haemolytic potential at in vitro level

Silver nanoparticles (AgNPs) have shown a wide range of antimicrobial activities over the last 2 decades, but little is known about their antimalarial activity. Therefore, in the present study, AgNPs were surface functionalized by chalcones to create an efficient bioactive molecular surface that can enhance the antimalarial competency of both chalcones as well as chemically synthesized AgNPs. The AgNPs-conjugated chalcones have been synthesized using a chemical method employing the EDC-NHS coupling method. The characterization of AgNPs and AgNPs-conjugated chalcones was done through various analytical techniques. The SYBR Green I assay was performed for in vitro antimalarial activity, and cell cytotoxicity was done on HeLa cell line with MTT assay to calculate the IC50 and CC50, respectively. Haemolytic effect on fresh RBCs of these nanoconjugates were observed for 3 h and 24 h. AgNPs and AgNPs-conjugated chalcones have spectra at 420 nm and between 350 and 375 nm, respectively. The IC50 values of all the three conjugates for antimalarial activity ranged from 0.30 to 0.80 μg/mL. The present study provides a new method of synthesizing AgNPs-conjugated chalcones. Also, these synthesized conjugates show better antimalarial potential and reduced cellular toxicity compared to bared chalcones under an in vitro culture system. However, a further pre-clinical study on the murine model of malaria along with toxicity parameters is needed to provide more clarity.Graphical abstract

Dissimilar effect of organometallic ruthenium complexes on the viability of MDR and non-MDR experimental models

Ruthenium complexes containing triphenylphosphine diamide ligands were prepared, characterized, and tested for their biological activity against various cancer cell lines and the malaria parasite, Plasmodium falciparum. The effect of M (mono-substituted) and B (bis-substituted) complexes on the human cervical carcinoma (HeLa) cell line was investigated using the MTT assay. Five (B2, B3, B5, B6, and B13) of the 24 synthesized ruthenium complexes showed significant effects with IC50 values ranging between 0.3 and 2.3 μM. Evaluation of the potential biomolecular targets of B2 and B13 by fluorescence spectroscopy revealed relevant interactions with BSA and only a weak affinity for ctDNA. Complexes M2, B2, M13 and B13 were selected for further biological characterization. Their effect on the viability of two ovarian cancer cell lines was compared to normal cell lines, denoting their selectivity. Upon treatment of four different drug-resistant gynaecological cancer cell lines, differing in their multidrug-resistant phenotypes, the efficacy of the bis-substituted complexes was shown to be greater than their mono-substituted counterparts. The non-MDR cells are sensitive to all the tested complexes, compared to MDR cells which are less sensitive. Upon investigation of complexes M2, M13, B2, and B13 against sensitive and multidrug-resistant parasite strains of P. falciparum, the bis-substituted complexes were again shown to be the most potent, with submicromolar activity against both strains. Furthermore, the resistance indexes for the complexes were approximately equal to 1, which is at least 5-fold lower than chloroquine diphosphate, suggesting the ability of these complexes to retain their activity in resistant forms of the parasite.

Isolation and structure determination of a new bisabolane-type sesquiterpenoid with cytotoxicity from Penicillium oxalicum MZY-202312-521

Endophytic fungi can produce attractive secondary metabolites with various biological activities that have contributed significantly to pharmacotherapy. In this study, three bisabolane-type sesquiterpenoids, including a new one, namely, inonotic acid C (1), together with previously reported compounds (S)-(+)-11-dehydrosydonic acid (2) and sydonic acid (3), were isolated from a marine algal-derived endophytic fungus Penicillium oxalicum MZY-202312-521. Their structures were determined by means of extensive spectroscopic analyses. The absolute configurations of inonotic acid C (1) were established by single-crystal X-ray diffraction method. In vitro cytotoxic experiments on human A549, MCF-7, HeLa, and HepG2 carcinoma cell lines were carried out. The new compound inonotic acid C (1) was found to possess strong inhibitory activity against the MCF-7 cell line, with an IC50 value of 7.7 μM.

Folic acid-mediated enhancement of the diagnostic potential of luminescent europium-doped hydroxyapatite nanocrystals for cancer biomaging

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.

Macrophorins H and L, two new HMG-conjugate macrophorins from rihzospheric Penicillium sp. NX-05-G-3

Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM.

CircCUL3 drives malignant progression of cervical cancer by activating autophagy through sponge miR-223-3p upregulation of ATG7

Circular RNA (circRNA) has emerged as a pivotal regulatory factor in cancer biology, yet its exact role in cervical cancer remains incompletely understood. In this study, we investigated the functional role of circCUL3 in cervical cancer and explored its potential as a therapeutic target. Functional gain and loss experiments were conducted in Hela and Siha cell lines to elucidate the biological functions of circCUL3 in cervical cancer. The results revealed that circCUL3 overexpression significantly enhanced cell viability, migration, and invasion while suppressing apoptosis, while circCUL3 knockout displayed the opposite effects. Mechanistically, we identified hsa-miR-223-3p as a target of circCUL3, with its expression being negatively regulated by circCUL3. Furthermore, we discovered that circCUL3 could sequester miR-223-3p, leading to the upregulation of ATG7 expression, and this was linked to the regulation of autophagy in cervical cancer cells. In vivo validation using a xenograft mouse model further supported our in vitro findings. Notably, we found that chloroquine (CQ), an autophagy inhibitor, restored miR-223-3p expression and counteracted the oncogenic effect of circCUL3 overexpression. In conclusion, circCUL3 potentially contributes to the malignant progression of cervical cancer by acting as a sponge for miR-223-3p, resulting in the upregulation of ATG7 and the activation of autophagy.

Antioxidant and Anticancer Potential of Extracellular Polysaccharide from Porphyridium aerugineum (Rhodophyta)

Porphyridium aerugineum is a unicellular freshwater red microalga that synthesizes and secretes into the culture medium an extracellular polysaccharide (EPS). In this study, algal growth and polysaccharide production, as well as the antioxidant capacity and antitumor effect of Porphyridium aerugineum EPS (PaEPS), were investigated. Cultivation of the microalgae was carried out in a photobioreactor under controlled conditions. Algal growth and the amount of EPS were monitored daily. The accumulated polysaccharide was extracted and lyophilized. At the end of cultivation, the concentration of microalgal biomass and PaEPS reached 3.3 and 1.2 g L−1, respectively. To examine the antioxidant capacity of PaEPS, FRAP and ABTS assays were performed. The cytotoxic activity of PaEPS was evaluated on the tumor cell lines MCF-7 (breast cancer) and HeLa (cervical adenocarcinoma) and on BJ (a non-tumor human skin fibroblast cell line), using MTT assay. The results obtained indicated that P. aerugineum polysaccharide exhibited a high ABTS radical-scavenging activity reaching up to 55%. The cytotoxic effect was best expressed in MCF-7 cells treated for 72 h with 1000 µg/mL PaEPS, where tumor cell proliferation was inhibited by more than 70%. Importantly, the PaEPS treatments did not significantly affect the viability of BJ cells. These findings promote the biotechnological production of P. aerugineum extracellular polysaccharide and reveal its potential as an anticancer and antioxidant agent for future applications.

In vitro antioxidant and anticancer potential of intra-cellular ethyl acetate extract of marine-derived fungus Talaromyces tratensis SS10

Marine fungi are well-known for producing structurally distinct secondary metabolites, making them potential sources of novel therapies. The present investigation aims to study the in vitro antioxidant and anticancer potential of intra-cellular crude ethyl acetate extracts of Talaromyces tratensis SS10. In the present study, qualitative and quantitative phytochemical studies of various solvent extracts of T. tratensis have been carried out using standard protocols. Later, ethyl acetate extract of T. tratensis was analyzed for phytochemicals using Gas Chromatography Mass Spectrometry (GC-MS). Further, the antioxidant properties of the T. tratensis ethyl acetate extract have been done by Ferric reducing antioxidant power assay (FRAP). Further, the anticancer potential of this extract has been carried out by MTT assay against human cancer cells such as MDA MB 231, HeLa, and HT-29. Ethyl acetate exhibited a higher yield of chemical extraction than the other solvents used. The GCMS analysis of T. tratensis ethyl acetate extract revealed major phytoconstituents such as N-(1,1-Dimethylpropyl)-2,2,3-trimethylaziridine-1-carboxamide, 1-Undecanol, 5,5 Dimethyl-3-vinyl cyclohex-2-en-1-one, 1,2-Benzenedicarboxylic acid, bis (2-methyl propyl) ester. T. tratensis ethyl acetate extract showed the highest percentage of Fe3+ reduction (48.093±1.469%) at 120 μg/mL, with an IC50 value of 157.26 μg/mL concentration. Furthermore, 100 μg/mL of the extract showed significant cell death rates in cytotoxic assays, indicating a low percentage of viable cells for all three examined cell lines. The T. tratensis ethyl acetate extract has shown a dose-dependent cytotoxic effect against all tested cancer cell lines. The better IC50 value (6.25 μg/mL) was recorded in the case of HeLa cell lines followed by 12.5 μg/mL for both MDA MB 231 and HT-29 cell lines. The presence of bioactive compounds such as Benzeneethanamine, N-[(pentafluorophenyl)methylene]-beta.,3,4-tris[(trimethylsilyl) oxy]-, 1,2-Benzenedicarboxylic acid, bis(2-methylpropyl) ester, and cyclononasiloxane, octadecamethyl- may have contributed to the ethyl acetate extracts’ strong antioxidant and anticancer properties. The current study’s findings show that T. tratensis SS10 has the potential for drug development due to its chemical constituents, which possess various biological activities.

Cytocompatible hydrogel derived from dextrin and Poly(N-Vinyl acetamide) toward controlled antimicrobial release

The work aims to develop a biopolymer-dextrin-based three-dimensional crosslinked hydrophilic material for antimicrobial delivery. The copolymer (Dxt-PNVA) has been prepared by in-situ grafting of poly(N-vinylacetamide), followed by cross-linking with N,N'-methylenebisacrylamide with dextrin. By varying the concentrations of the reactants, an optimized copolymer (Dxt-PNVA 5) with the lowest % of crosslinking has been chosen for biomedical applications. The copolymeric gel has been characterized in detail using various techniques, followed by its cytocompatibility study using HeLa Cell lines that confirm the cytocompatible nature of the material. Copolymeric gel is a suitable material for the effective release of two antimicrobials (amoxicillin trihydrate and ornidazole) from tablet formulation for a prolonged period of 24 h. The obtained data demonstrates that the cytocompatible hydrogel has the potential characteristics of a daily dose administration for amoxicillin trihydrate and ornidazole.

Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents.

To discover new Werner (WRN) helicase inhibitors, a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives were designed and synthesized through a structural optimization strategy, and the anticancer activities of 25 new target compounds against PC3, K562, and HeLa cell lines were evaluated by the MTT assay. Some of these compounds exhibited excellent inhibitory activity against three different cancer cell lines. Compounds 6a, 8i, and 13a showed better antiproliferative activity against K562 cells, with IC50 values of 3871.5, 613.6 and 134.7nM, respectively, than did paclitaxel (35.6nM), doxorubicin (2689.0nM), and NSC 617145 (20.3nM). To further verify whether the antiproliferative activity of these compounds is dependent on WRN, PC3 cells overexpressing WRN (PC3-WRN) were constructed to further study their antiproliferative potency in vitro, and the inhibition ratio and IC20 values showed that compounds 6a, 8i, and 13a were more sensitive to PC3-WRN than were the control group cells (PC3-NC). The IC20 ratios of compounds 6a, 8i, and 13a to PC3-NC and PC3-WRN were 94.3, 153.4 and 505.5, respectively. According to the docking results, the compounds 6a, 8i, and 13a overlapped well with the binding pocket of 6YHR. Further study demonstrated that among the tested compounds, 13a was the most sensitive to PC3-WRN. In summary, our research identified a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential WRN-dependent anticancer agents.

Design, Synthesis and Biological Evaluation of Novel Gypsogenin Derivatives as Potential Anticancer and Antimicrobial Agents.

Natural compounds are important sources for the treatment of chronic disorders such as cancer and microbial infectious disorders. In this research, Gypsogenin and its derivatives (2 a-2 f) have been tested against different cancer cell lines (MCF-7, HeLa, Jurkat and K562 cell lines) and further analyzed for cell proliferation, cell death type, and for act of the mechanism. Cell proliferation was determined by the MTT method and cell death types were analyzed with HO/PI staining. Fibroblast Growth Factor 1 (FGF-1), Interleukin 1 (IL-1), Interleukin 6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-α), key players in breast cancer development and progression, were determined by Elisa kits. Results showed that compound 2 e inhibited the MCF-7 cell line proliferation with an IC50 value of 0.66±0.17 μM with 93.38 % apoptosis rate. Compound 2 e also decreased FGF-1, IL-1, IL-6, and TNF-α levels. Molecular docking studies performed in the binding site of FGFR-1 indicated that compound 2 e formed key hydrogen bonding with Arg627 and Asn568. Besides, compounds 2 a-2 f were evaluated for their antimicrobial activities against gram-negative and gram-positive bacteria and C. albicans via the microdilution method. Overall, compound 2 e stands out as a potential anticancer agent for future studies.