Cytotoxicity Studies Research Articles

Design of Highly Porous Materials Based on Chitosan/Pectin Interpolyelectrolyte Complex for Wound Healing Application

Interpolyelectrolyte complexes (IPECs) of polysaccharides are multifunctional polymer materials that improve the mechanical and physicochemical properties of individual polysaccharides. In this study, highly porous (>90%) materials based on IPECs of versatile natural polysaccharides, chitosan (30 and 1,200 kDa) and pectin, are obtained by freeze-drying technique. To enhance the interaction between chitosan and pectin macromolecules, the latter are chemically functionalized with dialdehyde groups. The chitosan-/aldehyde-functionalized pectin (Chit/AF-Pect) polyelectrolyte complex sponges obtained are characterized using SEM, FTIR spectroscopy, and TGA. The swelling capacity study reveals a higher swelling ratio of IPEC sponges with an increase in both the molecular weight and content of chitosan: for Chit30/AF-Pect, the swelling ratio rises from 327% to 480%, while for Chit1200/AF-Pect, from 681% to 1,066%. Additionally, the in vitro degradation test demonstrates higher stability of Chit1200/AF-Pect sponges in comparison with those of Chit30/AF-Pect: after 4 days of incubation, the weight losses are found to be 9%–16% and 18%–41%, respectively. The cytotoxicity study shows that Chit30/AF-Pect sponges are noncytotoxic, with cell viability values >70%. Furthermore, the Chit30/AF-Pect sponges, obtained at chitosan:pectin weight ratio of 5:1, exhibit bactericidal activity against Escherichia coli BIM B-984 G, Pseudomonas aeruginosa BIM B-807 G, Staphylococcus aureus BIM B-1841, and slightly inhibit the growth of Enterococcus faecalis BIM B-1530 G. These findings indicate that the obtained Chit30/AF-Pect sponges can be used to create wound dressings for wound healing applications.

Enhanced localized therapeutic precision: A face-to-face folate-targeted Cu2+-mediated nanotherapy with thermosensitive sustained-release system

Safe and effective Cu2+ supplementation in local lesion is crucial for minimizing toxicity of DSF-based chemotherapy. Targeted delivery of Cu2+ appears more promising. Intraperitoneal chemotherapy for peritoneal carcinoma (PC) establishes “face-to-face” contact between targeted nanocarriers and tumor tissue. Herein, this study developed a biodegradable, injectable thermosensitive hydrogel that coencapsulating DSF submicroemulsion (DSF-SE) and folate-modified liposome loading glycyrrhizic acid-Cu (FCDL). FCDL acted as ‘beneficial horse’ to target the tumor-localized folate receptor, thus liberating Cu2+ in tumor nidus. The prepared FCDL and DSF-SE were found with uniform sizes (160.2 nm, 175.4 nm), low surface charge (−25.77 mV, −16.40 mV) and high encapsulation efficiency (97.93 %, 90.08 %). In vitro drug release profile of FCDL, DSF-SE and FCDL＆DSF-SE@G followed a sustained release pattern. And the release behavior of Cu2+ from FCDL was pH-related, i.e., Cu2+ was released faster under acidic condition. When FCDL and DSF-SE were loaded into an PLGA-PEG-PLGA-based hydrogel system, FCDL＆DSF-SE@G was formed to ensure separated delivery of Cu2+ and DSF in space but synchronized release over time. The rheology experiment showed a satisfactory gelling temperature of 32.7 °C. In vitro cytotoxicity study demonstrated that FCDL＆DSF-SE@G significantly lowered the IC50 of free Cu2+/DSF, Cu2+/DSF hydrogel and non-targeted analogue by almost 70 %, 65 % and 32 %, respectively. Accordingly, in tumor-bearing mice, FCDL＆DSF-SE@G augmented the tumor inhibition rates for the same formulations by 352 %, 145 % and 44 %, respectively. The main mechanism was attributed to higher uptake of FCDL and DSF-SE, resulting in increased Cu(DDTC)2 formation, ROS production and cell apoptosis. In conclusion, this targeted nanotherapy approach with dual-nanocarriers loaded hydrogel system, with its focus on face-to-face contact between nanocarriers and tumor tissues in the peritoneal cavity, holds significant promise for intraperitoneal chemotherapy in PC.

Synthesis and drug release kinetics of ciprofloxacin from polyacrylamide/dextran/carbon quantum dots (PAM/Dex/CQD) hydrogels

Sustainable release of drug by utilizing β-cyclodextrin (β-CD) based inclusion complex (IC) is the prime objective of the present work. Herein, polyacrylamide/dextran containing carbon quantum dots (PAM/Dex/CQD) nanocomposite hydrogels are prepared by in situ polymerization of acrylamide. The incorporation of CQD triggers the change in orientation of the PAM/Dex polymeric chains to result the formation of stacked surface morphology of the hydrogel. The average particle size of CQD is found to be 4.13 nm from HRTEM analysis. As-synthesized nanocomposite hydrogel exhibits an optimum swelling ratio of 863 % in aqueous medium. The cytotoxicity study is conducted on HeLa cells by taking up to 2 μM concentration of the prepared nanocomposite hydrogel demonstrate 78 % cell viability. In present study, ciprofloxacin (Cipro) is taken as model drug that achieves release of 64.15 % in 32 h from β-Cipro@PAM/Dex/CQD hydrogels in acidic medium. From theoretical study, release rate constants, R2, Akaike information criterion (AIC) and model selection criterion (MSC) are computed to determine the best fitted kinetics model. Peppas-Sahlin model is the best fitted kinetics model for β-Cipro@PAM/Dex/CQD and concluded that the release of Cipro follows Fickian drug diffusion mechanism in acidic medium.

Hepatic toxicity induced by dietary treatment of rats with hexaconazole: insights from a cytotoxic and genotoxic study

ABSTRACT Hexaconazole (HEX), a widely used triazole fungicide in agriculture, was investigated for its hepatotoxic effects on albino Wistar rats. Compared to the control rats, the treated rats showed a significant increase in absolute and relative liver weight over both 3 months (p < 0.05) and 6 months (p < 0.001). Oxidative biomarkers indicated a notable rise in malondialdehyde (MDA) by 137% (p < 0.001), increased reduced glutathione (GSH) by 32% (p < 0.01), and significant reductions in antioxidant enzymes, including a 63% decrease in catalase (CAT, p < 0.001) and a 15% decrease in superoxide dismutase (SOD, p < 0.01). Glutathione-S-transferase (GST) levels also decreased significantly after 3 and 6 months (p < 0.05). The micronucleus test in liver cells indicated an elevation in the appearance of micronuclei in rats treated with HEX for 6 months (p < 0.01). This study demonstrates, for the first time, that HEX can induce genotoxicity in the liver.

Enhancing Curcumin’s therapeutic potential in cancer treatment through ultrasound mediated liposomal delivery

Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin’s anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm2 power density with 0.6 × 107 microbubbles/mL. Furthermore, the study delved into curcumin liposomes’ cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.

DESIGN, DEVELOPMENT AND IMPROVEMENT OF AN EMULGEL CONTAINING SILVER NANOPARTICLES AND VITAMIN D-3 FOR ITS POTENTIAL TO ACCELERATE THE HEALING OF WOUND

Objective: The aim of this research work was to prepare a topical emulgel based dosage form incorporated with vitamin D-3 and silver nanoparticles to reduce the wound healing time in any kind of wound. Methods: Central Composite Design (CCD) was applied for the optimization of emulgel by using Design expert software. Three responses (pH, viscosity, and in vitro drug release) and two factors (Carbopol concentration and stirring duration) were chosen, and Statistical Analysis of Variance (ANOVA) revealed that all the factors were significantly affecting the responses. Silver Nanoparticles (SNPs) was prepared with Green Tea Extract (GTE) and evaluated for particle size, Poly Dispersity Index (PDI), zeta potential and Fourier Transform Infra-red (FTIR) spectroscopy and revealed that SNPs of desired range and stability have been synthesized. Here excision wound model was used to evaluate the wound healing activity of formulation in vivo. Results: Maximum in vitro release 88.2±2.1 has shown by the optimized formulation F13, pH and viscosity were also found in optimum range i.e., 6.2±0.4 and 1672±33 respectively, followed by Korsmeyer and Peppas model. Total eight groups were designed for animal study and silver sulphadiazine was used as marketed formulation. F13 formulation was further evaluated for in vivo data, it was revealed that emulgel loaded with high dose of vitamin D-3 along with silver nanoparticles has shown 100.5±1.7% wound contraction, while marketed formulation has shown 103.7±1.1% wound contraction, which was much similar with test formulation. Cytotoxic cell study was done using assay on chicken egg, formulation has not shown any cytotoxic behaviour like haemolysis and cell damage on chick embryo’s blood vessels. Accelerated stability study of the optimized formulation was also performed to check whether the formulation was stable or not and it was revealed that optimized formulation was found stable for the period of six months. Conclusion: It was revealed that emulgel loaded with high dose of vitamin D-3 and SNPs found suitable to accelerate wound healing and showed almost similar response in wound contraction on comparison with marketed formulation. This emulgel promised to controlled the delivery of the drug for the longer duration.

Receptor Targeting Using Copolymer-Modified Gold Nanoparticles for pCMV-Luc Gene Delivery to Liver Cancer Cells In Vitro.

The formulation of novel delivery protocols for the targeted delivery of genes into hepatocytes by receptor mediation is important for the treatment of liver-specific disorders, including cancer. Non-viral delivery methods have been extensively studied for gene therapy. Gold nanoparticles (AuNPs) have gained attention in nanomedicine due to their biocompatibility. In this study, AuNPs were synthesized and coated with polymers: chitosan (CS), and polyethylene glycol (PEG). The targeting moiety, lactobionic acid (LA), was added for hepatocyte-specific delivery. Physicochemical characterization revealed that all nano-formulations were spherical and monodispersed, with hydrodynamic sizes between 70 and 250 nm. Nanocomplexes with pCMV-Luc DNA (pDNA) confirmed that the NPs could bind, compact, and protect the pDNA from nuclease degradation. Cytotoxicity studies revealed that the AuNPs were well tolerated (cell viabilities > 70%) in human hepatocellular carcinoma (HepG2), embryonic kidney (HEK293), and colorectal adenocarcinoma (Caco-2) cells, with enhanced transgene activity in all cells. The inclusion of LA in the NP formulation was notable in the HepG2 cells, which overexpress the asialoglycoprotein receptor on their cell surface. A five-fold increase in luciferase gene expression was evident for the LA-targeted AuNPs compared to the non-targeted AuNPs. These AuNPs have shown potential as safe and suitable targeted delivery vehicles for liver-directed gene therapy.

Engineered microbubbles decorated with red emitting carbon nanoparticles for efficient delivery and imaging

Altering the route of uptake by the cells is an attractive strategy to overcome drug-receptor adaptation problems. Carbon nanoparticles (CNPs) with emission beyond tissue autofluorescence for imaging biological tissues were used to study the phenomenon of uptake by the cells. In this regard, red-emitting carbon nanoparticles (CNPs) were synthesized and incorporated onto lipid microbubbles (MBs). The CNPs showed red emissions in the range of 640 nm upon excitation with 480 nm wavelength of light. Atomic force microscopic and confocal microscopic images showed the successful loading of CNPs onto the MB. Carbon nanoparticle loaded microbubbles (CNP-MBs) were treated with NIH 3 T3 cells at different concentrations. Confocal microscopic imaging studies confirm the presence of CNPs inside the treated cells. Cytotoxicity studies revealed that the CNPs showed minimal toxicity towards cells after loading onto MBs. The CNPs are usually taken up by the cells through the clathrin-mediated (CME) pathway, but when loaded onto MBs, the mechanism of uptake of CNPs is altered, and the uptake by the cells was observed even in the presence of inhibitors for the CME pathway. Loading CNPs onto MBs resulted in the uptake of CNPs by the cell through micropinocytosis and sonophoresis in the presence of ultrasound. The in vivo uptake CNP-MBs were performed in Danio rerio (Zebrafish larvae). This study provides insights into altering the uptake pathway through reformulation by loading nanoparticles onto MBs.

Synthesis, characterization, cytotoxicity study, interaction with DNA and topoisomerase IIα of square-planar complexes with thiosemicarbazones

In this study, we report the synthesis and characterization of eight new palladium complexes and a nickel complex containing thiosemicarbazone ligands derived from chalcones and benzalketones. The techniques of Infrared and UV–visible spectroscopy, Nuclear Magnetic Resonance, Mass Spectrometry, and Elemental Analysis fully characterized the compounds. Crystallography was successful for five complexes and two ligands, allowing for X-ray Diffraction analysis. Molecular docking studies and assays involving DNA interaction via agarose gel electrophoresis and UV–Vis titration revealed no DNA interaction or inhibition of topoisomerase IIα enzyme activity. However, these compounds demonstrated potent cytotoxic effects (IC50) against breast tumor (MCF-7) and prostate (DU-145) cell lines, as well as non-tumor prostate (PNT2) cell lines. These findings highlight the relevance of structural variations and the metallic center's nature in achieving cytotoxic effects, offering insights into the development of bioactive compounds.

Oxidovanadium(V) Schiff Base Complexes Derived from Chiral 3-amino-1,2-propanediol Enantiomers: Synthesis, Spectroscopic Studies, Catalytic and Biological Activity.

Oxidovanadium(V) complexes, [(+)VOL1-5] and [(-)VOL1-5], with chiral tetradentate Schiff bases, which are products of monocondensation of S(‒)-3-amino-1,2-propanediol or R(+)-3-amino-1,2-propanediol with salicylaldehyde derivatives, have been synthesized. Different spectroscopic methods, viz. 1H and 51V NMR, IR, UV-Vis, and circular dichroism, as well as elemental analysis, have been used for their detailed characterization. Furthermore, the epoxidation of styrene, cyclohexene, and two monoterpenes, S(‒)-limonene and (‒)-α-pinene, using two oxidants, aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP) in decane, has been studied with catalytic amounts of all complexes. Finally, biological cytotoxicity studies have also been performed with these oxidovanadium(V) compounds for comparison with cis-dioxidomolybdenum(VI) Schiff base complexes with the same chiral ligands, as well as to determine the cytoprotection against the oxidative damage caused by 30% H2O2 in the HT-22 hippocampal neuronal cells in the range of their 10-100 μM concentration.

Light-Responsive Pt(IV) Prodrugs with Controlled Photoactivation and Low Dark Toxicity.

Light-induced release of cisplatin from Pt(IV) prodrugs represents a promising approach for precise control over the antiproliferative activity of Pt-based chemotherapeutic drugs. This method has the potential to overcome crucial drawbacks of conventional cisplatin therapy, such as high general toxicity toward healthy organs and tissues. Herein, we report two Pt(IV) prodrugs with BODIPY-based photoactive ligands Pt-1 and Pt-2, which were designed using carbamate and triazole linkers, respectively. Both prodrugs demonstrated the ability to release cisplatin under blue light irradiation without the requirement of an external reducing agent. Dicarboxylated Pt-2 prodrug turned out to be more stable in the dark and more sensitive to light than its monocarbamate Pt-1 counterpart; these observations were explained using DFT calculations. The investigation of the photoreduction mechanism of Pt-1 and Pt-2 prodrugs using DFT modeling and ΔG0 PET estimation suggests that the photoinduced electron transfer from the singlet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin from the complexes. Cytotoxicity studies demonstrated that both prodrugs were nontoxic in the dark and toxic to MCF-7 cells under low-dose irradiation with blue light, and the observed effect was solely due to the cisplatin release from the Pt(IV) prodrugs. Our research presents an elegant synthetic approach to light-activated Pt(IV) prodrugs and presents findings that may contribute to the future rational design of photoactivatable Pt(IV) prodrugs.

A facile and scalable method to synthesize PEGylated PDMAEMA for gene delivery.

In recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost-effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO-PDMAEMA-PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream. Two polymers of different molecular weights were synthesized, and polymer/eGFP polyplexes were prepared and characterized. The correlation between polymers' molecular weight and physicochemical properties (size and zeta potential) of polyplexes was investigated. Lipofectamine 2000, a commercial non-viral transfection reagent, was used as a standard control. PEO-PDMAEMA-PEO with higher molecular weight exhibited slightly better transfection efficiency than Lipofectamine 2000, and the cytotoxicity study proved that it could function as a safe gene vector. We believe that PEO-PDMAEMA-PEO could serve as a model to investigate more potential in the gene delivery area.

A Comprehensive Study on Peppermint Oil and Cinnamon Oil as Nanoemulsion: Preparation, Stability, Cytotoxicity, Antimicrobial, Antifungal, and Antioxidant Activity.

Recent studies have shown that nanoemulsions prepared with essential oils have significant antimicrobial potential against multidrug-resistant pathogens due to increased chemical stability. Nanoemulsion also promotes controlled and sustained release, which increases their bioavailability and efficacy against multidrug-resistant bacteria. This study aimed to investigate the antimicrobial, antifungal, antioxidant, and cytotoxicity properties of cinnamon essential oil and peppermint essential oil as nanoemulsions compared to pure forms. For this purpose, analyses of the selected stable nanoemulsions were carried out. The droplet sizes and zeta potentials of peppermint essential oil nanoemulsions and cinnamon essential oil nanoemulsions were found to be 154.6±1.42 nm and -17.1±0.68 mV and 200.3±4.71 nm and -20.0±0.81 mV, respectively. Although the amount of essential oil used in nanoemulsions was 25% w/w, antioxidant and antimicrobial activities were found to be more effective compared to pure essential oils. In cytotoxicity studies on the 3T3 cell line, both essential oil nanoemulsions showed higher cell viability than pure essential oils. At the same time, cinnamon essential oil nanoemulsions exhibited a higher antioxidant property than peppermint essential oil nanoemulsions and showed superiority in the antimicrobial susceptibility test conducted against four bacteria and two fungi. Cell viability tests determined that cinnamon essential oil nanoemulsions showed considerably higher cell viability compared to pure cinnamon essential oil. These findings indicated that the prepared nanoemulsions in the current study might positively influence the dosing regimen and clinical outcomes of antibiotic therapy.

Effect of chemical penetration enhancers on the transdermal delivery of olanzapine in human skin in vitro

This research study involves the development of an olanzapine (OLZ) formulation using various chemical penetration enhancers (CPEs) for transdermal delivery. The aim of this study was to obtain the initial data needed about the effects of various CPEs on the skin permeation of OLZ. The effects of the selected CPEs were examined by studying the permeation profiles of OLZ from formulations applied to human cadaver skin samples. A control formulation of OLZ in propylene glycol (PG) was prepared and compared against formulations containing chemical penetration enhancers. Five different CPEs (oleic acid (OA), cineole (Cin), isopropyl alcohol (IPA), Tween 80 (T80), and N-methyl pyrrolidone (NMP)) at 5% w/w were individually added to the formulation containing OLZ in PG. The in vitro permeation study was carried out using vertical Franz diffusion cells mounted with human cadaver skin. Samples from the receptor compartment of the cell were collected at 2 h, 4 h, 8 h, 12 h, and 24 h at room temperature. The amount (µg/cm2) of permeated drug (OLZ) was measured using a validated HPLC method, and the percentage (%) of OLZ permeated was calculated. Based on the data obtained, different CPEs were found to have a significant impact on OLZ permeability compared to the control formulation. The most effective chemical penetration enhancer was shown to be 5% w/w OA with a 3.3-fold increase in enhancement ratio (ER). The rank of order for the highest concentration of OLZ permeated from each of CPE containing formulation was as follows: OA > Cin > IPA > T80 > NMP. The most effective chemical penetration enhancer was OA but the cytotoxic study using human fibroblast cells suggests that OA may not be safe due to its cytotoxic effects.

Consecutive high-performance removal of Cu2+ metal ions and Deltamethrin using multifunctional pyrolysis cuttlebone/cotton fabric nanocomposite

A simple technique was developed for the modification of cotton materials that is inexpensive, environmentally friendly, and very effective. Waste Cotton fabrics (WCFs) are loaded with propolis extract (PE) for Cu2+ removal. Then, Cu2+ underwent a pyrolysis process with modified cuttlebone (CB) at 900 °C for 5 h. The surface of the prepared materials was characterized using X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray (SEM-EDX), Fourier transform infrared (FTIR), BET, particle sizes, thermogravimetric analysis (TGA) and zeta potential analysis. The Cu2+ metal ions from an aqueous solution were removed using WCFs/PE, and DLM was subsequently removed using pyro WCFs/PE/Cu/CB. The as-prepared NPs exhibited the face-centered cubic structure of WCFs/PE/Cu/CB with crystallite sizes ranging from 386.70 to 653.10 nm. FTIR spectra revealed that CB was present on the surface of the resulting WCFs/PE/Cu. SEM revealed the dispersion of a uniformly flower-like morphology over a large area. Sorption studies were performed based on parameters that included pH, dose, contact time, and initial concentration. The adsorption isotherm and the kinetic studies of the DLM adsorption process were applied at a pH of 5.0 and a temperature of 25 °C using several isotherms and kinetic models. The results revealed qmax (20.51 mg/g) with R2 = 0.97, the Langmuir isotherm that best matches the experimental data. Hence, the Langmuir isotherm suggests that it is the model that best describes sorption on homogenous surfaces or surface-supporting sites with various affinities. The correlation coefficient R2, χ2, adjusted correlation coefficient, and error functions like root mean square (RMSE), normalized root mean square error (NRMES), and mean absolute error (MAE) were used to evaluate the best-fit models to the experimental adsorption data. Moreover, cost estimation for the prepared adsorbent WCFs/PE/Cu showed that it costs approximately 3 USD/g, which is a cheap adsorbent compared to other similar adsorbents reported in the literature. The examined WCFs/PE have significant applicability potential for Cu2+-laden wastewater treatment due to their superior Cu2+ metal ions adsorption capability and reusability.The cytotoxicity and safety study showed that at higher concentrations, it resulted in much less cell viability. Additionally, the removal efficiency of Cu2+ metal ions from synthetic, realistic industrial wastewater using WCFs/PE reached up to 96.29 %, demonstrating good adsorption capability. Thus, there is a huge possibility of accomplishing this and performing well. This study paves the way for the reuse and valorization of selected adsorbents following circular economy principles.Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEnness Calculator (AGREE).

Ultrasonication assisted percolation extraction, isolation, identification and in silico studies of secondary metabolites from Caesalpinia bonduc (L.) Roxb. seeds with special reference to the target proteins involved in Benign Prostatic Hyperplasia

Medicinal plant-derived phytochemicals provide a vast pool of diverse bioactive compounds for novel drug development. Caesalpinia bonduc L. Roxb. is a traditional medicinal plant that is reported for diverse pharmacological properties. This study aims to compare conventional (maceration) and novel extraction techniques (ultrasonication assisted maceration extraction) to evaluate their efficiency, yield and bioactive potential of hydroalcoholic extracts from C. bonduc seeds. Furthermore, the study also aimed to isolate the bioactive compounds from the hydroalcoholic seed extract obtained from ultrasonication assisted maceration and in-silico studies of isolated compounds against the protein targets involved in Benign Prostatic Hyperplasia (BPH). For comparing the influence of extraction methods, the seeds were extracted using a novel and conventional techniques. Chemical profiling, antioxidant activities, cytotoxic and apoptotic studies were conducted using obtained extracts. The extract yielded from the novel technique recorded the highest yield, significant antioxidant activity, cytotoxicity and chemical content when compared to the conventional technique. From the hydroalcoholic extract, three major bioactive compounds, namely ethyl glucoside, methyl lineolate and linoleic acid, were isolated using column chromatography. The structures of the compounds were elucidated on the basis of extensive NMR (1H, 13C, DEPT, 2D NMR- HMBC and HSQC) and HR-ESI-MS analysis. In-silico anti-BPH activity of isolated compounds clearly reveals that the compounds were targeting 5α‒Reductase and α1-Adrenoceptor linked to the BPH progressions. Based on this investigation, it is demonstrated that isolated molecules or active molecule-enriched fractions of C. bonduc should be further researched to confirm the anti-BPH activity through in-depth preclinical and clinical research for the development of products. Ethyl glucoside and methyl lineolate were isolated for the first time from C. bonduc.

Natural carbon incorporated ZnO/C and ZnO: Sustainable nanomaterials for antioxidant, toxicity and cytotoxicity investigations

The innovative synthesis of ZnO/C nanocomposites and pristine ZnO nanoparticles using an ethanol extract of Anodendron parviflorum through various environmentally mediated approaches has been reported for the first time. The oil bath and blue LED mediated synthesis led to the synthesis of O–ZnO/C and B–ZnO/C nanocomposites, whereas the microwave-assisted synthesis yielded pristine M − ZnO nanoparticles. The biosynthesized nanomaterials were analyzed through UV, FE-SEM, HR-TEM, EDX, XRD, AFM, TGA, FTIR, XPS, Raman and zeta potential. The sizes of the O–ZnO/C, B–ZnO/C, and M − ZnO nanomaterials were 14.8, 24.49 and 16.39 nm in XRD. FE-SEM images revealed the spherical morphology of the nanomaterials. XRD, EDX, XPS, and Raman spectroscopy confirmed the presence of carbon derived from the plant in B–ZnO/C and O–ZnO/C, and its absence in M − ZnO nanoparticles. The O–ZnO/C and B–ZnO/C nanocomposites exhibited better antioxidant properties than M-ZnO. Biocompatibility studies revealed that the nanocomposites were more biocompatible than the M-ZnO. Furthermore, the cytotoxic studies showed potent anticancer properties of B–ZnO/C and O–ZnO/C compared to M − ZnO nanomaterials with IC50 values of 28.1 ± 1.3, 39.7 ± 2.5, and 69 ± 2.6 μg/mL for HeLa cell lines and 23.6 ± 2, 30.5 ± 1.9, and 39.3 ± 2.2 μg/mL against A549 cell lines. Therefore, novel nanocomposites are potential pharmaceutical agents for various cancer therapeutics.

Synthesis, Molecular Modeling and Cytotoxicity Study of New 3-Phenyl Coumarin Derivatives against in vitro Cell Lines

In pursuit of more effective cancer treatments, researchers embarked on a study to enhance the coumarin derivative’s therapeutic potential. These compounds, known for their anticancer properties, have faced challenges such as increased toxicity and drug resistance. The research aimed to design, synthesize and assess new 3-phenyl coumarin derivatives specifically for breast and lung cancer treatment. Utilizing 3-oxoacyl-reductase (1T8I), a series of compounds were synthesized from aromatic aldehydes and phenylacetic acid. Among the synthesized 11 compounds that were examined, compounds C01, C04, C05 and C08 had significant cytotoxic effects on both MCF-7 and MRC-5 cell lines. Particularly, compound C08, featuring ethoxy and nitrate substitution, exhibited remarkable potential against both cancer cell lines, emphasizing its promise for further exploration in cancer therapy.

Enzymatic synthesis of biocompatible polypyrrole with enhanced electrochemical properties for supercapacitors

This study focuses on the biocompatible and ecofriendly enzymatic synthesis of conductive polypyrrole (PPy) using mediators for supercapacitor electrode material. The work investigates the effects of various mediator systems on laccase-catalyzed oxidation of pyrrole and is confirmed through Fourier transform infrared spectroscopy (FTIR) and Ultraviolet (UV) visible spectroscopy. The x-ray diffraction (XRD) and transmission electron microscopy (TEM) analysis has revealed that both mediators and laccase can produce crystalline and amorphous PPy with agglomeration of globular-shaped particles. The PPy-ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) demonstrates higher decomposition temperatures, indicating superior thermal stability up to 400 °C. Electrochemical studies such as cyclic voltammetry (CV), galvanometric charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS) revealed that PPy-ABTS possesses good electrochemical properties. Compared to other laccase-mediated materials synthesized PPy in this study, PPy-ABTS exhibits higher specific capacitance values (242 F g−1 by CV at 10 mV s−1 and 153 F g−1 by GCD at 1 A g−1), with a capacitance retention of nearly 90 % after 10000 cycles. Cytotoxicity study shows that PPy-ABTS has an IC50 value of 528 μg ml−1 against human breast adenocarcinoma (MCF-7) cells, indicating its biocompatibility. Consequently, PPy-ABTS emerges as a promising electrode material for high-performance supercapacitors. Its unreported biocompatibility opens up possibilities for diverse biomedical applications.

New Polyether Macrocycles as Promising Antitumor Agents-Targeted Synthesis and Induction of Mitochondrial Apoptosis.

A series of previously unknown aromatic polyether macrodiolides containing a cis,cis-1,5-diene moiety in the molecule were synthesized in 47-74% yields. Macrocycle compounds were first obtained by intermolecular esterification of aromatic polyether diols with α,ω-alka-nZ,(n+4)Z-dienedioic acids mediated by N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC·HCl) and 4-(dimethylamino)pyridine (DMAP). For the synthesized compounds, studies of cytotoxicity on tumor (Jurkat, K562, U937), conditionally normal (HEK293) cell lines, and normal fibroblasts were carried out. CC50 was determined, and the therapeutic selectivity index of cytotoxic action (SI) in comparison with normal fibroblasts was evaluated. With the involvement of modern methods of flow cytometry for the most promising macrocycles, their effect on mitochondria and the cell cycle was investigated. It was found that a new macrocycle exhibits pronounced apoptosis-inducing activity toward Jurkat cells and can retard cell division by blocking at the G1/S checkpoint. Also, it was shown that the synthesized macrodiolides influence mitochondria due to their high ability to penetrate the mitochondrial membrane.