Respective IC50 Values Research Articles

Evaluation of Antioxidant and Anti-Inflammatory Activities of Aqueous Extract of Malva Sylvestris Leaves in Association with Serum Albumin

Malva sylvestris L., commonly known as common mallow, is an herbaceous plant widely used in traditional Algerian medicine for its anti-inflammatory and antioxidant properties. The richness of its leaves and flowers in phenolic compounds is the source of these therapeutic virtues. In Algeria, various remedies based on this species are commonly used in the treatment of inflammation, joint pain, and digestive disorders. Serum albumin is the most abundant protein in blood plasma and plays a key role in regulating oncotic pressure. Its versatile nature also allows it to transport numerous molecules such as fatty acids, hormones, drugs, and metal ions, thus contributing to the proper functioning of essential physiological processes. This study aims to evaluate certain biological activities resulting from the association between serum albumin and the aqueous extract of Malva sylvestris L. leaves. The results obtained highlight a notable antioxidant activity of this association, with respective IC50 values of 3.825 ± 0.422 μg/ml, 296.13 ± 69.33 μg/ml, and 217.9 ± 31.5 μg/ml for the ability to scavenge DPPH, OH, and H2O2 radicals. The mixture exhibits a total antioxidant capacity with an IC50 of 310.5 ± 11.33 μg/ml and a ferric ion reducing power with an IC50 of 42.93 ± 46.38 μg/ml. The ferrous ion chelating ability is evaluated with an IC50 of 137.96 ± 30.07 μg/ml. Regarding the antiinflammatory activity, no stabilizing effect on erythrocyte membranes against osmotic stress, HOCl-induced oxidative stress, and heat was observed with this association. These results clearly demonstrate that the combination of serum albumin and the aqueous extract of Malva sylvestris leaves significantly potentiates the antioxidant properties of the plant. This combination represents a promising source of bioactive molecules and constitutes an interesting therapeutic alternative for the treatment of pathologies related to oxidative stress.

Combined metformin and simvastatin therapy inhibits SREBP2 maturation and alters energy metabolism in glioma

This study aims to explore the inhibitory effects of combined metformin and simvastatin therapy on the malignant progression of glioma. The research specifically examines how the maturation of SREBP2 as a transcription factor affects the expression of GLUT1 and GLUT6 in glioma cells. Additionally, it investigates the impact of this combination therapy on the biological functions and energy metabolism of glioma cells. To assess the functions of GLUT1/6, sh-GLUT1/6 plasmids were employed. The study determined the half-maximal inhibitory concentrations (IC50) of metformin and simvastatin using the CCK-8 assay. Subsequently, the effects of these drugs on glioma metabolism, proliferation, and apoptosis were explored in vitro and in vivo, using drug concentrations significantly lower than their respective IC50 values. The impact of drug treatment on GLUT1/6 and SREBP2 expression levels was also evaluated. The study elucidated the significant impact of GLUT1/6 on glioma cell functions, resulting in decreased glucose uptake. Moreover, it unveiled the regulatory role of SREBP2 in GLUT1 and GLUT6 transcription, alongside revealing differential expression of SREBP2 precursor and mature forms within gliomas. Following combined drug therapy, GLUT1/6 expression decreased, while the precursor form of SREBP2 increased, and mature SREBP2 reduced. This dual-drug treatment effectively modulated glioma cell energy metabolism. Subsequent in vivo experiments affirmed the augmented anti-tumor efficacy of combined drug therapy. Specifically, the synergistic action of metformin and simvastatin reshaped glioma metabolism, curbed malignant proliferation, promoted apoptosis, and demonstrated superior anti-tumor effects both in vitro and in vivo compared to individual administration of metformin or simvastatin. Importantly, the combination therapy achieved these effects at lower doses, rendering it a safer treatment option.

Screening for antimicrobial and antioxidant activities of quinazolinone based isoxazole and isoxazoline derivatives, synthesis and In silico studies.

Two novel series of quinazolinone based isoxazole and isoxazoline hybrid compounds were synthesized from 6-aminoquinazolinone as a key precursor. The title compounds were achieved in synthetic routes via propargylation and allylation reactions of the precursor followed by cyclization with various chloroximes. The new compounds 4a-g and 6a-g were screened for their antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria and two fungi by employing Ampicillin and Itraconazole as standard reference. Among all, the 4-bromosubstituted analogues in isoxazole series 4d and in isoxazoline series 6d demonstrated potent activity against all bacterial and fungal strains compared to Ampicillin as well as Itraconazole. The MIC of these compounds were determined as 0.012μM. The antioxidant investigation revealed that compounds 4f and 6f with dimethyl substitution, exhibited significant activity. Their respective IC50 values were 1.28 ± 0.33, 1.39 ± 0.38µM and 1.07 ± 0.24, 1.10 ± 0.26µM, when compared to Ascorbic acid. The compounds 4g and 6g with dichloro substitution, exhibited promising results with IC50 values were 2.72 ± 0.34µM and 2.78 ± 0.41µM for 4g, and 2.24 ± 0.93µM and 2.45 ± 0.53µM for 6g, respectively. Their antimicrobial and antioxidant activities were authenticated by the molecular docking study against crystal structure of DNA gyrase and NADPH oxidase. The predicted ADME properties of these molecules progressed favourable drug-likeness properties.

Evaluation of Selected Plant Phenolics via Beta-Secretase-1 Inhibition, Molecular Docking, and Gene Expression Related to Alzheimer's Disease.

Background: The goal of the current study was to investigate the inhibitory activity of six phenolic compounds, i.e., rosmarinic acid, gallic acid, oleuropein, epigallocatechin gallate (EGCG), 3-hydroxytyrosol, and quercetin, against β-site amyloid precursor protein cleaving enzyme-1 (BACE1), also known as β-secretase or memapsin 2, which is implicated in the pathogenesis of Alzheimer's disease (AD). Methods and Results: The inhibitory potential against BACE1, molecular docking simulations, as well as neurotoxicity and the effect on the AD-related gene expression of the selected phenolics were tested. BACE1 inhibitory activity was carried out using the ELISA microplate assay via fluorescence resonance energy transfer (FRET) technology. Molecular docking experiments were performed in the human BACE1 active site (PDB code: 2WJO). Neurotoxicity of the compounds was carried out in SH-SY5Y, a human neuroblastoma cell line, by the Alamar Blue method. A gene expression analysis of the compounds on fourteen genes linked to AD was conducted using the real-time polymerase chain reaction (RT-PCR) method. Rosmarinic acid, EGCG, oleuropein, and quercetin (also used as the reference) were able to inhibit BACE1 with their respective IC50 values 4.06 ± 0.68, 1.62 ± 0.12, 9.87 ± 1.01, and 3.16 ± 0.30 mM. The inhibitory compounds were observed to occupy the non-catalytic site of the BACE1. However, hydrogen bonds were found to be present between rosmarinic acid and EGCG and aspartic amino acid D228 in the catalytic site. Oleuropein and quercetin effectively suppressed the expression of PSEN, APOE, and CLU, which are recognized to be linked to the pathogenesis of AD. Conclusions: The outcomes of the work bring quercetin, EGCG, and rosmarinic acid to the forefront as promising BACE1 inhibitors.

Tin(IV) Complexes With 2‐Formylpyridine Thiosemicarbazones: Structural and Cytotoxic Activity Studies on Bacterial, Fungal, and Cancer Cells

ABSTRACTTin complexes, Sn(IV)‐TSC 1·MeOH and Sn(IV)‐TSC 2, with thiosemicarbazones possessing an N2S ligation system [TSC 1 = 4‐(4‐nitrophenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide and TSC 2 = 4‐(2‐methoxyphenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide] were prepared and structurally characterized. These complexes are found in the space groups P and P21/n, respectively, with their tin atoms in octahedral environments established by three chlorine atoms and an anionic thiosemicarbazone ligand. All compounds (20 mg/mL in DMSO) were tested for their antibacterial [against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa] and antifungal [against Aspergillus flavus and Candida albicans] properties. The ligand TSC 2 displayed inhibitions in the S. aureus and E. coli cultures (with zones of 11 and 10 mm, respectively), whereas Sn(IV)‐TSC 1·MeOH and Sn(IV)‐TSC 2 inhibited all bacteria with 11–15 and 14–16 mm, respectively. In the fungal cultures, only Sn(IV)‐TSC 1·MeOH (10 mm) showed an inhibition zone against A. flavus. The ligands' antiproliferative activities were determined against human cancer cells of the lung, breast, liver, and colon, and both ligands afforded the highest activity against the breast MCF‐7 cells. The complexation enhanced the ligands' activities as TSC 1, TSC 2, Sn(IV)‐TSC 1·MeOH, and Sn(IV)‐TSC 2 afforded respective IC50 values of 52.4, 153.7, 18.3, and 63.9 μM. However, against normal baby hamster kidney (BHK) cells, these compounds showed IC50 data of 54.8, 82.7, 16.1, and 15.3 μM, respectively.

Exploring the phytochemicals, antioxidant properties, and hepatoprotective potential of Moricandia sinaica leaves against paracetamol-induced toxicity: Biological evaluations and in Silico insights.

Thirteen components were identified in the methanol extract of Moricandia sinaica leaves (MSLE) through analysis utilizing HPLC-ESI-MS/MS., including flavonoids, anthocyanins, phenolic acids, and fatty acids. The methanol extract of M. sinaica leaves contained total phenolics and flavonoids (59.37 ± 2.19 mg GAE/g and 38.94 ± 2.72 mg QE/g), respectively. Furthermore, it revealed in vitro antioxidant properties as determined by the DPPH and FRAP assays, with respective IC50 values of 10.22 ± 0.64 and 20.89 ± 1.25 μg/mL. The extract exhibited a notable hepatoprotective effect in rats who experienced paracetamol-induced hepatotoxicity. When a dose of 250 mg/kg was given, there was a 52% reduction in alanine transaminase and a 30% reduction in aspartate transaminase compared to the group with the disease. Furthermore, it demonstrated a 3.4-fold, 2.2-fold, and 2.6-fold increase in superoxide dismutase, non-protein sulfhydryl, and glutathione peroxidase, respectively. In addition, it demonstrated a 68% decrease in lipid peroxide levels compared to the group with paracetamol-induced condition. The verification was conducted using a histological study, which identified improved liver histology with a small number of distended hepatocytes. Moreover, in silico studies focused on the enzymes NADPH oxidase, butyrylcholinesterase, and tyrosinase as the targets for the major compounds. In conclusion, MSLE showed promising hepatoprotective and antioxidant activities due to its richness in antioxidant metabolites.

The Antarctic Yeast Sporobolomyces roseus AL103 as a Promising Source of Health-Promoting Biologically Active Compounds

Antarctic yeasts represent a poorly explored source of novel bioactive compounds with antineoplastic activity and a favorable toxicological profile. The present paper presents the newest data on the antiproliferative and antimicrobial potential of extracts obtained from the psychrophilic strain AL103 of the species Sporobolomyces roseus. The capacity of AL103 to grow under different cultivation conditions, including in a bioreactor system with optimal biomass quantities of approximately 6.0 g/L, was demonstrated. A comparative examination of the metabolic profiles (GC-MS-based) of yeast extracts revealed a wide variety of synthesized molecules responsible for the different levels of antineoplastic activity depending on the tissue origin of the malignant cell lines. Concentration response curves were generated by the MTT dye reduction test. The respective IC50 values were extrapolated and found between 35.3 and 163 µg/mL. The antibacterial potential of both extracts was evaluated with the broth microdilution test against four referent pathogenic bacterial strains. The estimated minimal inhibitory concentrations revealed a moderate antibacterial activity. According to the GC-MS results, both extracts are rich in long-chain fatty acids which are known for their antibacterial properties. In conclusion, the Antarctic strain AL103 possesses promising potential for further pharmacological investigations aiming to elucidate its application as a health-promoting food additive or/and as a source of biologically active compounds.

Antimalarial activity of caged xanthone isolated compounds from Cratoxylum sumatranum stem bark: In vitro and in silico approaches

Preliminary research showed that Cratoxylum sumatranum extract and fractions exhibited antimalarial activity. Two caged xanthone compounds identified as cochinchinone D and cochinchinoxanthone were disengaged from an active portion of the stem bark of C. sumatranum. The purpose of this study is to determine the antimalarial activity of both compounds against Plasmodium falciparum and their in silico prediction on several food vacuole enzymes. Lactate dehydrogenase assay was used to regulate the antimalarial activity, and in silico molecular docking was carried out with a number of receptors, including plasmepsin-II, M1-alanyl aminopeptidase, and falcipain-3. Absorption, distribution, metabolism, excretion, and toxicity (ADME-T) prediction was also conducted for both compounds. The inhibitory concentration (IC50) value for antimalarial activity determination was conducted by probit analysis using GraphPad Prism Version 6.0. Cochinchinone D and cochinchinoxanthone were found to have antimalarial activity, with respective IC50 values of 4.79 µM and 4.41 µM, respectively. Cochinchinone D has a higher affinity for binding to plasmepsin-II, according to in vitro findings. Meanwhile, cochinchinoxanthone and chloroquine as standard have a better affinity to alanyl aminopeptidase. Both compounds have similar ADME-T profiles. Cochinchinone D and cochinchinoxanthone have a high antimalarial activity possibly through the mechanism of inhibition on plasmepsin-II, falcipain-3, and M1-alanyl aminopeptidase enzymes in food vacuole. Both caged compounds have the potential for further development as antimalarial.

Systemic administration of a potent mouse monoclonal antibody provides multisite protection against HPV16 infection

Although preventive vaccines for Human Papillomaviruses (HPV) are available, a definitive cure for the viral infection itself is currently lacking. There is a sizable population that remains inaccessible to HPV vaccination due to reasons such as high costs or lack of availability of the vaccines. Therefore, there remains a significant population susceptible to HPV infection. Persistent multisite infections with high-risk HPV types can cause cancer at several different anatomic sites.Especially HPV16 is a key etiologic factor for cervical, other ano-genital and oropharyngeal cancers. Therefore, it is imperative to develop pharmaceutical interventions for the treatment of viral infections. In this study, a panel of 9 neutralizing antibodies was screened using the hybridoma technique, with 20F6 being identified as the representative antibody. The purified 20F6 exhibited an IC50 of 0.0011 μg/ml against HPV16, demonstrating potent viral inhibitory activity. Moreover, it displayed cross-neutralizing efficacy towards other Alphapapillom 9 subtypes including HPV31, HPV33, HPV52, and HPV58 with respective IC50 values of 2.0 μg/ml, 7.3 μg/ml, 1.7 μg/ml, and 3.0 μg/ml. 20F6 recognizes the linear epitope MSLW, the first four amino-acids located at the very N-terminus of the HPV16 L1 protein. Administration of 20F6, 24 h prior to and following HPV16 pseudo-virion (PSV) challenge, conferred protection against infection in mice at doses as low as 1 mg/kg. Following intraperitoneal administration of 20F6, neutralizing antibodies were consistently detected at both oral and vaginal sites, indicating that prophylactic systemic administration of 20F6 may confer efficient protection against multiple susceptible mucosal sites.

Integrated assessment of phytochemicals, Antilipase, hemoglobin antiglycation, antihyperglycemic, antifungal and antibacterial properties of vetiveria zizanioides (L.) Nash

ABSTRACT Vetiveria zizanioides, known as vetiver grass, is renowned for its ecological significance in soil erosion control and the restoration of lands polluted by heavy metals. Additionally, this plant is extensively harvested for vetiver oil, widely utilized in both medicine and perfumery. The study was designed to investigate the phytochemicals, antilipase, hemoglobin antiglycation, antihyperglycemic, antifungal, and antibacterial properties of V. zizanioides. The GC-MS analysis revealed the presence of various volatile compounds, among which the most predominant ones, which are, 4,6,6-Trimethyl-2-(3-methylbuta-1,3-dienyl) −3-oxatricyclo [5.1.0.0(2,4)] octane, Cycloisolongifolene (8,9-dehydro-), and 9 H-Cycloisolongifolene (8-oxo-). It is noteworthy that this essential oil has shown significant inhibitory activity against α-amylase, α-glucosidase, pancreatic lipase, and glycation, with respective IC50 values of 0.47 ± 0.01, 0.42 ± 0.004, 0.58 ± 0.008, and 0.49 ± 0.005 mg/mL. Additionally, the antimicrobial activity of EoVZ was assessed against a diverse spectrum of Gram+ and Gram- bacteria, as well as fungi, using both disc-diffusion and broth-microdilution techniques. The results showed significant antimicrobial effects against all tested microorganisms, with inhibition zones ranging from 28.33 ± 1.66 mm to 9.0 ± 0.0 mm for bacteria and from 22.5 ± 1.7 mm to 14.0 ± 0.3 mm for fungi. Moreover, minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), and minimum fungicidal concentrations (MFC) were determined, with values ranging from 0.0625% to 2.0% (v/v) for bacteria and from 2.0% to 8.0% (v/v) for fungi. The MBC/MIC and MFC/MIC ratios indicated bactericidal and fungicidal mechanisms. This study underscores the prominent attributes of EoVZ, particularly its antimicrobial and antidiabetic properties, suggesting its potential as a natural and effective agent ensuring high safety standards for public health.

Sodium Butyrate (NaB) and Sodium Propionate (NaP) Reduce Cyclin A2 Expression, Inducing Cell Cycle Arrest and Proliferation Inhibition of Different Breast Cancer Subtypes, Leading to Apoptosis.

Sodium butyrate (NaB) and sodium propionate (NaP) have recently garnered attention for their role in regulating inflammation and controlling signaling pathways of cell growth and apoptosis, potentially preventing cancer development. However, their therapeutic effect and the underlying mechanisms involved remain elusive in breast cancer. This study aims at investigating the anticancer role of NaB and NaP in different types of breast cancer by assessing their antiproliferative effect on MCF-7 and MDA-MB-231 cells (through an MTT assay), as well as their ability to alter the cell cycle and cyclin expression (using flow cytometry and RT-qPCR, respectively), and to promote apoptosis (using Annexin V-FITC conjugated and sub-G1 phase techniques). MDA-MB-231 cell proliferation was inhibited by NaB and NaP in a dose- and time-dependent manner with respective IC50 values of 2.56 mM and 6.49 mM. Treatment induced cell arrest in the G1 phase which was further supported by the significant reduction in cyclin A2 and cyclin B1 expressions. Finally, NaB, and less significantly NaP, induced apoptosis in a dose-dependent manner with higher concentrations required for MDA-MB-231 than MCF-7. Our findings elucidate the cyclin-dependent inhibitory effect of NaB and NaP on the progression of different breast cancer subtypes, thus highlighting their therapeutic potential in breast cancer.

Empagliflozin demonstrates cytotoxicity and synergy with tamoxifen in ER-positive breast cancer cells: anti-proliferative and anti-survival effects.

Accumulating evidence suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors may be effective at eliminating tumor cells. While empagliflozin exhibits nearly the highest selectivity for SGLT2 over SGLT1, its specific impact alone and in combination with tamoxifen remains largely unexplored in estrogen receptor α-positive (ERα +) breast cancer. This study investigated the anticancer effects of empagliflozin and its potential synergy with tamoxifen in MCF-7 breast cancer cells. The individual and combined cytotoxic effects of empagliflozin and tamoxifen were assessed using the xCELLigence system. The activities of AMP-activated protein kinase α (AMPKα), p38 mitogen-activated protein kinase (p38 MAPKα), p70-S6 kinase 1 (p70S6K1), and protein kinase B (Akt) were assessed using Western blotting. The gene expression levels of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and Forkhead box O3a (FOXO3a) were assessed via qPCR. Our results revealed time- and concentration-dependent cytotoxic effects of empagliflozin and tamoxifen whether administered separately or in combination. While tamoxifen exhibits potency with an IC50 value of 17 μM, approximately ten times greater than that of empagliflozin (IC50 = 177 μM), synergistic effects are observed when the concentrations of the two agents approach their respective IC50 values. Additionally, empagliflozin significantly increases AMPKα activity while concurrently inhibiting Akt, p70S6K1, and p38 MAPKα, and these effects are significantly enhanced when empagliflozin is combined with tamoxifen. Moreover, empagliflozin modulates the gene expression, downregulating PGC-1α while upregulating FOXO3a. Empagliflozin exerts anti-proliferative and anti-survival effects by inhibiting mTOR, Akt, and PGC-1α, and it exhibits synergy with tamoxifen in MCF-7 breast cancer cells.

Comparative Study of Essential Oils from Tunisian Pinus Halepensis Mill. by Hydrodistillation and Microwave-Assisted Processes: Chemical Composition and Antioxidant and Cytotoxic Potential against Prostate and Cervical Cancer Cells.

Pinus halepensis Mill. is a Mediterranean aromatic plant largely used, in addition to its nutritional value, in traditional medicine as antiseptic, antifungal, antituberculotic, and antirheumatic. Thus, the objective of this work was to appraise the antioxidant and cytotoxic activity of the essential oil (EO) of P. halepensis from Tunisia on cancer cell cultures, along with chemical composition evaluation by GC-MS. To attain the best yield and also highest quality in extraction of the EOs, conventional hydrodistillation (HD) and novel microwave-assisted extraction (MAE) methods have been performed and compared. The antioxidant activity was evaluated through the inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH)• radicals. The cytotoxic activity in prostate cancer cells (LNCaP and PC3) and cervical cancer cells (HeLa) of EO was evaluated by the MTT assay and effect on the cell cycle by flow cytometry analysis. A total of 38 and 37 components were identified from HD (HD-EO)- and MAE (MAE-EO)-extracted EOs, respectively, which were dominated by hydrocarbon compounds (HD-EO = 86.65%; MAE-EO = 77.36%), especially monoterpenes (HD-EO = 32.11%; MAE-EO = 21.55%) and sesquiterpenes (HD-EO = 44.29%; MAE-EO = 61.32%). Both extracted EOs showed significant antioxidant activity, as shown by the inhibition of DPPH• radicals [IC50 (HD-EO) = 4102.30 ± 159.73 μg mL-1 and IC50 (MAE-EO) = 3430.13 ± 78.46 μg mL-1]. Also, the EOs exhibited substantial (p < 0.001) antiproliferative activities with G0-G1 arrest on PC3, LNCaP, and HeLa cells by yielding very low IC50 values more conspicuous in MAE-EO with respective IC50 values of 25.70 ± 6.58, 14.97 ± 3.21, and 14.55 ± 2.30 μg mL-1. This finding points out for the first time that the EO of P. halepensis Mill. from Tunisia can be an effective natural antitumor agent with more pronounced activity when extracted with the MAE method that, after further in vivo studies, can be harnessed as a putative phytopharmaceutical for prostate and cervical cancer treatment.

Green Synthesis of Silver Nanoparticles With Cyclosorus dentatus and Nephrolepis biserrata and Their Antioxidant, Anti‐Inflammatory Studies

ABSTRACTThis study examined the synthesis of silver nanoparticles (SNPs) with aqueous extracts of Cyclosorus dentatus and Nephrolepis biserrata fronds and the evaluation of their biological activities. Mixing of AgNO3 solution and the aqueous extracts resulted in color change, indicating the formation of SNPs. UV‐Vis spectroscopy analysis gave a surface plasmon resonance (SPR) peak at approximately 420 nm, confirming the presence of the synthesized SNPs. Infrared analysis showed C‐O, N‐O, and C‐C vibrations or stretching and aliphatic vibrations of hydrocarbon chains of the synthesized SNPs. x‐Ray diffraction (XRD) analysis indicated the SNPs were face‐centered, cubic, and crystalline in nature, with crystallite sizes. The scanning electron microscopy (SEM) shows the aggregation of the spherical shape nanoparticles. The SNPs significantly reduced phosphomolybdenum and captured H2O2 with respective IC50 values of 61.55 and 29.03 µg/mL for C. dentatus SNP (SNP‐Cd), and 92.61 and 9.07 µg/mL for N. biserrata SNP (SNP‐Nb), respectively. In terms of albumin‐denaturing activity, the SNPs gave an IC50 value of 21.20 µg/mL for SNP‐Cd and 7.18 µg/mL for SNP‐Nb. Thus, this work confirmed that SNP‐Cd and SNP‐Nb are potential therapeutic agents for treating oxidative stress, inflammatory problems, and related diseases.

Hydrazinated geraniol derivatives as potential broad-spectrum antiprotozoal agents.

Geraniol, a primary component of several essential oils, has been associated with broad-spectrum antiprotozoal activities, although moderate to weak. This study primarily concentrated on the synthesis of hydrazinated geraniol derivatives as potential antiprotozoal agents. The synthesised compounds were tested in vitro against different parasitic protozoans of clinical relevance, including Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania infantum. Compounds 6, 8, 13, 14 and 15 demonstrated low micromolar activity against the different parasites. Compounds 8, 13, 14 and 15 had the highest efficacy against Trypanosoma brucei rhodesiense, as indicated by their respective IC50 values of 0.74, 0.56, 1.26 and 1.00 µM. Compounds 6, 14 and 15 displayed the best activity against Trypanosoma brucei brucei, with IC50 values of 1.49, 1.48 and 1.85 µM, respectively. The activity of compounds 6, 14 and 15 also extended to intracellular Trypanosoma cruzi, with IC50 values of 5.14, 6.30 and 4.90 µM, respectively. Compound 6, with an IC50 value of 11.73 µM, and compound 14, with an IC50 value of 8.14 µM, demonstrated some modest antileishmanial activity.

Synergistic anticancer effects of omega-3 fatty acids (EPA/DHA) and anticancer drug Doxorubicin against human lung adenocarcinoma

Single agent therapy in the treatment of cancer did not provide satisfactory clinical outcome in a long term due to drug resistance, cumulative toxicity and suboptimal efficacy. Therefore, combination therapies are apt to improve the quality of life in patients. In the present study, combinatorial effect of EPA and/or DHA with doxorubicin (Dox) was evaluated for their potential synergistic effect on human lung adenocarcinoma (A549) cells. The respective IC50 values obtained for EPA, DHA and Dox were 170, 140 and 2.5 μmol/L and thus EPA and DHA were separately combined with Dox at constant ratio of 68:1 and 56:1 respectively, depending on the ratio of their IC50 values. Different combinations of drugs revealed dose-dependent inhibition of cell viability and IC50 values were reduced to nearly 3-fold (58.75 μmol/L) and 4.5-fold (31.5 μmol/L) in EPA-Dox and DHA-Dox combination respectively. Combination index (CI) revealed strong synergism (CI < 0.5) in DHA-Dox (0.49) and moderate synergism (CI > 0.5) in EPA-Dox (0.79) at 0.5 Fa (Fraction affected), which is further confirmed by dose reduction index and isobologram. The mechanisms underlying synergistic interactions involve intracellular ROS generation and MMP depolarisation which causes changes in the cell morphology viz. Nuclear fragmentation/condensation, membrane blebbing and early/late apoptotic cells. Moreover, cell cycle arrest was observed at the S and G2/M phase, with more prominent effect in G2/M phase. No toxicity was imposed on non-cancerous HEK-293 T cells. These findings suggest that EPA-Dox and DHA-Dox could be explored further for animal studies and clinical trials for lung adenocarcinoma treatment.

Combination treatment of Clinacanthus nutans extract with cisplatin against breast cancer cell line, MCF-7

Chemotherapy is one of the treatments for cancer and among the important agent is cisplatin. However, owing to the adverse effects associated with modern medicine, patients often explore traditional herbal remedies for cancer management. Clinacanthus nutans is widely believed to possess healing properties for various ailments, including cancer. The cultural and traditional background of this plant increases its acceptance among patients seeking alternative or complementary treatments. There exists a growing concern regarding the potential impact of C. nutans on the efficacy of cisplatin in treating breast cancer. Thus, this study aims to assess the anticancer properties of C. nutans water extract on MCF-7 cells and examine the interaction between C. nutans water extract and cisplatin on MCF-7 cells. Cells were treated separately with C. nutans water extract or cisplatin to determine their respective IC50 values. Subsequently, a combination treatment involving C. nutans water extract and cisplatin was administered, and the percentage of MCF-7 cell viability was assessed using MTT assay. The findings indicate that C. nutans water extract exhibits limited anticancer activity on MCF-7 cells and demonstrates an antagonistic interaction with cisplatin on MCF- 7 cells. Further research is warranted to explore potential interactions between C. nutans and other anticancer agents, thereby paving the way for more informed approaches in cancer treatment.

Two alkenyl phenol derivatives from the fungus Pestalotiopsis clavata JSQ 12 isolated from the mushroom Lanmaoa asiatica

Two new alkenyl phenol derivatives, namely pestalol F (1) and pestalol G (2), along with two known compounds, pestalachloride A (3) and pestalotiopsin J (4), were isolated from the culture of the fungus Pestalotiopsis clavata JSQ 12. The structures of these compounds were primarily elucidated by MS, NMR and specific rotation data analysises. These secondary metabolites of Pestalotiopsis clavata were reported for the first time. Compound 2 displayed interesting cytotoxic activity against MCF-7 cell line with the IC50 value of 29.16 μM, whereas compound 3 exhibited moderate activity towards A549 cell line with the IC50 value of 35.71 μM. The positive control 5-FU showed cytotoxic effects on MCF-7 and A549 cell lines with the respective IC50 values of 26.70 and 26.07 μM. Compounds 1 and 2 displayed mild antibacterial activities against Staphylococcus aureus with MIC values of 128 and 64 μg/mL (MIC of positive control, penicillin, was 0.016 μg/mL), respectively.

Synthesis, characterisation, X-ray diffraction and biological evaluation of new thiourea derivatives against Mycobacterium tuberculosis and cervical cancer

In this study, thiourea derivatives were prepared to identify potentially effective compounds against tuberculosis and cervical cancer. The newly synthesized compounds, namely N-(cyclohexyl(methyl)carbomothioyl) benzamide (TU1), N-(cyclohexyl(methyl)carbamothioyl)-2-methylbenzamide (TU2), N-(dicyclohexylcarbamothioyl) benzamide (TU3), N-(dicyclohexylcarbamothioyl)-4-nitrobenzamide (TU4), N-(diphenylcarbamothioyl) benzamide (TU5), and N-(diphenylcarbamothioyl)-4-nitrobenzamide (TU6), were obtained in high purity and yields. The compounds were successfully characterized by infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance (NMR), single crystal X-ray diffractometer (SCXRD), mass spectrometry (MS) and the melting points (mp). Crystal structure analyses of TU1, TU2 and TU6 were carried out which showed, that in the solid state, the molecules were linked together by intermolecular hydrogen bonds, specifically NH⋯S and CH⋯O interactions. In-vitro testing against M. tuberculosis (Mtb) revealed compounds TU1 and TU2 to be the most potent with MIC90 values of 28.2 and 11.2 μM, respectively. However, compounds TU4, TU5, and TU6, with MIC90 values of 80.3, 82.8 and 107.7 µM, respectively, exhibit mild antituberculosis activity, whereas TU3 with a MIC90 value of 752.7 µM is considered inactive against the Mtb strain. None of the compounds demonstrated significant selectivity for bacterial cells versus human cells and thus further studies could be dedicated to creating derivatives of TU1 and TU2 that are more selective. In vitro biological screening against HeLa cells revealed two highly toxic compounds, TU2 and TU6, with respective IC50 values of 12.00 ± 1.21 μM (SI = 1.06) and 8.45 ± 1.21 μM (SI = 0.08); and two moderately toxic compounds, TU4 (IC50 = 27.75 ± 1.15 µM; SI = 0.35) and TU5 (IC50 = 23.66 ± 1.24 µM; SI = 0.29).

Effectiveness of Using Gum Arabic for Co-Microencapsulation of Ruellia tuberosa L. and Tithonia diversifolia Extracts as Encapsulating Agent and Release Studies.

This study used a combination of leaves extracts from Ruellia tuberosa L. and Tithonia diversifolia plants encapsulated using gum Arabic. The selection of leaves in medicinal plants because they are rich in bioactive compounds that provide health benefits. The encapsulation technique was microencapsulation through freeze-drying, since the nanoencapsulation for the plant extracts is unlikely to be conducted due to their large particle sizes. The resulting microcapsules were then tested their biological activities in vitro. Several conditions affect microcapsules' production, including pH, gum Arabic concentration, and stirring time were assessed. The optimum conditions were chosen based on the highest encapsulation efficiency. The results showed that the optimum microcapsules preparation was achived at pH 5, gum Arabic concentration of 4% (w/v), and stirring time of 60 min with an encapsulation efficiency of 84.29%. The in vitro assays include inhibition of alpha-amylase and antioxidant activities, resulted in the respective IC50 values of 54.74 μg/mL and 152.74 μg/mL. Releases of bioactive compounds from the microcapsules were investigated under pH 2.2 and pH 7.4 from 30 to 120 min. Results indicated a release of 43.10% at pH 2.2 and 42.26% at pH 7.4 during 120 min, demonstrating the controlled release behavior of the encapsulated bioactive compounds; nonetheless, their release behavior was not pH-dependent. This study confirms that microencapsulation has an important role in the development of plant extracts with maintained biological functions as well as maintaining their stability.