Indonesian Journal of Pharmacy
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Cytotoxic and Computational Profiling of 20 Indole Alkaloids Across Five Breast Cancer Cell Lines
No full textIndole alkaloids are a structurally diverse class of natural compounds known for their potent anticancer properties, including the ability to induce apoptosis and inhibit cell proliferation and metastasis. This study aimed to evaluate the cytotoxic potential of 20 indole alkaloids against breast cancer cell lines, investigate their molecular interactions with five key cancer-related proteins (Bcl-2, Caspase-3, CDK4, NF-κB, and MMP-9), and assess their pharmacokinetic and toxicity profiles. Cytotoxicity was tested using the MTT assay across five breast cancer cell lines: MCF-7, T47D, MDA-MB-231, BT-474, and 4T1. Vincristine exhibited the most potent cytotoxicity (IC₅₀: 0.05–0.10 µM), followed by vinblastine and camptothecin. Triple-negative breast cancer (TNBC) cells demonstrated higher resistance compared to luminal subtypes, indicating subtype-specific drug responses. Structure–activity relationship analysis revealed that the presence of lactone rings and hydrophobic side chains enhanced cytotoxic activity. Molecular docking using AutoDock 4.2 identified irinotecan, sanguinarine, and piperine as top binders, with binding affinities ranging from –8.5 to –10.9 kcal/mol. Molecular dynamics simulations confirmed the stability of ligand–target interactions (RMSF < 3 Å). ADMET predictions using SwissADME and pkCSM indicated that all three compounds possessed favorable drug-like properties and high gastrointestinal absorption, though sanguinarine and piperine showed potential mutagenicity or carcinogenicity. The integrated in vitro and in silico approach supports the further exploration of irinotecan, sanguinarine, and piperine as promising multi-target anticancer agents. Notably, tylophorine and vincristine also emerged as potent candidates with favorable pharmacological profiles, warranting further preclinical validation for breast cancer therapy
The Application Arbutin in Elimination Resistance of Antibiotics Against Gramm-Negative Multi-Drug Resistance Bacteria of Acinetobacter baumanni and Klebsiella pneumoniae
Get PDFThe purpose of our work was investigate in vitro and in silico elimination resistance of antibiotics against clinical multidrug-resistant strains of A. baumani, K. pneumonia by arbutin. The molecular docking was performed using AutoDockTools 1.5.6; antimicrobial effects were evaluated by the well method. Theoretical studies have found that none of the investigated antibiotics and arbutin highly selectively inhibits all "targets" mechanisms of antimicrobial action. In experimental studies, it was observed that the addition of arbutin to the antibiotic led to the emergence of sensitivity on the part of resistant strains. All Gramm-negative resistance strains of bacteria were sensitive to the action of arbutin. Moreover, arbutin increased the antimicrobial effect of antibiotics from 8 to 55%. It was estimated exceptions such as clarithromycin and azithromycin when assessing antimicrobial activity against A. baumani and P. aeruginosa. These studies haves shown that to inhibit resistant strains of bacteria, require the use of combinations of “classical” antimicrobials and herbal drugs or dietary supplements based on extracts obtained from arbutin-containing medicinal plants such as lingonberry, bearberry, and cranberry. This approach is a “lifeline” for the development of antimicrobial agents against resistant bacteria and gives “a second chance to return to life” for outdated antibiotics
Computer-aided Discovery of Bioactive Natural Product Isoliquiritigenin as an Acetylcholinesterase Inhibitor
Get PDFBioactive natural products have been extensively investigated for the discovery of alternative Alzheimer’s disease (AD) treatments. Recently, our structure-based virtual screening (SBVS) campaigns on natural products served in the LOTUS database exhibited the potency of isoliquiritigenin as an acetylcholinesterase (AChE) inhibitor, which propelled us to investigate it further. This study aimed to evaluate the acetylcholinesterase (AChE) inhibitory activity of isoliquiritigenin compared to commonly known inhibitors i.e., donepezil through in vitro and in silico studies. The AChE inhibitory activity of isoliquiritigenin and donepezil was evaluated using the improved Ellman method and the molecular mechanism in inhibiting AChE was identified using molecular docking and dynamics simulations. Our findings verified the AChE inhibitory activity of isoliquiritigenin, possessing an IC50 value of 126.22 µM compared to donepezil with an IC50 value of 36.98 µM. In silico studies revealed that five best-docked poses from 100 redocking and molecular docking simulations established interactions in the AChE active site in 5 ns after 5-ns equilibration run. Further dynamics interactions were explored to 50 ns, showing interactions of isoliquiritigenin and donepezil which were still in the AChE active site. These simulations also revealed the pivotality of the aromatic ring and hydroxyl moiety of isoliquiritigenin reinforcing the receptor-ligand stabilization. Our studies hence exhibited the potency of isoliquiritigenin acting as an AChE inhibitor and might be explored in isoliquiritigenin-containing bioactive natural products as AD alternative treatments.  
In Vitro Evaluation of 4-Methoxyresorcinol and Kaempferol 7-ORutinoside and Their Radioiodinated Derivatives in MCF-7, MDA-MB-231, and LNCaP Cell Lines
Get PDFThe global population is currently experiencing high rates of mortality due to the growing burden of cancer. Efforts on the development of new potent anticancer agents are necessary. Therefore, this study aimed to evaluate the anticancer activity of two flavonoids, including 4-methoxyresorcinol (MRC) and kaempferol 7-O-rutinoside (K7R), isolated from Melia azedarach L. leaves. Anticancer activity was evaluated in vitro against MCF-7, MDA-MB-231, and LNCaP cell lines. Radioiodination was performed with iodine-131 as well as computational studies to assess the feasibility of the isolated compounds as natural product-based radiopharmaceuticals for diagnosing and managing cancer. The results showed that MRC and K7R had moderate anticancer activity against MCF-7, MDA-MB-231, and LNCaP cell lines with IC50 values ranging from 154.75 to 1962.66 µM. Cellular uptake investigations found that the highest cellular accumulation of [131I]-4-methoxyresorcinol (MRCI) was observed in MCF-7 (3.17 ± 0.11%) after 24 hours of incubation, approximately 20-fold greater than the control group uptake (iodine-131). Meanwhile, [131I]-kaempferol 7-O-rutinoside (K7RI) showed the highest uptake in MCF-7 (3.05 ± 0.9%) post-one hour of incubation, which was around 23-folds higher than iodine-131 uptake. In conclusion, both MRC and K7R were identified as potential anticancer drugs, which could be further developed into new radiopharmaceutical candidates
Factors Affecting Preparation of Repaglinide Nanoparticles for Dissolution Improvement
No full textThis study aimed to develop a stable nanosuspension of repaglinide and improve its dissolution, using the Nano-precipitation method, involving a different concentration of a stabilizer, different co-stabilizers and different solvents. Employment of a systemic approach to optimize the formulation parameters, including stabilizer concentration, solvent choice and co-stabilizer election. Soluplus® (SOL) was used as the primary stabilizer for this research, polyvinyl alcohol (PVA), poloxamer 188 (PXM 188), tween 80 (TW80), and polyvinyl pyrrolidine (PVP k30) were investigated as co-stabilizers to prevent particle agglomeration and ensure long-term stability. In addition to ethanol as a primary solvent, acetone and chloroform were used for solvent-change assessment. Particle size, polydispersity index (PDI), FTIR study to reveal any interactions and particle morphology using scanning electron microscope, and drug crystallinity and thermal changes were evaluated to assess the physicochemical properties of the nanosuspension.
RPG-SOL3 resulted nanoparticle mean size (82.96 nm±3.95) and a PDI of (0.100±0.098). In vitro dissolution studies showed a complete dissolution of the formula and a significant enhancement when compared to RPG drug powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the amorphous nature of optimal RPG nanoparticle. This study successfully develops a stable nanosuspension formulation of repaglinide to improve its dissolution properties. We have achieved a nanosuspension with desirable physicochemical characteristics through systematic optimization of formulation parameters, including selecting stabilizers and co-stabilizers
Antidiabetic Potential and Phytochemical Profiling of Leea indica Leaves: In Vitro and In Silico Analysis
No full textLeea indica is a medicinal plant native to tropical Asia, which has been traditionally used to treat various diseases, including diabetes. Therefore, this study aims to investigate the antioxidant, alpha-glucosidase, and alpha-amylase inhibitory activities of L. indica leaf ethanol extract and identify the bioactive compounds using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The extract prepared through maceration with 96% ethanol produced an extraction efficiency of 3.52%. Phytochemical screening showed the presence of alkaloids, flavonoids, saponins, tannins, quinones, and steroids/triterpenoids. The extract had strong antioxidant activity (IC50 = 18.691 ± 0.05 µg/mL) as well as high total phenolic (6.957 ± 0.09 g GAE/100 g) and flavonoid (32.917 ± 0.07 g QE/100 g) contents. Additionally, the extract had potent alpha-glucosidase (IC50 = 7.90 µg/mL) and alpha-amylase (IC50 = 30,663.89 µg/mL) inhibitory activities. LC-MS/MS analysis identified 11 bioactive compounds, including phenylacetic acid (60.89%), shikimate (10.89%), kaempferol (3.67%), and quercetin (2.27%). In silico molecular docking studies showed that 4-[(2s,3s)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxyphenol had a strong binding affinity with key residues in alpha-glucosidase, and 5-(acetyloxy)-2,4-dihydroxy-6-methyloxan-3-yl 3-(4-hydroxyphenyl)prop-2-enoate reacted significantly with crucial residues in alpha-amylase. These results support the traditional use of L. indica in diabetes management and show the potential as a source of natural antidiabetic agents. Further in vivo studies and toxicity tests are necessary to confirm the efficacy and safety for human use
Assessing the Impact of the AKU-DEMEN Collaborative Dementia Application on Patient Therapy Outcomes and Caregivers' Quality of Life and Satisfaction
No full textDementia is a global health problem, with cases increasing every year. Dementia therapy aims to prevent worsening so patients maintain cognitive function, activity, and quality of life. However, the disease is irreversible with a poor prognosis and requires complex care, making it a challenge to overcome. Interprofessional Collaboration (IPC) is an essential aspect of treatment, but effective collaboration frameworks are lacking. This study aims to analyze the impact of using the AKU-DEMEN application on patient therapy outcomes, both from the aspects of cognitive function, level of independence, quality of life of patients and their caregivers, and user’s satisfaction with using the application at the Memory Clinic of Dr. Sardjito Hospital. This study employed a quasi-experimental, one-group pretest-posttest design to evaluate the application's effectiveness in 80 eligible respondents. The instruments used included MoCa-Ina, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), DEMQOL-proxy, WHOQOL-BREF, and paired sample t-test for data analysis. The level of caregiver’s satisfaction was measured with the Customer Satisfaction questionnaire and qualitative analysis using NVIVO 12 Plus. The results showed that the AKU DEMEN application was effective in maintaining therapy outcomes, both from the aspects of cognitive function, level of independence, and quality of life of patients, with no significant decrease (p-value ≥ 0.05) before and after using the application, as well as improving the quality of life of caregivers, especially in the psychological and social domains. The level of caregivers reached 79.22% (satisfied category), with the interprofessional collaboration message feature as the main advantage. In conclusion, the app provides significant benefits in supporting dementia care and is expected to continue to be used in clinical practice
Risk Factors of Symptoms Occurrence in SARS-CoV-2 Infection After Implementing Vaccination Program in Bali
Get PDFThe real-world data have shown the effectiveness of many variants of Covid-19 vaccines. However, many people still get infected and indicate various symptoms after vaccination. This study aims to assess the risk factors of symptom occurrence in Covid-19 after implementing the vaccination program in Bali. This retrospective, case-control study used surveillance data include demographic, vaccination status, symptom occurrence, and severity from Pemecutan Kaja Village, North Denpasar district. Participants were included if they tested positive for SARS-CoV-2 with a minimum age of 18 years old. There was a total of 592 data on Covid-19 patients, the cases group was symptomatic and the control group was asymptomatic. Between May to September 2021, the vaccination program was implemented in Bali with Sinovac and Astra Zeneca. The risk factor analysis showed that age (OR 2.57, 95% CI 1.376-4.818; p = 0,003) and vaccination status (OR 3.104, 95% CI 2.089-4.611; p = < 0,001) were associated with symptom occurrence in Covid-19. Elderly and unvaccinated subjects have a higher risk of developing symptomatic SARS-CoV-2 infection. Vaccinations were not 100% effective in protecting people from infection, but almost all symptoms were reported as less frequent in vaccinated. A better understanding of the risk factor of severe infection has apparent implications for additional prevention and treatment for those with a higher risk of developing the severe condition. Adopting strategies are required to facing the probability of infection and controlling any future epidemic
Complexes of Pentagamavunon-1 and Lactosylated Albumin for Enhancing the Cytotoxic Effect on Hepatocellular Carcinoma
No full textPGV-1 exhibits potential as an anticancer drug for hepatocellular carcinoma (HCC), and this study focuses on enhancing its solubility and cytotoxicity against liver cancer cells. To achieve this, complexes were developed by combining Bovine Serum Albumin (BSA) with lactose, aiming to improve the bioavailability of PGV-1 as an anticancer agent. Subsequently, these complexes were further modified through lactosylation, resulting in PGV-1-loaded lactosylated BSA (PGV-1+BSA+Lac), with the purpose of increasing their cytotoxic effects on HCC cells. The glycation of BSA with d-lactose was conducted under dry-heat conditions at 60°C for various durations (0, 30, 60, 120, or 240 minutes). Monitoring the extent of BSA glycation involved assessing the availability of free peptide and examining the molecular weight profile. A straightforward formulation was proposed, involving the complexation of BSA lactosylated with PGV-1. The solubility of PGV-1 in aqueous solutions was assessed with varying amounts of BSA. Cytotoxicity was evaluated through an MTT assay using the HLF liver cancer cell line. The results revealed distinct variations in BSA conjugation depending on the duration of heating. Modified BSA exhibited reduced peptide availability and slower migration in SDS/PAGE. Notably, PGV-1 demonstrated significantly higher solubility when combined with BSA+Lac, as compared to PGV-1+BSA. The IC50 values for PGV-1+BSA+Lac in HLF cells (0.008±0.002 µM) were markedly lower than those for PGV-1 (0.437±0.002 µM) and PGV-1+BSA (0.631±0.002 µM), highlighting the potent inhibitory effect of PGV-1+BSA+Lac on HLF cell proliferation. These findings suggest that PGV-1+BSA+Lac complexes hold promise as potential candidates for targeted PGV-1 delivery in HCC therap
Effect of Ethanol Percentage on Phytochemical Constituent, Antioxidant Activity, and Dermatological Potential of Cayratia trifolia (L.) Domin
Get PDFThe present investigation evaluated four different solvent compositions (water, 50% ethanol, 70% ethanol, and pure ethanol) for their relative capacity to extract, total phenolic (TP), total flavonoid (TF) components, antioxidant activities, and dermatological potential of leaves of Cayratia trifolia (L.) Domin. The TP and TF of extracts were measured using the Folin–Ciocalteau and AlCl3, respectively. Antioxidant activity was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP). Meanwhile, in vitro dermatological potential, tyrosinase, and elastase inhibitory are by the colorimetric method. The extract obtained by pure ethanol presented the most potent antioxidant activity. DPPH and FRAP IC50 values were 16.60±0.62 µg/mL and 27.53±0.69 µg/mL, respectively. The same extract also exhibited the highest TP (3.82±0.15 mg GAE/g DW) and TF (3.23±0.09 mg QE/g DW). Our finding additionally suggested that pure ethanol provides the highest extraction yield. However, 70% ethanol extract was a good source of tyrosinase (IC50, 60.49±7.73 µg/mL) and elastase inhibitor (IC50, 45.49±0.37 µg/mL). Overall, the experimental results revealed that C. trifolia has significant antioxidant and inhibitory action on skin-related tyrosinase and elastase, indicating that they might be used as bioactive metabolites in cosmetic and medicinal formulations to combat skin drooping and hyperpigmentation