Hilwan Yuda Teruna

Candida infections remain difficult to treat because of antifungal resistance, toxicity, and suboptimal pharmacokinetics. This study comparatively evaluated fourteen structurally diverse flavonoids against Candida albicans , Candida glabrata , and Candida krusei to identify structure–activity, mechanistic, and early selectivity relationships rather than to rediscover previously reported activities of individual flavonoids. Antifungal activity was assessed by minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and time‐kill assays. Mechanistic evaluation included concentration‐dependent ergosterol depletion and a lanosterol 14α‐demethylase (CYP51)‐associated sterol readout, supported by validated molecular docking, pharmacophore modelling, molecular dynamics, and density functional theory calculations. Brine shrimp lethality, cytotoxicity in HepG2, HK‐2, and Vero cells, and in silico ADME/toxicity predictions provided preliminary selectivity information. Diosmin ( 3 ) and rutin ( 4 ) showed the strongest activity against C. albicans (MIC = 12.5 µM). Rutin ( 4 ) produced the strongest CYP51‐associated response (82.27%–84.75%), while diosmin ( 3 ) and rutin ( 4 ) showed docking scores of −12.15 and −11.38 kcal/mol, respectively. Rutin ( 4 ) also showed CC ₅₀ values of 500.65–800.63 µM. Overall, integrated cross‐assay analysis identified diosmin and rutin as the most consistent flavonoid leads.

This study utilized in vitro and in silico methods to assess the antifungal efficacy of synthesized pyrazoline derivatives (4a–e) against Candida species. The compounds were produced by a one-pot process and structurally analyzed using spectroscopic methods. The antifungal efficacy was evaluated against C. albicans, C. glabrata, and C. krusei using minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) assays. Among the derivatives, compound 4e exhibited potent antifungal action, displaying MIC values similar to ketoconazole. Molecular docking and pharmacophore modeling have shown that 4e interacts efficiently with critical residues of lanosterol 14α-demethylase (CYP51). The density functional theory (DFT) study indicated advantageous electrical characteristics, while molecular dynamics simulations validated the structural stability of the 4e–CYP51 complex, evidenced by low RMSD and RMSF values, along with an MM/GBSA binding energy comparable to that of ketoconazole. A robust association between binding energy and MIC substantiates the predictive use of computational data. The results suggest that compound 4e replicates the binding characteristics of ketoconazole and may be a viable candidate for antifungal medication development. This integrative strategy reinforces the justification for additional optimization and preclinical assessment of pyrazoline-based antifungal drugs aimed at CYP51.

Context: Helminthostachys zeylanica (L.) Hook., is a plant that has been used traditionally in Asia as a medicine. Its foliage is both utilized medicinally and consumed as a vegetable, whereas the rhizomes have historically been employed to treat a variety of conditions, including infectious diseases. Aims: To elucidate the phytochemical profile of H. zeylanica and assess its antibacterial potential through untargeted metabolomic analysis. Methods: Various parts of the plant were extracted using the maceration technique, and this was followed by evaluating the antibacterial activity using the Kirby-Bauer disc diffusion method. Then, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. Phytochemical analysis was performed using LC-HRMS. Multivariate analyses, including PCA and PLS-DA, were used to explore the variations in metabolite profiles and their association with antibacterial activity. Results: The results showed that the H. zeylanica extracts had moderate antibacterial activity, particularly against certain Gram-positive bacteria, though their efficacy was generally lower when compared to the standard antibiotic chloramphenicol. Metabolomic profiling revealed distinct metabolic signatures for each plant part, thereby emphasizing the unique phytochemical environments. Furthermore, our findings suggest that H. zeylanica contains bioactive compounds with selective antibacterial properties. However, its overall effectiveness, particularly against Gram-negative bacteria, is limited when compared to conventional antibiotics. Conclusions: This study not only contributes to the pharmacological understanding of H. zeylanica, but it also emphasizes the importance of comprehensive metabolomic analysis in determining the therapeutic potential of medicinal plants.

Considering the escalating resistance to conventional antifungal medications, it is critical to identify novel compounds that can efficiently counteract this challenge. The purpose of this research was to elucidate the fungicidal properties of secondary metabolites derived from Arcangelisia flava, with a specific focus on their efficacy against Candida species. This study utilized a combination approach comprising laboratory simulations and experiments to discern and evaluate the biologically active constituents present in the dichloromethane extract of A. flava. The in vitro experiments demonstrated that compounds 1 (palmatine) and 2 (fibraurin) exhibited antifungal properties. The compounds exhibited minimum inhibitory concentrations (MICs) ranging from 15.62 to 62.5 µg/mL against Candida sp. Moreover, compound 1 demonstrated a minimum fungicidal concentration (MFC) of 62.5 µg/mL against Candida glabrata and C. krusei. In contrast, compound 2 exhibited an MFC of 125 µg/mL against both Candida species. Based on a molecular docking study, it was shown that compounds 1 and 2 have a binding free energy of −6.6377 and −6.7075 kcal/mol, respectively, which indicates a strong affinity and specificity for fungal enzymatic targets. This study utilized pharmacophore modeling and Density Functional Theory (DFT) simulations to better understand the interaction dynamics and structural properties crucial for antifungal activity. The findings underscore the potential of secondary metabolites derived from A. flava to act as a foundation for creating novel and highly efficient antifungal treatments, specifically targeting fungal diseases resistant to existing treatment methods. Thus, the results regarding these compounds can provide references for the next stage in antifungal drug design. Further investigation is necessary to thoroughly evaluate these natural substances’ clinical feasibility and safety characteristics, which show great potential as antifungal agents.

Background: The need for new antibacterials to combat resistance is still constrained by the availability of antibacterials that are safe to use. Diterpene quinone-derived compounds are proven to have antibacterial activity. However, their mechanism of action is unknown. Objective: This study aims to determine the mechanism of antibacterial action of a diterpene quinone (6O7AR) on Staphylococcus aureus through in vitro and in silico assays. Method: MIC tests were performed using microdilution, and MBC determinations were carried out on MHA media. In vitro assays were conducted using membrane permeabilizing with Tris, Triton X-100, and ATPase-inhibiting agents with NaN3. Docking was performed on 2XCT proteins in S. aureus bacteria using AutoDock Vina. Result: The MIC and MBC results of 6O7AR were 300 μM and 2400 μM, respectively. The in vitro assay result suggested that the antimicrobial activities of 6O7AR were associated with the inhibition of ATPase function and disrupting membrane function. The docking results showed that the compound possessed good interactions with the 2XCT proteins of S. aureus. Conclusion: 6O7AR exhibited good antibacterial activity. Based on in vitro and in silico assays, the mechanism of action of this compound is related to the disruption of bacterial membrane function, and it has the potential to inhibit the ATPase enzyme and the S. aureus gyrase.

Pinocembrin (PCB), a flavonoid known for its anti‐inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti‐inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2S)‐PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines. This particular compound was isolated from Goniothalamus macrophyllus (Annonaceae), a native plant of Indonesia. This plant has been used traditionally as an herbal medicine to alleviate inflammation. (2S)‐PCB was isolated from the stem bark of G. macrophyllus by defatting with n‐hexane followed by maceration with methanol. Purification was performed using several chromatographic techniques. The absolute configuration was determined using electronic circular dichroism (ECD) spectroscopy. This compound was then tested for its inhibitory activity on prostaglandin E₂ (PGE₂) and subjected to docking simulations. The results indicated that (2S)‐PCB significantly suppressed the production of PGE₂ induced by LPS in both RAW 264.7 and U937 cell lines. The docking simulations revealed that (2S)‐PCB reduced PGE₂ levels by suppressing mitogen‐activated protein kinase (MAPK) activation through inhibiting p38 and extracellular signal‐regulated kinases (ERK). These findings suggest that the compound may prevent worsening of septic shock caused by bacterial infection.

Background: Medang lendir (Litsea glutinosa), a member of the Lauraceae family, is typically found in the Kampar Regency area of Riau Province, Indonesia. This plant is frequently used in traditional medicine to treat rheumatism, diarrhea, and dysentery. Objective: To evaluate the antioxidant activities of L. glutinosa stem bark extracts. Method: L. glutinosa stem bark was macerated in methanol to obtain methanol extract, followed by partitioning with ethyl acetate to obtain ethyl acetate extract. The antioxidant activities of these extracts were determined using the NO radical scavenging and the DPPH radical scavenging methods. The Folin-Ciocalteu method was also used in this study to determine total phenolic content (TPC). Result: The antioxidant activities of ethyl acetate and methanol extracts of L. glutinosa stem bark against NO radicals resulted in a small percentage of inhibition (%I < 0). Meanwhile, for DPPH radical scavenging, the antioxidant activity of the ethyl acetate extract (IC₅₀ = 222.03 ug/mL) was greater than the methanol extract (IC₅₀ = 232.81 ug/mL), and the TPC value of the ethyl acetate extract (23.88 mgGAE/g) was greater than the methanol extract (23.16 mgGAE/g). Conclusion: These results show that the antioxidant activity based on scavenging DPPH radicals for both extracts was active; however, it was inactive on NO radicals. The ethyl acetate extract possessed a higher TPC value compared to the methanol extract.

Background: Pyrrosia lanceolata (L.) farw. is one of the Polypodiaceae species that is commonly used as a traditional medicinal plant.  Objective: The purpose of this study was to determine the antioxidant and toxic levels in the extracts of the species. Method: The aerial portion of the specie was extracted with methanol, followed by a liquid-liquid extraction with n-hexane, dichloromethane, and ethyl acetate. DPPH radicals and the brine shrimp lethality test, , were used to assess its antioxidant activity and toxicity. Result: The n-hexane extract exhibited no activity with IC₅₀ values exceeding 500 μg/mL, whereas the ethyl acetate extract exhibited a high level of antioxidant activity with an IC₅₀ value of 12.08±0.27 μg/mL. Moreover, when tested against Artemia salina leach, the toxicological level of the extracts was greater than 1000 μg/mL. Conclusion: These findings lay the groundwork for further investigation into the process of isolating and evaluating the biological activity of secondary metabolites that were discovered in the extract.

Background: A coffee parasite, Loranthus ferrugineus, is a type of parasitic plant that is widely used as a medicinal plant. It has many activities, including as an antioxidant agent. Objective: This study is to determine the antioxidant activity in the twig extracts of L. ferrugineus. Method: The twigs of L. ferrugineus were collected from Pekanbaru, Riau Province, Indonesia. Extraction was carried out by maceration of the dry twigs using methanol, and then liquid-liquid extraction was carried out to obtain ethyl acetate and methanol fractions. The antioxidant activity test was carried out using the radical DPPH and NO free radical scavenging methods by calculating the IC₅₀ values, and the total phenolic content (TPC) was measured. Result: The antioxidant activity assay of the DPPH method on ethyl acetate and methanol extracts revealed IC₅₀ values of 20.85 µg/mL and 18.83 µg/mL, respectively. Meanwhile, the NO free radical method on ethyl acetate and methanol extracts showed IC₅₀ values of 78.52 µg/mL and greater than 1000 µg/mL. The total phenolic content of the ethyl acetate extract was 26.78 mgGAE/gram, while it was 24.85 mgGAE/gram in the methanol extract. Conclusion: The ethyl acetate and methanol extracts could inhibit free radicals from DPPH, which was classified as very strong antioxidant sources. Meanwhile, the inhibition of the extracts against the NO free radical was very weak.

Background: Pyrazolopyridines are heterocyclic compounds with nitrogen atoms in the ring, and they have been used as one of the important pharmacophores in drug design. Pyrazole derivatives have been synthesised and applied in the pharmaceutical industry as active drugs. The recent commercial success of pyrazole COX-2 inhibitors has brought even more attention to the significance of this heterocyclic ring in medicinal chemistry. Objective: This study aimed to synthesise new compounds as anti-inflammatory candidates from the pyrazolopyridine group. Method: Synthesis was carried out using the Claisen-Schmidt reaction through condensation of substituted benzaldehyde and 4-piperidone to produce mono-ketone curcumin analogues, which were then cyclised with phenylhydrazine. The results of the synthesis were characterised using FT-IR, 1H-NMR, and MS. Docking analysis was performed on the 3LN1 protein with MOE 2021.0901. Furthermore, an in vivo anti-inflammatory test was applied using a plethysmometer. Results: The synthesis results obtained two pyrazolopyridine compounds, and the docking results showed that both of these synthesised compounds could interact with the COX-2 receptor binding site. Conclusion: Compound 2 demonstrated good anti-inflammatory activities. This strategy is in the preliminary stages of identifying novel substances that may be used as anti-inflammatory agents in the future.