Antifungal Constituents of Piper crocatum and Their Activities as Ergosterol Biosynthesis Inhibitors Discovered via In Silico Study Using ADMET and Drug-Likeness Analysis.

Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constituents from P. crocatum and evaluate their activities as ergosterol biosynthesis inhibitors via an in silico study of ADMET and drug-likeness analysis. Two new active compounds 1 and 2 and a known compound 3 were isolated, and their structures were determined using spectroscopic methods, while their bioactivities were evaluated via in vitro and in silico studies, respectively. Antifungal compound 3 was the most active compared to 1 and 2 with zone inhibition values of 14.5, 11.9, and 13.0 mm, respectively, at a concentration of 10% w/v, together with MIC/MFC at 0.31/1.2% w/v. Further in silico study demonstrated that compound 3 had a stronger ΔG than the positive control and compounds 1 and 2 with -11.14, -12.78, -12.00, and -6.89 Kcal/mol against ERG1, ERG2, ERG11, and ERG24, respectively, and also that 3 had the best Ki with 6.8 × 10-3, 4 × 10-4, 1.6 × 10-3, and 8.88 µM. On the other hand, an ADMET analysis of 1-3 met five parameters, while 1 had one violation of Ro5. Based on the research data, the promising antifungal constituents of P. crocatum allow P. crocatum to be proposed as a new antifungal candidate to treat and cure infections due to C. albicans.

Effectiveness of Bioactive Compound as Antibacterial and Anti-Quorum Sensing Agent from Myrmecodia pendans: An In Silico Study.

BACKGROUND: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that Myrmecodia pendans (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. This study aims to investigate and predict the action mode of antibacterial compounds with specific proteins by following the molecular docking approach. METHODS: butein (1), biflavonoid (2), 3″-methoxyepicatechin-3-O-epicatechin (3), 2-dodecyl-4-hydroxylbenzaldehyde (4), 2-dodecyl-4-hydroxylbenzaldehyde (5), pomolic acid (6), betulin (7), and sitosterol-(6'-O-tridecanoil)-3-O-ß-D-glucopyranoside (8) from M. pendans act as the ligand. Antibiotics or substrates in each protein were used as a positive control. To screen the bioactivity of compounds, ligands were analyzed by Prediction of Activity Spectra for Substances (PASS) program. They were docked with 12 proteins by AutoDock Vina in the PyRx 0.8 software application. Those proteins are penicillin-binding protein (PBP), MurB, Sortase A (SrtA), deoxyribonucleic acid (DNA) gyrase, ribonucleic acid (RNA) polymerase, ribosomal protein, Cytolysin M (ClyM), FsrB, gelatinase binding-activating pheromone (GBAP), and PgrX retrieved from UniProt. The docking results were analyzed by the ProteinsPlus and Discovery Studio software applications. RESULTS: most compounds have Pa value over 0.5 against proteins in the cell wall. In nearly all proteins, biflavonoid (2) has the strongest binding affinity. However, compound 2 binds only three residues, so that 2 is the non-competitive inhibitor. CONCLUSION: compound 2 can be a lead compound for an antibacterial agent in each pathway.

Phytochemical Analysis and Anti-Biofilm Potential That Cause Dental Caries from Black Cumin Seeds (Nigella sativa Linn.).

The oral cavity is an excellent place for various microorganisms to grow. Spectrococcus mutans and Spectrococcus sanguinis are Gram-negative bacteria found in the oral cavity as pioneer biofilm formers on the tooth surface that cause caries. Caries treatment has been done with antibiotics and therapeutics, but the resistance level of S. mutans and S. sanguinis bacteria necessitates the exploration of new drug compounds. Black cumin (Nigella sativa Linn.) is known to contain secondary metabolites that have antioxidant, antibacterial, anti-biofilm, anti-inflammatory and antifungal activities. The purpose of this review article is to present data on the potential of Nigella sativa Linn seeds as anti-biofilm. This article will discuss biofilm-forming bacteria, the resistance mechanism of antibiotics, the bioactivity of N. sativa extracts and seed isolates together with the Structure Activity Relationship (SAR) review of N. sativa compound isolates. We collected data from reliable references that will illustrate the potential of N. sativa seeds as anti-biofilm drug.

Natural Cycloartane Triterpenoids from Corypha utan Lamk. with Anticancer Activity towards P388 Cell Lines and their Predicted Interaction with FLT3.

BACKGROUND: Cancer is the second leading cause of death in the world. Leukemia is a type of cancer that accounts for 31.5% of all cancers in children under the age of 15 in industrialized countries and 15.7% in developing countries. The inhibition of FMS-like tyrosine kinase 3 (FLT3) is a suitable approach for acute myeloid leukemia (AML) therapy as it is overexpressed in AML. AIM AND OBJECTIVE: This study intends to explore the natural constituents from the bark of Corypha utan Lamk., and assess their cytotoxicity on murine leukemia cell lines (P388) in addition to predicting their interaction with FLT3 as a studied target by computational methods. METHODS: Compounds 1 and 2 were isolated from Corypha utan Lamk using the stepwise radial chromatography method. These compounds were assessed for their cytotoxicity against Artemia salina using the BSLT and P388 cells and the MTT assay. The docking simulation was employed to predict the possible interaction between triterpenoid and FLT3. RESULTS: Isolation from the bark of C. utan Lamk. generated two triterpenoids, cycloartanol (1) and cycloartanone (2). Based on the in vitro and in silico studies, both compounds were found to have anticancer activity. The evaluation of cytotoxicity from this study reveals that cycloartanol (1) and cycloartanone (2) could inhibit P388 cell growth (IC50 value at 102.6 and 110.0 µg/mL, respectively). The binding energy of cycloartanone was -9.94 Kcal/mol with a Ki value of 0.051 µM, while the binding energy and Ki value of cycloartanol (1) were found to be 8.76 Kcal/mol and 0.38 µM, respectively. These compounds also demonstrate a stable interaction by forming hydrogen bonds with FLT3. CONCLUSION: Cycloartanol (1) and cycloartanone (2) exhibit potency as anticancer agents by inhibiting P388 cells in vitro and the FLT3 gene in silico.

Mode action prediction of catechin from Uncaria gambir Roxb. against UDP-N-acetylenolpyruvyl-glucosamine reductase (MurB enzyme) of Streptococcus mutans: In silico study.

The prevalence of oral health problems in the global population is still high, especially dental caries, which is considered a multifactorial disease involving the role of bacteria, namely Streptococcus mutans. Gram-positive bacteria metabolize carbohydrates and sugars and convert them into lactic acid, causing dental caries. The peptidoglycan (PG) layer at the outer surface of the bacteria acts as protection. MurB enzyme is known for its contribution to PG biosynthesis. Gambir (Uncaria gambir Roxb.) is famous for many efficacies. Previous studies show that catechin from herb plants such as U. gambir has antibacterial activity. This study aimed to evaluate and predict the antibacterial activity of catechin from U. gambir against the MurB enzyme, which contributes to forming the bacteria PG, with an in silico approach. The structure of the MurB enzyme was collected from UniProt, and the ligands (catechin and chlorhexidine) structures were obtained from PubChem. The AutoDock software was used to dock both ligand and MurB enzyme visualized using PyMOL and analyzed using BIOVIA. The results showed that catechin has a binding affinity of more than - 7 kcal/mol against the MurB enzyme, and chlorhexidine has a higher binding affinity than catechin. Both catechin and chlorhexidine have similar amino acids attachment by hydrogen bonds. The results showed that catechin has competitive antibacterial activity against chlorhexidine in inhibiting the MurB enzyme.

Potential of MurA Enzyme and GBAP in Fsr Quorum Sensing System as Antibacterial Drugs Target: In vitro and In silico Study of Antibacterial Compounds from Myrmecodia pendans.

BACKGROUND: Increasing the resistance issue has become the reason for the development of new antibacterial in crucial condition. Many ways are tracked to determine the most effective antibacterial agent. Some proteins that are a key role in bacteria metabolism are targeted, including MurA in cell wall biosynthesis and gelatinase biosynthesis-activating pheromone (GBAP) in Fsr Quorum Sensing (QS) system. OBJECTIVE: The objective of this research is the analysis of compounds 1-4 from M. pendans as antibacterial and anti-QS activity trough protein inhibition by in silico study; focus on the structure-activity relationships, to appraise their role as an antibacterial and anti-QS agent in the molecular level. METHODS: Both activities of M. pendans compounds (1-4) were analyzed by in silico, compared to Fosfomycin, Ambuic acid, Quercetin, and Taxifolin as a standard. Chemical structures of M. pendans compounds were converted using an online program molview. The compounds were docked to MurA, GBAP, gelatinase and serine protease using Autodock Vina in Pyrx 0.8 followed PYMOL to visualization and proteis.plus program to analyze of the complex. RESULTS: All compounds from M. pendans bound on MurA, GBAP, gelatinase and serine protease except compound 2. This biflavonoid did not attach to MurA and serine protease yet is the favorable ligand for GBAP and gelatinase with the binding affinity of -6.9 and -9.4 Kcal/mol respectively. Meanwhile, for MurA and serine protease, compound 4 is the highest of bonding energy with values of -8.7 and -6.4 Kcal/mol before quercetin (MurA, -8.9 Kcal/mol) and taxifolin (serine protease, -6.6 Kcal/mol). CONCLUSION: Based on the data, biflavonoid acts better as anti-QS than an inhibitor of MurA enzyme while the others can be acted into both of them either the therapeutic agent of anti-QS or antibacterial agent of MurA inhibitor.

Antibacterial Flavonoids Against Oral Bacteria of Enterococcus Faecalis ATCC 29212 from Sarang Semut (Myrmecodia pendans) and Its Inhibitor Activity Against Enzyme MurA.

BACKGROUND: A significant number of antibiotics are known to inhibit peptidoglycan synthesis in the cross-linking stage, while the drug fosfomycin is the only one known to inhibit MurA. Escalated antibiotic resistance has had an impact on the efficacy of fosfomycin, thus demanding the discovery of suitable substitutes with improved potential for MurA inhibition. The aim of this work is to isolate antibacterial compounds from Sarang Semut (Myrmecodia pendans) and to evaluate their antibacterial activity against pathogenic oral bacteria of Enterococcus faecalis ATCC 29212 and inhibitory activity against MurA enzyme. METHODS: The antibacterial compounds from Sarang Semut were isolated by a bioactivity-guided separation method with various solvents and combination of column chromatography on normal and reverse phases. The compounds with concentrations of 1000 and 5000 ppm were assessed against E. faecalis ATCC 29212 by agar well diffusion method, with chlorhexidine and fosfomycin being used as positive controls. RESULTS: Two antibacterial compounds isolated from Sarang Semut were identified as two new flavonoids derivates of 1 (10 mg) and 2 (4 mg). Both compounds were tested for antibacterial activities against E. faecalis. MIC values of compounds 1 and 2 were 8.15 and 8.05 mm at 1000 ppm and 8.62 and 8.55 mm at 5000 ppm, respectively. MBC values were 156 and 625 ppm for 1 and 625 and 2500 ppm for 2, respectively. In an inhibitory murA enzyme activity assay, compounds 1 and 2 were shown to inhibit the enzyme activity by IC50 values of 21.7 and 151.3 ppm. CONCLUSION: The study demonstrated that ethyl acetate fraction of Sarang Semut contained antibacterial flavonoids as active constituents that showed activity against E. faecalis. These results showed the plant's potential in herbal medicine and the development of new antibacterial agent for pathogenic dental caries.