Unveiling the Anti-Cancer Potential of Onoceranoid Triterpenes from Lansium domesticum Corr. cv. kokosan: An In Silico Study against Estrogen Receptor Alpha.

Breast cancer is a significant global concern, with tamoxifen, the standard treatment, raising long-term safety issues due to side effects. In this study, we evaluated the potential of five onoceranoid triterpenes from Lansium domesticum Corr. cv. kokosan against estrogen receptor alpha (ERα) using in silico techniques. Utilizing molecular docking, Lipinski's rule of five, in silico ADMET, and molecular dynamics simulations, we assessed the potency of five onoceranoid triterpenes against ERα. Molecular docking indicated competitive binding energies for these triterpenes relative to the active form of tamoxifen (4OHT) and estradiol, an ERα native ligand. Three triterpenes met drug-likeness criteria with favorable ADMET profiles. Notably, 2 demonstrated superior binding affinity in molecular dynamics simulations, outperforming estradiol, closely followed by 3 and 4. Hierarchical clustering on principal components (HCPC) and the spatial distribution of contact surface area (CSA) analyses suggest that these triterpenes, especially 2, may act as antagonist ligands akin to 4OHT. These findings highlight the potential of onoceranoid triterpenes in treating ERα-related breast cancer.

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.

New Triterpenoids from Lansium domesticum Corr. cv kokossan and Their Cytotoxic Activity.

Lansium domesticum Corr. is a member of the Meliaceae family that is widely spread in tropical and subtropical region of Asia and America. Traditionally, the fruit of this plant has been consumed because of its sweet taste. However, the fruit peels and the seeds of this plant have been rarely utilized. The previous chemical investigation of this plant showed the presence of secondary metabolites with many biological activities, including cytotoxic triterpenoid. Triterpenoids is a class of secondary metabolites which contain thirty carbon atoms in the main skeleton. The high modification of this type of compound, including the ring opening, highly oxygenated carbons, and the degradation of its carbon chain to give the nor-triterpenoid structure, is responsible for its cytotoxic activity. In this paper, we isolated and elucidated the chemical structure of two new onoceranoid triterpenes, kokosanolides E (1) and F (2), from the fruit peels of L. domesticum Corr., along with a new tetranortriterpenoid, kokosanolide G (3), from the seeds of L. domesticum Corr. The structural determination of compounds 1-3 was undertaken through FTIR spectroscopic analysis, 1D and 2D NMR, mass spectrometry, as well as through a comparison of the chemical shifts of the partial structures of compounds 1-3 with the literature data. The cytotoxic properties of compounds 1-3 were tested against MCF-7 breast cancer cells using the MTT assay. Moderate activity was shown by compounds 1 and 3, with IC50 values of 45.90 and 18.41 µg/mL, respectively, while compound 2 showed no activity (IC50 168.20 µg/mL). For the onoceranoid-type triterpene, the high symmetrical structure of compound 1 is presumably the reason for its better cytotoxic activity compared with that of compound 2. Compound 3 showed moderate activity, mainly because of the presence of the furan ring, which, based on the literature, gives better cytotoxic activity in a tetranortriterpenoid-type structure. The findings of three new triterpenoid compounds from L. domesticum indicate the significant value of this plant as a source of new compounds.

Phytochemical Profile of Antibacterial Agents from Red Betel Leaf (Piper crocatum Ruiz and Pav) against Bacteria in Dental Caries.

Based on data from The Global Burden of Disease Study in 2016, dental and oral health problems, especially dental caries, are a disease experienced by almost half of the world's population (3.58 billion people). One of the main causes of dental caries is the pathogenesis of Streptococcus mutans. Prevention can be achieved by controlling S. mutans using an antibacterial agent. The most commonly used antibacterial for the treatment of dental caries is chlorhexidine. However, long-term use of chlorhexidine has been reported to cause resistance and some side effects. Therefore, the discovery of a natural antibacterial agent is an urgent need. A natural antibacterial agent that can be used are herbal medicines derived from medicinal plants. Piper crocatum Ruiz and Pav has the potential to be used as a natural antibacterial agent for treating dental and oral health problems. Several studies reported that the leaves of P. crocatum Ruiz and Pav contain secondary metabolites such as essential oils, flavonoids, alkaloids, terpenoids, tannins, and phenolic compounds that are active against S. mutans. This review summarizes some information about P. crocatum Ruiz and Pav, various isolation methods, bioactivity, S. mutans bacteria that cause dental caries, biofilm formation mechanism, antibacterial properties, and the antibacterial mechanism of secondary metabolites in P. crocatum Ruiz and Pav.

Current Research of Phytochemical, Medicinal and Non-Medicinal Uses of Uncaria gambir Roxb.: A Review.

Uncaria gambir Roxb. is a plant from Southeast Asia and is widely used as an alternative medicine with various applications. This plant has been widely used in traditional medicine. This paper aims to provide information on U. gambir, a summary of data on phytochemicals and on medical and nonmedical activities. Phytochemical studies reveal biologically active constituents such as flavonoids, phenolics, and alkaloids. Various studies have shown that extracts and compounds obtained from U. gambir have medical uses for their antioxidant, antibacterial, anti-helminthic, anticancer, antifungal, anti-inflammatory, anti-hyperglycemic, anti-hyperuricemic, anti-lipid peroxidation, antihyperlipidemic and other properties. In addition, this extract has other uses, such as adsorbent for dyes and metal ions, as well as corrosion inhibition. Thus, U. gambir, which is commonly used in traditional medicine, is a potential plant for many therapeutic applications and prospects for drug development as well as other applications such as adsorbent and corrosion inhibition.

A Review of Bioactive Compounds and Antioxidant Activity Properties of Piper Species.

Antioxidants are compounds that are able to inhibit the negative effects that come from free radicals. The phenomenon of imbalanced antioxidant production and the accumulation of free radicals in cells and tissues can cause oxidative stress. Excessive free radicals that enter the body cannot be warded off by endogenous antioxidant compounds so that the required antioxidant compounds can come from the outside, which helps in the performance of endogenous antioxidants. Antioxidants that come from outside consist of synthetic and natural antioxidants; however, synthetic antioxidants are not an option because they have toxic and carcinogenic effects. Therefore, the use of natural ingredients is an alternative method that is needed to create a new natural antioxidant compound. Piper species are being considered as possible medicinal plants for the development of new sources of antioxidants. Several studies have been carried out starting from the extract levels, fractions, and compounds of the Piper species, which showed good antioxidant activity. Currently, some of these plants are being used as ingredients in traditional medicines to treat allergies, toothaches, and coughs. This review examines the distribution, botanical data, pharmacology, especially antioxidant activity, and the compounds contained in five Piper species, namely Piper amalago L., Piper betle L., Piper hispidum Sw., Piper longum L., and Piper umbellatum L.

Ocimum Species: A Review on Chemical Constituents and Antibacterial Activity.

Infection by bacteria is one of the main problems in health. The use of commercial antibiotics is still one of the treatments to overcome these problems. However, high levels of consumption lead to antibiotic resistance. Several types of antibiotics have been reported to experience resistance. One solution that can be given is the use of natural antibacterial products. There have been many studies reporting the potential antibacterial activity of the Ocimum plant. Ocimum is known to be one of the medicinal plants that have been used traditionally by local people. This plant contains components of secondary metabolites such as phenolics, flavonoids, steroids, terpenoids, and alkaloids. Therefore, in this paper, we will discuss five types of Ocimum species, namely O. americanum, O. basilicum, O. gratissimum, O. campechianum, and O. sanctum. The five species are known to contain many chemical constituents and have good antibacterial activity against several pathogenic bacteria.

Antioxidant Properties and Structure-Antioxidant Activity Relationship of Allium Species Leaves.

Allium is a genus that is widely consumed and used as traditional medicine in several countries. This genus has two major species, namely cultivated species and wild species. Cultivated species consist of A. cepa L., A. sativum L., A. fistulosum L. and A. schoenoprasum L. and wild species consist of A. ursinum L., A. flavum L., A. scorodoprasum L., A. vineale L. and A. atroviolaceum Boiss. Several studies report that the Allium species contain secondary metabolites such as polyphenols, flavonoids and tannins and have bioactivity such as antioxidants, antibacterial, antifungal, anti-inflammatory, pancreatic α-amylase, glucoamylase enzyme inhibitors and antiplatelets. This review summarizes some information regarding the types of Allium species (ethnobotany and ethnopharmacology), the content of compounds of Allium species leaves with various isolation methods, bioactivities, antioxidant properties and the structure-antioxidant activity relationship (SAR) of Allium compounds.

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.

Bio-Mechanism of Catechin as Pheromone Signal Inhibitor: Prediction of Antibacterial Agent Action Mode by In Vitro and In Silico Study.

The utilization of medicinal plants has long been explored for the discovery of antibacterial agents and the most effective mechanisms or new targets that can prevent and control the spread of antibiotic resistance. One kind of bacterial cell wall inhibition is the inactivation of the MurA enzyme that contributes to the formation of peptidoglycan. Another approach is to interfere with the cell-cell communication of bacteria called the Quorum sensing (QS) system. The blocking of auto-inducer such as gelatinase biosynthesis-activating pheromone (GBAP) can also suppress the virulence factors of gelatinase and serine protease. This research, in particular, aims to analyze lead compounds as antibacterial and anti-QS agents from Gambir (Uncaria gambir Roxburgh) through protein inhibition by in silico study. Antibacterial agents were isolated by bioactivity-guided isolation using a combination of chromatographic methods, and their chemical structures were determined by spectroscopic analysis methods. The in vitro antibacterial activity was evaluated by disc diffusion methods to determine inhibitory values. Meanwhile, in the in silico analysis, the compound of Uncaria gambir was used as ligand and compared with fosfomycin, ambuic acid, quercetin, and taxifolin as the standard ligand. These ligands were attached to MurA, GBAP, gelatinase, and serine proteases using Autodock Vina in PyRx 0.8 followed by PYMOL for combining the ligand conformation and proteins. plus programs to explore the complex, and visualized by Discovery Studio 2020 Client program. The antibacterial agent was identified as catechin that showed inhibitory activity against Enterococcus faecalis ATCC 29212 with inhibition zones of 11.70 mm at 10%, together with MIC and MBC values of 0.63 and 1.25 µg/mL, respectively. In the in silico study, the molecular interaction of catechin with MurA, GBAP, and gelatinase proteins showed good binding energy compared with two positive controls, namely fosfomycin and ambuic acid. It is better to use catechin-MurA (-8.5 Kcal/mol) and catechin-gelatinase (-7.8 Kcal/mol), as they have binding energies which are not marginally different from quercetin and taxifolin. On the other hand, the binding energy of serine protease is lower than quercetin, taxifolin, and ambuic acid. Based on the data, catechin has potency as an antibacterial through the inhibition of GBAP proteins, gelatinase, and serine protease that play a role in the QS system. This is the first discovery of the potential of catechin as an alternative antibacterial agent with an effective mechanism to prevent and control oral disease affected by antibiotic resistance.

A terpenoid isolated from sarang semut (Myrmecodia pendans) bulb and its potential for the inhibition and eradication of Streptococcus mutans biofilm.

BACKGROUND: Dental caries remains a serious problem due to its detrimental effects on individual health and quality of life. The bulbs of Myrmecodia pendans (Merr & Perry), native plants of Papua, have been used as natural remedies for tumours, gout, diarrhoea, and fever. In this study, one of the active compounds of M. pendans was isolated, and its biological activity against the formation of Streptococcus mutans ATCC 25175 biofilm was tested. METHODS: M. pendans was extracted with ethyl acetate using a Soxhlet apparatus. The extract was then separated, and chromatographic purification provided the isolated compound. The structure of the active compound was then characterized using UV, IR, NMR, and MS spectrometry. The obtained compound was added to S. mutans biofilms to determine the MBIC and MBEC values. RESULTS: The compound isolated from M. pendans was determined to be a labdane diterpene derivative with the formula C31H50O3. The MBIC value of the terpenoid towards the S. mutans biofilms was 50 ppm, and the MBEC value for the 1 min induction time was 40%. CONCLUSION: The terpenoid extracted from M. pendans has the potential to be developed into an antibacterial agent particularly for preventing the formation of biofilms.

Potential antioxidant and antiradical agents from Allium ascalonicum: Superoxide dismutase and density functional theory in silico studies.

Antioxidants are compounds that can inhibit excessive free radical reactions in the body. Excessive free radicals can cause system imbalances in the body which can trigger oxidative stress and cause serious illness. The limitations of antioxidants in the body can be overcome by consuming safe natural additional antioxidants that can be obtained from natural products. Isolating compounds of Allium ascalonicum leaves as antioxidant and antiradical agents in inhibiting excessive free radicals by in vitro and in silico. The extracted compounds were purified by column chromatography. The compounds obtained were then characterized using ultraviolet, infrared, NMR, and mass spectrometry. Determination of antioxidant activity was carried out by in vitro using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the non-enzymatic superoxide dismutase (SOD) methods. The in silico study used the density functional theory (DFT) calculation method with global descriptive parameters (GDP), donor acceptor map (DAM), and frontier molecular orbitals (FMO) analysis. Three compounds have been isolated, of which compound 1 is a new compound. In the DPPH method, compound 1 has more strong antioxidant activity than others, as well as in the non-enzymatic SOD method. Whereas, in the DFT calculation shows that compound 1 has the best reactivity and stability between other compounds and was categorized as the best antiradical. Compound 1 has the highest antioxidant activity compared to the other compounds by in vitro both the DPPH and non-enzymatic SOD methods. In silico, compound 1 has the potential as the best antiradical.

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.

Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav.

The WHO Global Status Report on Oral Health 2022 reveals that oral diseases caused by infection with oral pathogenic microorganisms affect nearly 3.5 billion people worldwide. Oral health problems are caused by the presence of S. mutans, S. sanguinis, E. faecalis and C. albicans in the oral cavity. Synthetic anti-infective drugs have been widely used to treat oral infections, but have been reported to cause side effects and resistance. Various strategies have been implemented to overcome this problem. Synthetic anti-infective drugs have been widely used to treat oral infections, but they have been reported to cause side effects and resistance. Therefore, it is important to look for safe anti-infective alternatives. Ethnobotanical and ethnopharmacological studies suggest that Red Betel leaf (Piper crocatum Ruiz & Pav) could be a potential source of oral anti-infectives. This review aims to discuss the pathogenesis mechanism of several microorganisms that play an important role in causing health problems, the mechanism of action of synthetic oral anti-infective drugs in inhibiting microbial growth in the oral cavity, and the potential of red betel leaf (Piper crocatum Ruiz & Pav) as an herbal oral anti-infective drug. This study emphasises the importance of researching natural components as an alternative treatment for oral infections that is more effective and can meet global needs.

Potential Piperolactam A Isolated From Piper betle as Natural Inhibitors of Brucella Species Aminoacyl-tRNA Synthetase for Livestock Infections: In Silico Approach.

Brucellosis is an important global zoonosis caused by the bacterium Brucella sp. Brucellosis causes abortions, reproductive failure and reduced milk production, resulting in significant economic losses. Brucella species are reported to be resistant to antibiotics, which makes treatment difficult. The urgency of discovering new drug candidates to combat Brucella's infection necessitates the exploration of novel alternative agents with unique protein targets. Aminoacyl-tRNA synthetases (aaRSs), which have fundamental functions in translation, inhibit this process, stop protein synthesis and ultimately inhibit bacterial growth. The purpose of this study was to isolate piperolactam A compounds from the methanol extract of Piper betle leaves that have potential as antibacterials to inhibit the growth of Brucella sp. causing brucellosis in livestock and to analyse the mechanism of inhibitory activity of piperolactam A compounds against the aaRS enzyme through a molecular docking approach in silico. Piperolactam A was isolated from P. betle by column chromatography and characterized by UV, IR, 1D and 2D NMRs and MS, then tested for their inhibition mechanism against the enzymes threonyl-tRNA synthetase, leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase in silico. The result in silico test is that piperolactam A has the potential to inhibit LeuRS enzyme with the greater binding affinity.

Moringa oleifera: A Review of the Pharmacology, Chemical Constituents, and Application for Dental Health.

Moringa oleifera L., commonly known as Kelor in Indonesia and miracle tree in English, has a rich history of utilization for medicinal, nutritional, and water treatment purposes dating back to ancient times. The plant is renowned for its abundance of vitamins, minerals, and various chemical constituents, making it a valuable resource. Among its notable pharmacological properties are its effectiveness as an anti-diabetic, anti-diarrheal, anti-helmintic, anti-leishmanial, anti-fungal, anti-bacterial, anti-allergic, anti-cancer, anti-inflammatory, and anti-oxidant agent. In this comprehensive review, we delve into the extensive pharmacological applications and phytochemical constituents of M. oleifera and its application in dental health.

Potential of Syzygnium polyanthum as Natural Food Preservative: A Review.

Food preservation is one of the strategies taken to maintain the level of public health. Oxidation activity and microbial contamination are the primary causes of food spoilage. For health reasons, people prefer natural preservatives over synthetic ones. Syzygnium polyanthum is widely spread throughout Asia and is utilized as a spice by the community. S. polyanthum has been found to be rich in phenols, hydroquinones, tannins, and flavonoids, which are potential antioxidants and antimicrobial agents. Consequently, S. polyanthum presents a tremendous opportunity as a natural preservative. This paper reviews recent articles about S. polyanthum dating back to the year 2000. This review summarizes the findings of natural compounds presented in S. polyanthum and their functional properties as antioxidants, antimicrobial agents, and natural preservatives in various types of food.

Potential of 24-Propylcholestrol as Immunity Inducer against Infection of COVID-19 Virus: In Silico Study Immunomodulatory Drugs.

BACKGROUND: COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has infected millions of people and caused hundreds of thousands of deaths worldwide. However, until now no specific drug for SARS-CoV-2 infection has been found. This prompted many researchers to explore compounds as anti-SARS-CoV-2 candidates. One of the efforts to deal with the spread of the COVID-19 virus is to increase the body's immune system (immune). Medicinal plants are known to have the ability as immune-modulators, one of which is Betel leaf (Piper betle L.) which has good activity as antibacterial, antioxidant, and anti-viral with other pharmacological effects. An in silico approach in drug development was used to search for potential antiviral compounds as inhibitors of SARS-CoV-2 Mpro Protein, RBD, and Non-structural Protein (NSP15). OBJECTIVE: This study aimed to determine the potential of Betel leaf compounds as immunemodulators and good inhibitory pathways against COVID-19. METHODS: In this study, a potential screening of steroid class compounds, namely 24- propilcholesterol was carried out as an anti-SARS-CoV-2 candidate, using an in silico approach with molecular docking simulations for three receptors that play an important role in COVID-19, namely Mpro SARS-CoV-2, RBD SARS-CoV-2 and a non-structural protein (NSP15) and were compared with Azithromycin, Favipiravir and Ritonavir as positive controls. RESULTS: Based on the results of molecular docking simulations, compound from Betel leaf, 24- Propylcholesterol, showed high binding affinity values for spike glycoprotein RBD and nonstructural protein 15 (NSP15), namely -7.5 and -7.8 kcal/mol. Meanwhile, a native ligand of Mpro, inhibitor N3, has a higher binding affinity value than 24-propylcholesterol -7.4 kcal/mol. CONCLUSION: 24-Propylcholesterol compound predicted to have potential as an anti-SARS-CoV-2 compound. However, it is necessary to carry out in vitro and in vivo studies to determine the effectiveness of the compound as an anti-SARS-CoV-2.

Potential Nevadensin from Ocimum basilicum as Antibacterial Agent against Streptococcus mutans: In Vitro and In Silico Studies.

BACKGROUND: Streptococcus mutans is one of the bacteria that contributes to biofilm formation and causes dental caries. The inhibition of SrtA, gbpC, and Ag I/II is a promising target to be developed as an antibacterial. Ocimum basilicum is known to have antibacterial activity. AIM AND OBJECTIVE: The aim of this study is to evaluate the potential nevadensin as antibacterial against S. mutans. METHODS: Antibacterial analysis was carried out by disc diffusion and micro-dilution methods and the in-silico study was performed with ligand-protein docking. RESULTS: The result showed that the MIC and MBC values of nevadensin are 900 and 7200 µg/mL, respectively. The binding energy of nevadensin to SrtA, gbpC, and Ag I/II were -4.53, 8.37, -6.12 kcal/mol, respectively. CONCLUSION: Nevadensin shows moderate activity as an antibacterial against S. mutans. Meanwhile, in silico studies showed it has the same binding strength as chlorhexidine in inhibiting SrtA, whereas to gbpC and Ag I/II, it has a weaker binding affinity. Therefore, nevadensin has the potential as a natural antibacterial against S. mutans by inhibiting SrtA.

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.