ABSTRACT
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.
Subject(s)
Leukemia, Myeloid, Acute , Triterpenes , Animals , Mice , Apoptosis , Cell Line , Cell Line, Tumor , fms-Like Tyrosine Kinase 3/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Mutation , Protein Kinase Inhibitors/pharmacology , Triterpenes/pharmacologyABSTRACT
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.
Subject(s)
Dental Caries , Piper , Plants, Medicinal , Anti-Bacterial Agents , Biofilms , Chlorhexidine/pharmacology , Dental Caries/drug therapy , Humans , Phytochemicals/analysis , Phytochemicals/pharmacology , Piper/chemistry , Plant Leaves/chemistry , Streptococcus mutansABSTRACT
Three new pentacyclic triterpenes, trivially named sandkoetjapic acids A-C (1-3), have been isolated from the leaves extract of Sandoricum koetjape, along with the known triterpenes 3-oxo-olean-12-en-29-oic (4), bryonolic (5), and bryononic (6) acids. The structures of the new triterpenes were determined mainly by NMR spectroscopic and mass spectroscopic data. The isolation of these pentacyclic triterpenes in the plant's leaves is for the first time. Preliminary biological evaluation of 1-6 was done against eight receptor tyrosine kinases (RTKs), including EGFR, HER2, HER4 (epidermal growth factor receptor), IGF1R, InsR (insulin receptor), KDR (kinase insert domain receptor), and PDGFRα/-ß (platelet-derived growth factor receptor), and their inhibitory properties against ß-lactamase. The results showed that none of them were active both as the inhibitors of these RTKs and ß-lactamase.
Subject(s)
Meliaceae , Triterpenes , Meliaceae/chemistry , Molecular Structure , Pentacyclic Triterpenes/analysis , Plant Extracts/analysis , Plant Extracts/pharmacology , Plant Leaves/chemistry , Triterpenes/chemistry , beta-Lactamases/analysisABSTRACT
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.
