Background: Canarium patentinerviumleaves are used by the local indigenous people of Malaysia for wound healing. The current study is undertaken to screen the comprehensive antibacterial activity of the leaves and barks extracts, fractions and isolated compounds from this plant. Bioassay guided fractionation was also undertaken to deeply evaluate the antibacterial activity of the water fraction of the leaves extract. This is to provide preliminary scientific evidence to the ethnopharmacology usage of this plant by investigating antibacterial properties of the plant and its isolated constituents.Methods: Bio-assay guided fractionation and subsequent isolation of compounds using open column chromatography. The antibacterial activity against gram positive and gram negative ATCC strain and resistant clinical strains were evaluated using microtiter broth dilution method to determine minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assay. The chemical structure of the isolated compounds from the water fraction of the ethanol extract of leaves was elucidated using Nuclear Magnetic Resonance (NMR).Results: The ethanol extract of the leaves and barks showed antimicrobial activity against all four ATCC and eight clinical isolates. The ethanol extract of the leaves and the corresponding water fraction had good activity against MRSAS. aureus.(MIC: 250 μg/ml) and had bactericidal effect on eight of the clinical strains (MSSA,MRSA, oxacillin-resistant CONS, oxacillin-sensitive CONS,Enterococcus faecalis,Klebsielaspecies, Kleb pneumoniaeESBL andCandida parapsilosis). Further phytochemical investigation of the water fraction of the crude ethanol extract of leaves afforded compound 7 (hyperin) and compound 8 (cynaroside) that had bactericidal activity against tested bacterial species (MIC 50 μg/ml and 100 μg/ml). The two compounds were isolated from this genus for the first time.Conclusions: These results may provide a rational support for the traditional use ofCanarium patentinerviumMiq. in infections and wound healing, since the antimicrobial compounds isolated were also present in the leaves extract.

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.

Antimicrobial resistance (AMR) occurs when microbes no longer respond to any pharmacological agents, rendering the conventional antimicrobial agents ineffective. AMR has been classified as one of the top 10 life-threatening global health problems needed multilevel attention and global cooperation to attain the Sustainable Development Goals (SDGs) according to the World Health Organization (WHO), making the discovery of a new and effective antimicrobial agent a priority. The recommended treatments for drug-resistant microbes are available but limited. Furthermore, the transformation of microbes over time increases the risk of developing drug resistance. Hence, plant metabolites such as terpenes, phenolic compounds and alkaloids are widely studied due to their antibacterial, antiviral, antifungal and antiparasitic effects. Plant-derived antimicrobials are preferred due to their desirable efficacy and safety profile. Plant metabolites work by targeting microbial cell membranes, interfering with the synthesis of microbial DNA/RNA/enzymes and disrupting quorum sensing and efflux pump expression. They also work synergistically with conventional antibiotics to enhance antimicrobial effects. Accordingly, this review aims to identify currently available pharmacological therapies against microbes and AMR, as well as to discuss the importance of plant and secondary metabolites as a possible solution for AMR together with their mechanisms of action. All the information was obtained from government databases, WHO websites, PubMed, Springer, Google Scholar and Science Direct. Based on the information obtained, AMR is regarded as a significant warning to global healthcare. Plant derivatives such as secondary metabolites may be considered as potential therapeutic targets to mitigate the non-ending AMR.

Bioassay guided fractionation of an ethanol extract of leaves ofCanarium patentinerviumMiq. (Burseraceae Kunth.) led to the isolation of scopoletin. The structure of this coumarin was elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D) and mass spectrometry. Scopoletin inhibited the enzymatic activity of 5-lipoxygenase and acetyl cholinesterase with an IC₅₀equal to1.76±0.01 μM and0.27±0.02 mM, respectively, and confronted oxidation in the ABTS, DPPH, FRAP, andβ-carotene bleaching assay with EC₅₀values equal to5.62±0.03 μM,0.19±0.01 mM,0.25±0.03 mM and0.65±0.07 mM, respectively. Given the aforementioned evidence, it is tempting to speculate that scopoletin represents an exciting scaffold from which to develop leads for treatment of neurodegenerative diseases.

The emergence of multidrug-resistant bacteria and fungi requires the development of antibiotics and antifungal agents. This review identified natural products isolated from Asian angiosperms with antibacterial and/or antifungal activities and analyzed their distribution, molecular weights, solubility, and modes of action. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1979 to 2022. One hundred and forty-one antibacterial and/or antifungal alkaloids were identified during this period, mainly from basal angiosperms. The most active alkaloids are mainly planar, amphiphilic, with a molecular mass between 200 and 400 g/mol, and a polar surface area of about 50 Ų, and target DNA and/or topoisomerase as well as the cytoplasmic membrane. 8-Acetylnorchelerythrine, cryptolepine, 8-hydroxydihydrochelerythrine, 6-methoxydihydrosanguinarine, 2′-nortiliacorinine, pendulamine A and B, rhetsisine, sampangine, tiliacorine, tryptanthrin, tylophorinine, vallesamine, and viroallosecurinine yielded MIC ≤ 1 µg/mL and are candidates for the development of lead molecules.

As the fourth most diagnosed cancer, cervical cancer (CC) is one of the major causes of cancer-related mortality affecting females globally, particularly when diagnosed at advanced stage. Discoveries of CC biomarkers pave the road to precision medicine for better patient outcomes. High throughput omics technologies, characterized by big data production further accelerate the process. To date, various CC biomarkers have been discovered through the advancement in technologies. Despite, very few have successfully translated into clinical practice due to the paucity of validation through large scale clinical studies. While vast amounts of data are generated by the omics technologies, challenges arise in identifying the clinically relevant data for translational research as analyses of single-level omics approaches rarely provide causal relations. Integrative multi-omics approaches across different levels of cellular function enable better comprehension of the fundamental biology of CC by highlighting the interrelationships of the involved biomolecules and their function, aiding in identification of novel integrated biomarker profile for precision medicine. Establishment of a worldwide Early Detection Research Network (EDRN) system helps accelerating the pace of biomarker translation. To fill the research gap, we review the recent research progress on CC biomarker development from the application of high throughput omics technologies with sections covering genomics, transcriptomics, proteomics, and metabolomics.