Antibacterial and Anti-inflammatory Activity of Extracts and Major Constituents Derived from Stachytarpheta indica Linn. Leaves and Their Potential Implications for Wound Healing.

Wounds of various types continue to have a severe socioeconomic impact on the cost of health care. Globally, there has been increased interest surrounding the identification of bioactive compounds that promote or modulate the wound healing process. Stachytarpheta indica Linn. is traditionally used to heal wounds and relieve inflammation; however, the theorised pharmacological properties have not yet been scientifically validated. In this study, dried and ground plant leaves were extracted with water and methanol, which were then subjected to various analyses. The antimicrobial activity of the plant extracts and isolated compounds was determined using well diffusion assays, while the minimum inhibitory concentrations were determined with a colorimetric assay. Morphological changes of human keratinocytes in response to plant extracts were observed with differential interference contrast microscope imaging. Cell viability, proliferation, and migratory effects post-treatment with the plant extracts were also evaluated via colorimetric cytotoxicity assays and a real-time cell analyser protocol. Anti-inflammatory effects of plant extracts and isolated compounds were evaluated by flow cytometry and cyclooxygenase and lipoxygenase enzyme inhibition assays. Three active compounds, i.e. ipolamiide, verbascoside and iso-verbascoside, were isolated from S. indica leaves. Verbascoside demonstrated broad-range antibacterial activity and imposed strong inhibition at 9.77 µg/mL against Staphylococci spp. S. indica extracts (0.1-0.2 mg/mL) were shown to improve human keratinocyte proliferation up to 60% and induce morphological changes by producing cytoplasmic projections at concentrations higher than 0.4 mg/mL. Plant extracts (6.25-100 µg/mL) and individual compounds (3.125-50 µg/mL) elicited strong anti-inflammatory effects by suppressing the expression of interleukin-8 and inhibiting cyclooxygenase-1 and 5-lipoxygenase enzymes. Collectively, these results indicate that plant extracts and isolated compounds derived from S. indica have the potential to inhibit bacterial growth, promote tissue regeneration and reduce inflammation, hence, potentially providing the basis for a novel therapeutic for the treatment of wounds.

Antibacterial Potential of Extracts and Phytoconstituents Isolated from Syncarpia hillii Leaves In Vitro.

(1) Background: Rapidly increasing antibiotic resistance is one of the greatest threats to global health, affecting individuals regardless of age. Medicinal plants are widely used in traditional medicine to prevent and attenuate infectious conditions with minimal adverse effects. However, only a few have been phytochemically investigated for their medicinal properties and subsequent biological activities. Syncarpia hillii, a plant traditionally used by Indigenous Australians to treat sores, wounds, and skin infections, is no exception. (2) Methods: Primary extracts obtained from mature S. hillii leaves were evaluated for their antibacterial potential against 19 bacterial strains. The methanol extract was subjected to compound isolation and identification due to its preliminary bactericidal efficacy. (3) Results: Staphylococcal species were the most susceptible bacterial strain with a MIC value of 0.63 mg/mL to the S. hillii methanol extract. Quercetin-3-O-ß-D-glucuronide and shikimic acid isolated from S. hillii methanol leaf extracts exhibited enhanced antibacterial effects against the tested bacteria with quercetin-3-O-ß-D-glucuronide eliciting a MIC value of 0.78 µg/mL against E. faecalis. (4) Conclusions: S. hillii leaves are comprised of bioactive compounds that are bactericidal against several Gram-positive and Gram-negative bacteria.

Recent update on anti-dengue drug discovery.

Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014-2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.

Isolation of thuridillins D-F, diterpene metabolites from the Australian sacoglossan mollusk Thuridilla splendens; relative configuration of the epoxylactone ring.

This first chemical study of the sacoglossan mollusk Thuridilla splendens from Mooloolaba, South East Queensland, has resulted in the isolation of three new metabolites, thuridillins D-F (1-3), and one known metabolite, thuridillin A (4). Thuridillin D (1) was isolated by conventional flash chromatography on silica gel, while a mixture of thuridillins E (2) and F (3) was obtained by PTLC on AgNO(3)-impregnated silica gel. Thuridillins D-F were determined to be structurally related to thuridillin B (5); 1 possessed a hydroxy group at C-11, and 2 and 3 were Δ(10,11)- and Δ(11,12)-isomers, respectively. HSQC-HECADE NMR data, together with conformational analysis, NOESY experiments, and (1)H-(1)H coupling studies enabled assignment of the individual relative configurations of the epoxylactone, the 2,5-diacetoxy-2,5-dihydrofuran, and cyclohexyl moieties within thuridillin D (1).

A versatile synthetic approach toward diversity libraries using monosaccharide scaffolds.

The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build on 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied on glucose and allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations on a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics.

Alkaloids with human delta-opioid receptor binding affinity from the Australian rainforest tree Peripentadenia mearsii.

Three new pyrrolidine alkaloids, peripentonine A-C ( 2- 4), one known pyrrolidine alkaloid, peripentadenine ( 1), and one novel indolizidine alkaloid, mearsamine ( 5), were isolated from the leaves of Peripentadenia mearsii and their structures determined by 1D and 2D NMR spectroscopy. Peripentonines A ( 2) and B ( 3) were isolated as a 1:1 mixture of inseparable diastereomers. Mearsamine ( 5) contains a novel tricyclic ring system. Peripentadenine and peripentonines A/B and C showed receptor binding affinity for the human delta-opioid receptor with IC 50 values of 11.4, 69.2, and 30.9 microM, respectively. Mearsamine did not bind to the delta-opioid receptor.

Flavonoids as opioid receptor ligands: identification and preliminary structure-activity relationships.

Flavonoids have been recognized as the active ingredients of many medicinal plant extracts due to interactions with proteins via phenolic groups and low toxicity. Here, we report the investigation of the flavonoid core as a potential new scaffold for the development of opioid receptor ligands. Biological results suggest that stereochemistry of the C2 and C3 positions is important for antagonist activity and selectivity. Our results also suggest that the actions of Hypericum perforatum may be mediated in part by opioid receptors.

Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues.

Further modification of salvinorin A (1a), the major active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study that oxadiazole 11a and salvidivin A (12a), a photooxygenation product of 1a, have been identified as the first neoclerodane diterpenes with kappa antagonist activity. This indicates that additional structural modifications of 1a may lead to analogues with higher potency and utility as drug abuse medications.

Indolizidine alkaloids with delta-opioid receptor binding affinity from the leaves of Elaeocarpus fuscoides.

In the first chemical investigation of the Papua New Guinean plant Elaeocarpus fuscoides, one new indolizidine alkaloid, elaeocarpenine (1), and three known alkaloids, isoelaeocarpicine (2), isoelaeocarpine (3), and elaeocarpine (4), were isolated from the leaves. Their structures were determined by 1D and 2D NMR spectroscopy. Since treatment of elaeocarpenine (1) with ammonia produced a 1:1 mixture of the diastereomers 3 and 4, we propose that elaeocarpenine (1) is the biogenetic precursor of isoelaeocarpine (3) and elaeocarpine (4). Compounds 1-4 demonstrated binding affinity for the human delta-opioid receptor with IC50 values of 2.7, 35.1, 13.6, and 86.4 microM, respectively.

Habbemines A and B, pyrrolidine alkaloids with human delta-opioid receptor binding affinity from the leaves of Elaeocarpus habbemensis.

The first phytochemical investigation of the Papua New Guinean plant Elaeocarpus habbemensis resulted in the isolation of two new pyrrolidine alkaloids, habbemines A (2) and B (3), as a 1:1 mixture of inseparable diastereomers. The structures of these compounds and their relative configurations were determined by spectroscopic means. An equimolar mixture of habbemines A and B showed human delta-opioid receptor binding affinity with an IC50 of 32.1 microM.

Grandisines C-G, indolizidine alkaloids from the Australian rainforest tree Elaeocarpus grandis.

Five new indolizidine alkaloids, grandisines C, D, E, F, and G (4-8), and one known indolizidine alkaloid, (-)-isoelaeocarpiline (3), were isolated from the leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR spectroscopy. Grandisine C (4) is isomeric with the known compound rudrakine (1). The absolute configuration of grandisine D (5) was deduced by its conversion to (-)-isoelaeocarpiline. Grandisine E (6) contains a novel tetracyclic ring system. Grandisine F (7) is the 14-amino analogue of grandisine C. Grandisine G (8) contains the novel combination of a piperidine attached to an indolizidine. Grandisines C, D, F, and G and (-)-isoelaeocarpiline showed receptor binding affinity for the human delta-opioid receptor with IC(50) values of 14.6, 1.65, 1.55, 75.4, and 9.9 microM, respectively.