Paul Anthony Keller

1. Mankind has been dealing with the life-threatening Plasmodial fever, with the current global mortality rate ranging from 0.3% to 2.2%. Severe malaria cases in tropical regions can reach between ...

Reactions of N , N ′‐dimethylindigo with dichlorocarbene or rhodium carbenoids have been investigated leading to the one‐pot production of new, complex heterocyclic derivatives. One of these arises from an overall ring interconversion process with ring expansion to afford a novel eight‐membered ring‐fused benz[6,7][1,5]oxazocino[3,2‐ b ]indol‐13‐one derivative. Alternatively, an overall ring construction process gives rise to an unprecedented spirocyclic 2 H ,4 H ‐spiro[furo[3,2‐ b ]indole‐3,2′‐indoline] system. A number of products with an embedded 6 H ‐pyrido[1,2‐ a :3,4‐ b ′]diindole core from reaction with a rhodium malonyl ester carbenoid intermediate are also reported, plus some other carbenoid‐derived products. A solvent dependence is apparent with these reactions. Reaction path differences are also seen using N ‐methylindigo or the parent indigo as the substrate and possible mechanisms are proposed.

The tropical islands of Indonesia house the second largest biodiversity in the world. For generations, indigenous communities have relied on medicinal plants to treat various ailments, including diabetes. However, no comprehensive systematic review has been conducted to consolidate research progress in this area. This review aims to investigate and summarize the current research landscape on antidiabetic medicinal plants in Indonesia. Data collection, collation and analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant publications on the antidiabetic evaluation of Indonesian medicinal plants were retrieved from leading scientific databases, including Scifinder® and Garuda , yielding a total of 108 eligible articles. Several notable compound screening studies identified bioactive phytochemicals with significant antidiabetic potential, such as quinine as a SIRT1 activator, prunetin as an aldose reductase inhibitor, gallic acid as a pancreatic α-amylase (PPA) inhibitor, oleanolic acid as a PTP1B inhibitor, and 3,4,5-tri- O -caffeoylquinic acid methyl ester as an α-glucosidase inhibitor. Additionally, clinical investigations and community-based trials reported significant blood glucose-lowering effects from botanical extracts including Piper crocatum , Moringa oleifera , and Curcuma xanthorrhiza in diabetic patients. Recognizing the therapeutic potential of indigenous botanicals, the Indonesian government has intensified its support for the development of scientifically standardized herbal medicines aimed at diabetes treatment, positioning them as part of the country’s integrated healthcare system. Graphical abstract

The base-enabled reaction of buta-2,3-dien-1-yl methanesulfonate with the readily available and cheap dye indigo resulted in the convenient one-pot synthesis of benzoindolonaphthyridinedione and benzoazepinopyridoindolediones, with the latter representing two novel heterocyclic scaffolds. Despite the low yields, the allenylic alkylation of indigo significantly contributes to the new chemistry of this compound, providing new mechanistic insights and reactivity boundaries.

Tools for the rapid and comprehensive characterisation of photoinitiated polymerisation are required to expedite the development of next-generation photoinitiators. For many current workflows, the time consuming synthesis of photoinitiators, in moderate to large scale, impedes progress. This study demonstrates that online photoreactor mass spectrometry facilitates rapid screening of photoinitiated polymerisation on a small scale (ca. 1–5 mg). This is demonstrated by photolysis and polymerisation efficiency investigations of nine synthesised monoacylphosphine oxides (MAPOs) compared to a commercial MAPO (2,4,6-trimethylbenzoyl)diphenylphosphine oxide, (TPO)). All MAPOs undergo photolysis at 395 nm, except for two N(Me)₂ MAPOs despite their large absorption cross-sections. This highlights how absorptivity alone is an inadequate measure of photoinitiator performance. Additionally, seemingly subtle substitutions structural differences in the synthesised MAPOs result in drastic changes to the measured polymerisation efficiency. Further analysis attributes this to oxygen inhibition in the initial propagation steps and this demonstrates the advantages of online mass spectrometry to rapidly characterise photoinitiated chemistry.

Purpose: Lichens are well-known as a source of pharmacologically active compounds. This includes anticancer compounds which have biomass constraints including using traditional techniques of lichen bioprospecting. This current study reports the use of cutting-edge metabolomics and a computational approach to discover anticancer biomarkers from Indonesian lichens. Methods: Seven lichen crude extracts were evaluated against cervical cell lines HeLa using a MTT assay and secondary metabolites were profiled and recorded via a GCMS protocol. A multivariate analysis OPLSDA was employed to determine anticancer biomarker of the lichens. A structure-based computational study against the HeLa cancer cell related protein targets (BCL-2 (4MAN), AKT-1 (4GV1), MCL-1 (5FDO), and BRAF (5VAM)) was used to determine the most potent biomarker. Results: The MTT assessment indicated the seven lichens possessed strong, medium and weak cytotoxicity. Multivariate analysis showed an OPLS-DA score plot with distinct separation among the strong, medium and weak cytotoxic groups. The biplot OPLS-DA and GC-MS analysis proposed 13 compounds of Parmelia caroliniana and 12 compounds of Physcia cf. millegrana as anticancer biomarker candidates. Docking experiments revealed 6-amino-3,4,7-triphenylpyrido[2',3':4,5]thieno[2,3-c]pyridazine 4 from P. caroliniana to possess the highest binding affinity against BCL-2 (4MAN), AKT-1 (4GV1), MCL-1 (5FDO), and BRAF (5VAM) proteins with affinity energy values of -10.0, -11.6, -10.4, -12.6, respectively. Conclusion: The study successfully revealed compound 4 as the anticancer biomarker against HeLa cell cancer of P. caroliniana in which can be further explored through in vitro and in vivo studies. Further, the metabolomic protocol established can be adapted as a tool for biomarker discoveries from other medicinal plants.

Background: The Indonesian health care system comprises both modern and traditional medical systems; while they are not integrated, they have co-existed for decades. Traditional medical treatments continue to enjoy popularity nationwide, especially for people living in rural areas. Methods: We interviewed the traditional healers of the Tengger community (the last Hindu society in Java Island – Indonesia) and botanically identified their medicinal plants. The cross-sectional surveys were conducted based on an unstructured ethnopharmacology interview. Use Value (UV), Family Use Value (FUV), Infomart consensus factor (ICF) and Use-reports were derived as primary data. Results: Nineteen dukuns were identified and interviewed. The dukun (local healer) practiced both spiritual and physical medication (using medicinal plants and animals). There were 41 medicinal plants from 23 different families used for treating 17 ailments. The study revealed that although Tengger culture evolved from the Southeast Asian dominant Hindu Kingdom - Majapahit, only less than half of the species identified were contained in the PROSEA and Ayurvedic databases. Apium graveolens L., Causonis clematidea (F.Muell.) Jackes, Drymocallis arguta (Pursh) Rydb., Elaeocarpus longifolius Blume, Garcinia mangostana L., Rubus allegheniensis Porter, Tagetes tenuifolia Cav. were the most cited species. The scientific approach revealed the uses of A. gravelolens. G. mangostana, R. allegheniensis and T. tenuifolia. Conclusions: These findings revealed the medicinal potential of ethnopharmacology in the medicinal plants of Tengger however several medicinal plants required further scientific investigation. Keywords: Ethnopharmacology, Indonesia, Hinduism, Tengger, Medicinal plants

Natural occurring peroxides are interesting bioprospecting targets due to their molecular structural diversity and the wide range of pharmacological activities. In this systematic review, a total of 123 peroxide compounds were analysed from 99 published papers with the compounds distributed in 31 plants, 18 animals and 41 microorganisms living in land and water ecosystems. The peroxide moiety exists as both cyclic and acyclic entities and can include 1,2‐dioxolanes, 1,2‐dioxane rings and common secondary metabolites with a peroxo group. These peroxides possessed diverse bioactivities including anticancer, antimalarial, antimicrobial, anti‐inflammatory, neuroprotective, adipogenic suppressor, antituberculosis, anti‐melanogenic and anti‐coagulant agents. Biosynthetic pathways and mechanisms of most endoperoxides have not been well established. Method development in peroxide detection has been a challenging task requiring multidisciplinary investigation and exploration on peroxy‐containing secondary metabolites are necessary.