Drug resistant tuberculosis has threatened all the advances that have been made in TB control at the global stage in the last few decades. DNA gyrase enzymes are an excellent target for antibacterial drug discovery as they are involved in essential functions like DNA replication. Here we report, a successful application of high throughput virtual screening (HTVS) to identify an inhibitor of Mycobacterium DNA gyrase targeting the wild type and the most prevalent three double mutants of quinolone resistant DNA gyrase namely A90V+D94G, A74S+D94G and A90V+S91P.
Although the antimalarial agent artemisinin itself is not active against tuberculosis, conjugation to a mycobacterial-specific siderophore (microbial iron chelator) analogue induces significant and selective antituberculosis activity, including activity against multi- and extensively drug-resistant strains of Mycobacterium tuberculosis. The conjugate also retains potent antimalarial activity.
Many plants are used in Ayurveda for the treatment of tuberculosis. Our aim was to examine if these plants possess any specific molecule that inhibits Mycobacterium tuberculosis. One of them, Kaempferia galanga, yielded an anti-TB molecule, ethyl p-methoxycinnamate (EPMC). By resazurin microtitre assay (REMA), EPMC was shown to inhibit M. tuberculosis H37Ra, H37Rv, drug susceptible and multidrug resistant (MDR) clinical isolates (MIC 0.242-0.485mM). No cross resistance was observed to any standard anti-TB drugs in the MDR strains. The compound did not inhibit any prototype bacteria tested.
The crude extract of an Alaskan ethnobotanical plant, Oplopanax horridus, was subjected to counter-current chromatography (CCC), and the selected active regions were evaluated for their synergistic effects with an in vitro model of anti-tubercular efficacy. CCC as a support-free high-resolution separation method was employed to preclude potential irreversible absorption to a solid stationary phase. The microplate Alamar blue assay and the isobole method were used to measure the biological activity and eliminate dose-response dependent errors, respectively.
Following chemotaxonomic evidence, the PE and CHCl(3) extracts of the roots of the botanical Angelica sinensis (Oliv.) Diels (Dang Gui) were investigated for in vitro anti-TB activity, in parallel to studying their serotonergic and GABAergic potential. The activities were confirmed to overlap chemically with the neurotropic active principles present in medium lipophilic fractions.
Green tea, a product of the dried leaves of Camellia sinensis, is the most widely consumed beverage in the world. The polyphenolic compounds from green tea (PGT) possess antiinflammatory properties. We investigated whether PGT can afford protection against autoimmune arthritis and also examined the immunological basis of this effect using the rat adjuvant arthritis (AA) model of human rheumatoid arthritis (RA).
INTRODUCTION: Autoimmune inflammation is a characteristic feature of rheumatoid arthritis (RA) and other autoimmune diseases. In the natural course of human autoimmune diseases, it is rather difficult to pinpoint the precise timing of the initial event that triggers the cascade of pathogenic events that later culminate into clinically overt disease. Therefore, it is a challenge to examine the early preclinical events in these disorders. Animal models are an invaluable resource in this regard.
International Journal of Immunopathology and Pharmacology
Rheumatoid arthritis (RA) is a debilitating autoimmune disease of global prevalence and the disease process primarily targets the synovial joints. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. Celastrus has been used in China for centuries for the treatment of rheumatic diseases. Furthermore, we previously reported that ethanol extract of Celastrus aculeatus Merr. (Celastrus) attenuates adjuvant-induced arthritis (AA) in rats.
The majority of bioactive principles in a complex matrix such as natural products and botanical medicines are secondary rather than primary metabolites. In addition to being chemically diverse, the bioactivity of an ethnobotanical can comprise from one to several bioactive compounds, present in a complex mixture. Conventional discovery efforts utilize bioassay-guided fractionation (BGF) to isolate individual active compounds. When applied to complex natural products, BGF is often challenged by an apparent loss of activity during fractionation, resulting in weakly active isolated compounds.
The natural product engelhardione is an underexplored chemotype for developing novel treatments for bacterial infections; we therefore explored this natural product scaffold for chemical diversification and structure-activity relationship studies. Macrocyclic engelhardione and structural regioisomers were synthesized using a series of aldol condensations and selective hydrogenations to generate the 1,7-diarylheptan-3-one derivatives, followed by microwave-assisted intramolecular Ullmann coupling to afford a series of macrocyclic diaryl ether analogs.