Sesquiterpene lactones are of considerable interest due to their potent bioactivities, including cancer cell cytotoxicity and antineoplastic efficacy in in vivo studies. Among these compounds, ...artesunate, dimethylaminoparthenolide, and L12ADT peptide prodrug, a derivative of thapsigargin, are being evaluated in the current cancer clinical or preclinical trials. Based on the structures of several antitumor sesquiterpene lactones, a number of analogues showing greater potency have been either isolated as natural products or partially synthesized, and some potential anticancer agents that have emerged from this group of lead compounds have been investigated extensively. The present review focuses on artemisinin, parthenolide, thapsigargin, and their naturally occurring or synthetic analogues showing potential anticancer activity. This provides an overview of the advances in the development of these types of sesquiterpene lactones as potential anticancer agents, including their structural characterization, synthesis and synthetic modification, and antitumor potential, with the mechanism of action and structure-activity relationships also discussed. It is hoped that this will be helpful in stimulating the further interest in developing sesquiterpene lactones and their derivatives as new anticancer agents.
Naturally occurring terpenoid lactones and their synthetic derivatives have attracted increasing interest for their promising antitumor activity and potential utilization in the discovery and design ...of new antitumor agents. In the present perspective article, selected plant-derived five-membered γ-lactones and six-membered δ-lactones that occur with terpenoid scaffolds are reviewed, with their structures, cancer cell line cytotoxicity and in vivo antitumor activity, structure–activity relationships, mechanism of action, and the potential for developing cancer chemotherapeutic agents discussed in each case. The compounds presented include artemisinin (ART, 1), parthenolide (PTL, 2), thapsigargin (TPG, 3), andrographolide (AGL, 4), ginkgolide B (GKL B, 5), jolkinolide B (JKL B, 6), nagilactone E (NGL E, 7), triptolide (TPL, 8), bruceantin (BRC, 9), dichapetalin A (DCT A, 10), and limonin (LMN, 11), and their naturally occurring analogues and synthetic derivatives. It is hoped that this contribution will be supportive of the future development of additional efficacious anticancer agents derived from natural products.
Covering: 2006 to 2013. Investigations on the chemistry and biology of rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species during the period 2006-2013 are ...reviewed. Included are new phytochemical studies of naturally occurring rocaglamide derivatives, an update on synthetic methods for cyclopentabbenzofurans, and a description of the recent biological evaluation and mechanism-of-action studies on compounds of this type.
Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery ...continues to provide new and important leads against various pharmacological targets including cancer, HIV/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether, galantamine, nitisinone, and tiotropium, or are currently involved in late-phase clinical trials. As part of our National Cooperative Drug Discovery Group (NCDDG) research project, numerous compounds from tropical rainforest plant species with potential anticancer activity have been identified. Our group has also isolated several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials, the selection and implementation of appropriate high-throughput screening bioassays, and the scale-up of active compounds.
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Cantharidin is a potent natural protein phosphatase monoterpene anhydride inhibitor secreted by several species of blister beetle, with its demethylated anhydride analogue, ...(S)-palasonin, occurring as a constituent of the higher plant Butea frondosa. Cantharidin shows both potent protein phosphatase inhibitory and cancer cell cytotoxic activities, but possible preclinical development of this anhydride has been limited thus far by its toxicity. Thus, several synthetic derivatives of cantharidin have been prepared, of which some compounds exhibit improved antitumor potential and may have use as lead compounds. In the present review, the potential antitumor activity, structure-activity relationships, and development of cantharidin-based anticancer drug conjugates are summarized, with protein phosphatase-related and other types of mechanisms of action discussed. Protein phosphatases play a key role in the tumor microenvironment, and thus described herein is also the potential for developing new tumor microenvironment-targeted cancer chemotherapeutic agents, based on cantharidin and its naturally occurring analogues and synthetic derivatives.
Higher plant constituents have afforded clinically available anticancer drugs. These include both chemically unmodified small molecules and their synthetic derivatives currently used or those in ...clinical trials as antineoplastic agents, and an updated summary is provided. In addition, botanical dietary supplements, exemplified by mangosteen and noni constituents, are also covered as potential cancer chemotherapeutic agents. Approaches to metabolite purification, rapid dereplication, and biological evaluation including analytical hyphenated techniques, molecular networking, and advanced cellular and animal models are discussed. Further, enhanced and targeted drug delivery systems for phytochemicals, including micelles, nanoparticles and antibody drug conjugates (ADCs) are described herein.
The development and progression of colorectal cancer (CRC) is closely related to gut microbiome. Here, the impact of lipopolysaccharide (LPS), one of the most prevalent products in the gut ...microbiome, on CRC immunotherapy is investigated. It is found that LPS is abundant in orthotopic CRC tissue and is associated with low responses to anti‐PD‐L1 mAb therapy, and clearance of Gram‐negative bacteria from the gut using polymyxin B (PmB) or blockade of Toll‐like receptor 4 using TAK‐242 will both relieve the immunosuppressive microenvironment and boost T‐cell infiltration into the CRC tumor. Further, an engineered LPS‐targeting fusion protein is designed and its coding sequence is loaded into a lipid–protamine–DNA (LPD) nanoparticle system for selective expression of LPS trap protein and blocking LPS inside the tumor, and this nanotrapping system significantly relieves the immunosuppressive microenvironment and boosts anti‐PD‐L1 mAb therapy against CRC tumors. This LPS trap system even attenuates CRC liver metastasis when applied, suggesting the importance of blocking LPS in the gut–liver axis. The strategy applied here may provide a useful new way for treating CRC as well as other epithelial cancers that interact with mucosa microbiome.
Nanotechnology‐based trapping of lipopolysaccharide, a prevalent product of gut microbiome, boosts checkpoint blockade immunotherapy against colorectal cancer (CRC) and attenuates liver metastasis. The strategy applied here may provide a useful new way for treating CRC as well as other epithelial cancers that interact with the mucosa microbiome.
Ethnobotanical studies have been of very great importance in recognizing plants that contain substances that modulate the heterodimer T1R2-T1R3 sweet taste receptor, inclusive of Stevia rebaudiana ...(Asteraceae) and Siraitia grosvenorii (Cucurbitaceae).
In addition to reviewing relevant ethnobotanical literature, inclusive of original field work conducted, the authors have provided a progress report on the ultimate regulatory acceptance of highly sweet ent-kaurane (steviol) diterpene glycosides from S. rebaudiana leaves (“stevia”) and cucurbitane triterpene glycosides (mogrosides) from the fruits of S. grosvenorii (popularly known as “monk fruit”). Despite their relatively high prices relative to that of sucrose, the steviol glycosides and mogrosides are of current great interest for further more extensive utilization on the market as sweet-tasting non-caloric food additives, due to increases in the rates of obesity and diabetes all over the world. Recent phytochemical work on the sweet principles of these two species is highlighted, including the important “next-generation” sweetener, rebaudioside M, from S. rebaudiana.
Initial observations on the ethnobotany of both S. rebaudiana and S. grosvenorii have proved crucial to indicating the presence of their sweet-tasting principles to the wider scientific community.
Ethnobotanical observations have been pivotal in enabling the discovery of many sweet-tasting plant constituents, with those of S. rebaudiana and S. grosvenorii both being examples. Extractives prepared from these species are now commercially used widely in the U.S. as additives for the sweetening of foods and beverages.
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