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 rare flavone 5,3′‐dihydroxy‐3,6,7,8,4′‐pentamethoxyflavone (PMF) has been isolated from several plant species, and its cytotoxic activity has been reported against many types of cancer cells. In this study, PMF was purified from Glycomis ovoidea collected in Vietnam, and its antiproliferative effects and underlying mechanism of action were investigated against MCF‐7 cells. PMF inhibited growth in MCF‐7 > MCF‐10A > MDA‐MB‐231 cells after 72 hr treatment, with IC50 values of 1.5, 1.9, and 8.6 μg/ml, respectively. Further experiments conducted with this compound in MCF‐7 cells, showed the loss of mitochondrial membrane potential, reactive oxygen species overproduction, upregulation of BAX, cytochrome c, caspase‐3 and PARP‐1 and down‐regulation of BCL‐2 proteins as well as an increase in caspase‐3/‐7 activity, suggesting induction of the apoptotic intrinsic pathway. Furthermore, PMF increased cell cycle arrest in the G1 phase, which correlated with increments in the p53 and p21 levels. Additionally, MCF‐7 cell migration was inhibited, which could be related to NF‐κB p65 downregulation. Finally, PMF did not show toxicity in vivo in a zebrafish (Danio rerio) model. In conclusion, PMF induces cell death in MCF‐7 cells through regulation of the BCL‐2 protein family and may be proposed as a lead as a potential alternative for breast cancer therapy.

The bioassay-guided fractionation of the aril of M. fragrans (mace spice) yielded five phenolic compounds, one new acyclic bis phenylpropanoid (1) and four previously known phenolic compounds: compounds (1) (S) 1-(3, 4, 5-trimethoxyphenyl)-2-(3-methoxy-5-(prop-1-yl) phenyl)-propan-1-ol, (2) benzenemethanol; α-[1-[2,6-dimethoxy-4-(2-propen-1-yl)phenoxy]ethyl]-3,4-dimethoxy-1-acetate, (3) odoratisol A, phenol, 4-[(2S, 3S)-2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-propenyl-2-benzofuranyl]-2,6-dimethoxy, (4) 1,3-benzodioxate-5-methanol,α-[1-[2,6-dimethoxy-4-(2-propenyl)phenoxy]ethyl]-acetate, (5) licarin C; benzofuran, 2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-yl-2-(3,4,5-trimethoxyphenyl). A NMR tube Mosher ester reaction was used in an approach to characterize and determine the assignment of the absolute configuration of the new isolated chiral alcohol (1). The PARP-1 inhibitory activity was evaluated for compound (1) (IC50 = 3.04 μM), compound (2) (IC50 = 0.001 μM), compound (4) (IC50 = 22.07 μM) and compound (5) (IC50 = 3.11 μM). Furthermore, the isolated secondary metabolites were tested for NF-κB and K-Ras inhibitory activities. When tested in the p65 assay, compounds (2) and (4) displayed potent NF-κB inhibition, (IC50 = 1.5 nM and 3.4 nM, respectively).

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In biological systems, conformational changes and allosteric modulation play pivotal roles in regulating biological functions, such as the dynamic change of protein molecules, in response to binding or interacting with other factors such as pH, voltage, salt, light, or ligand. RNA can be manipulated and tuned with a level of simplicity that is characteristic of DNA or polymers, while displaying versatility in structure, diversity in function, and adaptability in a configuration similar to proteins. In the past, the work on the investigation of conformational change mainly focused on protein. The induced-fit and conformational capture in RNA have also been explored, such as in the study of riboswitches. Herein, we report the engineering of three-dimensional RNA nanocubes and demonstrated the operation and regulation for its configuration. We demonstrate the operation of reconfigurable RNA nanocubes whose shapes change precisely and reversibly in response to a specific trigger strand. The shape, size, and conformation can be regulated precisely and reversibly in response to the specific triggering signals. The shape and conformational conversion were observed by cryo-EM and gel electrophoresis, respectively. Harnessing the size, shape, conformation, and self-assembly capabilities of the RNA nanocube can provide a new potential use of this technology as nanocarriers for the treatment of various diseases.

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