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Stevia rebaudiana Bertoni is a perennial shrub from Paraguay that is nowadays widely cultivated, since it is increasingly being utilized as a sugar substitute in various foodstuffs due to its sweetness and minimal caloric content. These properties of the plant’s derivatives have spurred research on their biological activities revealing a multitude of benefits to human health, including antidiabetic, anticariogenic, antioxidant, hypotensive, antihypertensive, antimicrobial, anti-inflammatory and antitumor actions. To our knowledge, no recent reviews have surveyed and reported published work solely on the latter. Consequently, our main objective was to present a concise, literature-based review of the biological actions of stevia derivatives in various tumor types, as studied in in vitro and in vivo models of the disease. With global cancer estimates suggesting a 47% increase in cancer cases by 2040 compared to 2020, the data reviewed in this article should provide a better insight into Stevia rebaudiana and its products as a means of cancer prevention and therapy within the context of a healthy diet.

Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.

Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer–Emmett–Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of ORI@MOF-5 was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h. ORI@MOF-5 had significant cytotoxicity (IC50:22.99 μg/mL) and apoptosis effect on HepG2 cells. ORI@MOF-5 is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material.

Coffee is one of the most important beverages in the world and is produced from Coffea spp. beans. Diterpenes with ent-kaurane backbones have been described in this genus, and substances such as cafestol and kahweol have been widely investigated, along with their derivatives and biological properties. Other coffee ent-kaurane diterpenoids have been reported with new perspectives on their biological activities. The aim of this review is to update the chemical diversity of ent-kaurane diterpenoids in green and roasted coffee, detailing each new compound and reporting its biological potential. A systematic review was performed using the bibliographic databases (SciFinder, Web of Science, ScienceDirect) and specific keywords such as “coffea diterpenes”, “coffee diterpenes”, “coffee ent-kaurane diterpenes” and “coffee diterpenoids”. Only articles related to the isolation of coffee ent-kaurane compounds were considered. A total of 146 compounds were related to Coffea spp. since the first report in 1932. Different chemical skeletons were observed, and these compounds were grouped as furan-type, oxidation-type, rearrangement-type, lacton-type, and lactam-type, among others. In general, the new coffee diterpenoids showed potential as antidiabetic, antidiapogenic, α-glucosidade inhibition, antiplatelet activity, and Cav.3 inhibitors agents, revealing the possibilities for the design, discovery, and development of new drugs.

Diets high in sugar are recognized as a serious health problem, and there is a drive to reduce their consumption. Steviol glycosides are natural zero-calorie sweeteners, but the most desirable ones are biosynthesized with low yields. UGT76G1 catalyzes the β (1–3) addition of glucose to steviol glycosides, which gives them the preferred taste. UGT76G1 is able to transfer glucose to multiple steviol substrates yet remains highly specific in the glycosidic linkage it creates. Here, we report multiple complex structures of the enzyme combined with biochemical data, which reveal that the enzyme utilizes hydrophobic interactions for substrate recognition. The lack of a strict three-dimensional recognition arrangement, typical of hydrogen bonds, permits two different orientations for β (1–3) sugar addition. The use of hydrophobic recognition is unusual in a regio- and stereo-specific catalysis. Harnessing such non-specific hydrophobic interactions could have wide applications in the synthesis of complex glycoconjugates. UGT76G1 is an UDP-glucose dependent glycosyltransferase and a component of the biosynthesis pathway for the natural sugar substitute steviol glycoside. Here, the authors present substrate bound crystal structures of UGT76G1 and provide insights into substrate recognition and catalysis by the enzyme.

ent -Kaurane diterpenoids ( ent -KTs) represent a structurally diverse class of natural products renowned for their antitumor and anti-inflammatory bioactivities. The C-14 hydroxyl modification is crucial for enhancing their potency; however, introducing this functional group remains a considerable challenge. Here, we present a computational heme-guided site-specific (CHS) strategy to identify three bacterial P450s (CYP260A1, CYP105N1, and CYP154C5) for C-14 hydroxylation. Further computationally guided enzyme engineering and redox partner screening identify the CYP260A1 L162V variant paired with CamA/CamB, achieving a 52-fold increase in production titer and a yield of 84.2 mg/L of (14 R ,16 R )- ent -kauran-14,16-diol ( 2 ) in Escherichia coli . Substrate scope test reveals functional groups affecting reactivity. Structure-activity relationship studies demonstrate the synergistic effect between the C-14 hydroxyl and C15–C16 Michael acceptor, resulting in a potent derivative ( 27 ) with strong cytotoxicity (IC 50 HCT116  = 1.4 μM). This study demonstrates a framework combining CHS-guided P450 discovery and computational enzyme engineering to advance ent -KT modifications. C-14 hydroxyl group is critical for the function of ent -kaurane diterpenoids ( ent -KTs). Here, the authors report discovery and engineering of bacterial P450s for C-14 hydroxylation in ent -KTs.

Three novel ent-kaurane diterpenes, namely sigesbeckin A–C (1–3), in conjunction with eight previously identified analogues (4–11), were isolated from Sigesbeckia orientalis. Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 μg/mL. Moreover, compounds 3, 5, and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance.

Oridonin, a diterpenoid natural product commonly used in East Asian herbal medicine, is garnering increased attention in the biomedical community due to its extensive biological activities that include antitumor, anti-inflammatory, antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the past decade, significant progress has been made in structure activity relationship and mechanism of action studies of oridonin for the treatment of cancer and other diseases. This review provides a brief summary on oridonin and its analogs in cancer drug discovery and antiinflammation and highlights its emerging therapeutic potential in neuroprotection applications.

Oridonin (ORI), an ent-kaurene tetracyclic diterpenoid compound, is isolated from Chinese herb Rabdosia rubescens with various biological and pharmacological activities including anti-tumor, anti-microbial and anti-inflammatory effects. However, the clinical application of ORI is limited due to its low solubility and poor bioavailability. In order to overcome these shortcomings, many strategies have been explored such as structural modification, new dosage form, etc. This review provides a detailed discussion on the research progress to increase the solubility and bioavailability of ORI.