Isolation, Characterization, and Antiproliferative Activity of Terpenoids from the Tropical Plant .

The isolation, structure determination, and biological evaluation of constituents from the organic extract of Wahlert (Meliaceae) resulted in the isolation of 51 secondary metabolites, including 14 new terpenoids (six cycloartanes, four tirucallanes/euphanes, three limonoids, and a 7-keto sterol). Among the new compounds, is the first triterpenoid with a trioxaspiro[4.4]nonane side chain, while - are the first 17-γ-lactone tetranortriterpenoids with four oxygenated functional groups at C-1, -3, -6, and -7.

Unusual Vilasinin-Class Limonoids from .

Eight vilasinin-class limonoids, including the unusually chlorinated rubescins K-M (-), the 2,3-epoxylated rubescin N (), and rubescins O-R (-), were newly isolated from . The structures of the isolated compounds were determined through spectroscopic and spectrometric analyses, as well as ECD calculations. The natural occurrence of chlorinated limonoids - was confirmed by chemical methods and HPLC analysis of a roughly fractionated portion of the plant extract.

Caged Xanthones and Biphenyls Isolated from the Tropical Plant .

Four cytotoxic heptacyclic caged-xanthones [gambogefic acids B-E (-)], a cytotoxic hexacyclic caged-xanthone [garcilatelic acid ()], and four biphenyl derivatives [garcilatelibiphenyls A-D (-)] were newly isolated in a phytochemical study of a 50% MeOH/CHCl extract of (Clusiaceae). The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines including a vincristine-resistant line. The new caged-xanthones displayed potent activity with IC values from 0.

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.

Increasing evidence implicates the tumor microbiota as a factor that can influence cancer progression. In patients with colorectal cancer (CRC), we found that pre-resection antibiotics targeting anaerobic bacteria substantially improved disease-free survival by 25.5%.

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations.

HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat.

Antiproliferative Effect of N-Heterocyclo-Coumarin Derivatives against Multidrug-Resistant Cells.

Chemotherapy refers principally to the use of small molecules to treat cancer, and natural product derivatives have been main sources of clinically using anticancer drugs. While the coumarin skeleton does not inhibit cell growth, its derivatives are often active, and numerous coumarins have been examined for antiproliferative activity against human cancer cell lines. In this study, 16 novel coumarin derivatives (1, 1a-5a, 1b, 2b, 6b, 7b, 8-13) with attached N-heterocycles, including aminopyrrolidine, aminopiperidine, aminoazepane, and indoline, were prepared and ultimately esterified or amidated with alcohols or amines, respectively.

Palladium (II), platinum (II) and silver (I) complexes with oxazolines: Their synthesis, characterization, DFT calculation, molecular docking and antitumour effects.

Six new Pd(II), Pt(II) and Ag(I) complexes, (1);{Pd (L)]2CH}Cl} (2); Pt(L)(DMSO)Cl; 3; {PtL]CH}·PhCOO⋅11NO; 4; {[Pt(L)]CH}; the binuclear cyclometalated complex the polymer chain (5); {[PtL]CH}·NO}; and the polymeric silver species (6); Zn(L)·AgNO·CHCl were synthesized and thoroughly characterized using X-ray diffraction and spectroscopic techniques (L=(S,S)-1,4-i-PrOx]CH}Cl, L=Di(2,2-bis(4R-isopropyl-4,5-dihydro-oxazol-2-yl)acetonitrile) zinc (II) (B);L= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene (A); L= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene，L=1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)-benzene，L=Di(2,2-bis(4S-isopropyl-4,5-dihydrooxazol-2-yl)acetonitrile) zinc (II). Complexes 1-6 showed cytotoxic effects against human tumour cell lines, including a multidrug-resistant subline. Oxazoline and Pd complex 1 induced apoptosis in A549 cells.

Tigliane-Type Diterpene Esters from the Fruits of and Their Anti-HIV Activity.

Four new diterpene esters, shirakindicans A-D (-), along with eight related known diterpene esters (-), were isolated from the fruits of the Bangladeshi medicinal plant . The structures of - were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Shirakindican A () was assigned as a tigliane-type diterpene ester possessing an unusual 6β-hydroxy-1,7-dien-3-one structure, while shirakindican B () exhibits a tiglia-1,5-dien-3,7-dione structure.

Discovery of C-Diterpenoid Alkaloid Kobusine Derivatives Exhibiting Sub-G1 Inducing Activity.

Although many diterpenoid alkaloids have been evaluated recently for antiproliferative activity against human cancer cell lines, little data have been offered relating to the antiproliferative effects of hetisine-type C-diterpenoid alkaloids, such as kobusine (), likewise as their derivatives. A total of 43 novel diterpenoid alkaloid derivatives (, , , , , , , , , , , , , ) were prepared by C-11 and -15 esterification of . Antiproliferative effects of the natural parent compound () and all synthesized kobusine derivatives against human cancer cell lines, including a triple-negative breast cancer (TNBC) cell line as well as a P-glycoprotein overexpressing multidrug-resistant subline, were assessed.

Identification of Novel 4'--Demethyl-epipodophyllotoxin Derivatives as Antitumor Agents Targeting Topoisomerase II.

C4 variation of 4'--demethyl-epipodophyllotoxin (DMEP) is an effective approach to optimize the antitumor spectra of this compound class. Accordingly, two series of novel DMEP derivatives were synthesized, and as expected, the antitumor spectra of these derivatives varied with different C4 substituents. Notably, most compounds showed significant inhibition against the etoposide (2)-resistant KBvin cells.

MicroRNA-Mediated Mitochondrial Dysfunction Is Involved in the Anti-triple-Negative Breast Cancer Cell Activity of Phytosesquiterpene Lactones.

Emerging evidence suggests that modulating redox homeostasis through targeting mitochondrial functions may be a useful strategy for suppressing triple-negative breast cancer (TNBC) activities. However, whether there are specific microRNAs (miRNAs) involved in regulating oxidative stress-associated mitochondrial functions that can act as therapeutic targets to suppress TNBC activities remains unclear. Here, we aimed to identify the role of redox-associated miRNAs in TNBC and investigated their potential as therapeutic targets.

Bioactivity inspired C-diterpenoid alkaloids for overcoming multidrug-resistant cancer.

The pharmacological activities of C-diterpenoid alkaloids are related to their basic skeletons (e.g., aconitine-type or lycoctonine-type).

Biology of quinoline and quinazoline alkaloids.

Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted scientific and popular interest worldwide since the 19th century. More than 600 compounds have been isolated from nature to date. To build on our two prior reviews, we reexamined the promising molecules described in previous reports and provided updated literature on novel quinoline and quinazoline alkaloids isolated over the past 5 years.

Phyto-sesquiterpene lactones DET and DETD-35 induce ferroptosis in vemurafenib sensitive and resistant melanoma via GPX4 inhibition and metabolic reprogramming.

Acquired resistance to vemurafenib (PLX4032) is a thorny issue in BRAF mutant melanoma therapy. Ferroptotic programmed cell death is a potential strategy for combating therapy-resistant cancers. This study uncovers the adaptation and abnormal upregulation of PUFAs and bioactive oxylipin metabolism in PLX4032 resistant melanoma cells.

Molecular hybridization used to design and synthesize neo-tanshinlactone derivatives as PD-1/PD-L1 inhibitors.

Four series of molecular hybrids (37 final products) of neo-tanshinlactone, a natural product extracted from Salvia miltiorrhiza Bunge, and known PD-1/PD-L1 interaction inhibitors were prepared as possible chemotherapeutic agents against triple negative breast cancer. Screening using a homogenous time-resolved fluorescence method resulted in three lead compounds (MZ52 IC 74 ± 4 nM; MZ58 IC 134 ± 17 nM; MZ61 IC 225 ± 19 nM). With less T cell cytotoxicity and effects in activating CD8 T cells in a T cell proliferation assay and a functionality experiment, MZ58 was selected as the best candidate for animal experiments.

Lead Optimization: Synthesis and Biological Evaluation of PBT-1 Derivatives as Novel Antitumor Agents.

Phenanthrene-based tylophorine-1 (PBT-1) was identified previously as a lead compound in an anticancer drug discovery effort based on natural alkaloids. An expanded structural optimization using a new more efficient synthetic route provided 14 PBT-derivatives. Eleven compounds displayed obvious antiproliferative activities in cellular assays (GI 0.

Eleven new C-diterpenoid alkaloids from Delphinium elatum cv. Pacific Giant.

Diterpenoid alkaloids, the main components of plants of the genera Aconitum, Delphinium, and Garrya, are a group of natural products with notable chemical properties and biological activities. Several C-diterpenoid alkaloid components from Delphinium elatum cv. Pacific Giant, as well as their derivatives, exhibited cytotoxic activity against lung, prostate, cervical, and vincristine-resistant cervical cancer cell lines.

Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors.

The HIV-1 Capsid (CA) is considered as a promising target for the development of potent antiviral drugs, due to its multiple roles during the viral life cycle. Herein, we report the design, synthesis, and antiviral activity evaluation of series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors. Among them, 4-methoxy-N-methylaniline substituted phenylalanine (II-13c) and indolin-5-amine substituted phenylalanine (V-25i) displayed exceptional anti-HIV-1 activity with the EC value of 5.

LC-MS Identification, Isolation, and Structural Elucidation of Anti-HIV Tigliane Diterpenoids from .

Structurally diverse tigliane diterpenoids have drawn significant research interest for drug discovery over many decades. Using LC-MS-guided fractionation and separation, the first phytochemical investigation on led to the isolation of eight tiglianes (-), including two new compounds, wikstrocin D () and wikstrocin E (). The new structures were elucidated based on extensive physicochemical and spectroscopic analyses.

New phorbol ester derivatives as potent anti-HIV agents.

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines.

Identification of anti-HIV macrocyclic daphnane orthoesters from Wikstroemia ligustrina by LC-MS analysis and phytochemical investigation.

Macrocyclic daphnane orthoesters (MDOs) have attracted significant research interest for the drug discovery to cure HIV infection based on the "Shock and Kill" strategy. In the present study, the first chemical study on Wikstroemia ligustrina (Thymelaeaceae) was carried out by LC-MS analysis and phytochemical investigation. Nine daphnane diterpenoids (1-9) including seven MDOs were detected by LC-MS analysis.

Identification of 3, 4-disubstituted pyridine derivatives as novel CDK8 inhibitors.

Selective inhibition of cyclin-dependent kinase 8 (CDK8) has been recently regarded as a potential approach for cancer therapy. A series of novel CDK8 inhibitors with the pyridine core was identified via scaffold hopping from the known CDK8 inhibitor A-7. The new inhibitors were designed to improve the ligand efficiency so as to enhance drug-likeness.

Hyperdioxanes, dibenzo-1,4-dioxane derivatives from the roots of Hypericum ascyron.

Six dibenzo-1,4-dioxane derivatives (1-6) were isolated from the roots of a Hypericaceous plant Hypericum ascyron. Spectroscopic analyses revealed 2 and 4-6 to be new compounds. The partial racemic natures of 1-3 were concluded by chiral HPLC analyses, while 5 was confirmed to be a racemate.

Selectfluor-Enabled C(sp)-H Alkoxylation of 3-Methylfuranocoumarins.

A facile and metal-free method for the direct C(sp)-H bond alkoxylation of 3-methylfuranocoumarins with alcohols has been disclosed. Selectfluor enabled the (hetero)benzylic C-H etherification by tuning the reaction temperature and solvent. Various alcohols were compatible in this transformation with suitable yields.

Sesquiterpene Lactone Deoxyelephantopin Isolated from and Its Derivative DETD-35 Suppress BRAF Mutant Melanoma Lung Metastasis in Mice.

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5 BRAF mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5 melanoma growth in vitro and in a xenograft mouse model.