Site-dependent modulation of antitumor activity and fluorescence in thieno[3,2-]pyridin-5(4)-ones.

We report the design and synthesis of thieno[3,2-]pyridin-5(4)-one derivatives exhibiting site-dependent modulation of both antitumor activity and fluorescence, enabled by a regioselective BOP-promoted aza-[3 + 3] cycloaddition. The reaction proceeds between thiophen-3-amines and α,β-unsaturated carboxylic acids, followed by base-induced dehydrogenation. Mechanistic studies reveal that the head-to-tail aza-[3 + 3] annulation involves a -1,4 conjugate addition, leading to an intramolecular amide coupling.

Novel quinazoline-triazole-based -hydroxybenzamides/-hydroxypropenamides as HDAC inhibitors: design, synthesis, biological evaluation, and docking studies.

Herein, two novel series of -hydroxybenzamides and -hydroxypropenamides incorporating 4-oxoquinazoline and 1,2,3-triazole scaffolds were rationally designed, synthesized, and evaluated for their Histone deacetylase (HDAC) inhibitory and anticancer activities. The synthesized hydroxamic acids were evaluated for HDAC inhibitory activity using nuclear extracts from HeLa cells. -hydroxybenzamide derivatives (7a-i) exhibited stronger HDAC inhibition than their -hydroxypropenamide counterparts (11a-i).

Xiapyrroles A-F: -Alkylpyrrole Alkaloids from the Marine-Derived Actinomycete 1310KO-148.

Six new -alkylpyrrole alkaloids (-) were isolated from the marine-derived actinomycete 1310KO-148 from a sponge sample. The structures of xiapyrroles A-F (-) were elucidated by detailed analysis of extensive spectroscopic data, including 1D, 2D NMR, and HRESIMS data. The absolute configurations of , , , and were determined by a comparison of their calculated and experimental electronic circular dichroism (ECD) spectra.

Design, synthesis and biological evaluation of novel hydroxamic acid-derived histone deacetylase inhibitors bearing a 2-oxoindoline scaffold as potential antitumor agents.

Histone deacetylases (HDACs) have emerged as compelling targets in developing anticancer therapeutics. This study outlines the development, synthesis, and biological evaluation of novel hydroxamic acid derivatives featuring a 2-oxoindoline scaffold, which exhibit high HDAC inhibitory activity and potential anticancer effects. Three series of N-hydroxycinnamamides, N-hydroxyheptanamides, and N-hydroxybenzamides were synthesized and assessed for their biological activity.

Geliboluols A-D: Kaurane-Type Diterpenoids from the Marine-Derived Rare Actinomycete .

Four new kaurane-type diterpenoids, geliboluols A-D (-), along with one known analog (), were isolated from the culture broth of the marine-derived rare actinomycete . The structures of compounds - were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR), the MPA method, and by comparing their optical rotation values with those in the literature. The new compounds were evaluated for their cytotoxicity against seven blood cancer cell lines by a CellTiter-Glo (CTG) assay and six solid cancer cell lines by a sulforhodamine B (SRB) assay.

Suppression of dopamine receptor 2 inhibits the formation of human prostate cancer PC‑3‑derived cancer stem cell‑like cells through AMPK inhibition.

Cancer stem cells (CSCs) contribute to the resistance of intractable prostate cancer, and dopamine receptor (DR)D2 antagonists exhibit anticancer activity against prostate cancer and CSCs. Human prostate cancer PC-3 cells were used to generate CSC-like cells, serving as a surrogate system to identify the specific DR subtype the inhibition of which significantly affects prostate-derived CSCs. Additionally, the present study aimed to determine the downstream signaling molecules of this DR subtype that exert more profound effects compared with other DR subtypes.

Exploring structural and biological insights of TEAD through rational design and synthesis of niflumic acid derivatives.

Transcriptional enhanced associate domain (TEAD) transcription factors undergo auto-palmitoylation, which is critical to mediate their function and maintain stability. Targeting the palmitate binding pocket of TEAD holds considerable promise for drug discovery, and it can be characterised into three components: a conserved cysteine, a hydrophobic main pocket, and a hydrophilic side pocket. Endogenous palmitate and several known TEAD inhibitors interact with the cysteine and hydrophobic residues in the deep hydrophobic pocket.

Discovery of organosulfur-based selective HDAC8 inhibitors with anti-neuroblastoma activity.

Histone deacetylases (HDACs) are important epigenetic regulators of gene expression and various cellular processes, and are potential targets for anticancer therapy. In particular, HDAC8 is a promising therapeutic target for childhood neuroblastoma. To date, five HDAC inhibitors have been approved as anticancer drugs; however, all are non-selective HDAC inhibitors with various side effects.

Albusamides A-G: Hydroxylated Fatty Amine Derivatives from the Deep-Sea-Derived Actinomycete 228DD-066 and Their Cytotoxic Activity.

A series of new hydroxylated fatty amine derivatives, albusamides A-G (-), along with four known compounds (-), which are reported for the first time from a natural source, were isolated from the culture broth of 228DD-066 derived from a deep-sea sediment sample gathered off the coast of Dokdo Island, Republic of Korea. Their structures were elucidated through the comprehensive analysis of 1D and 2D NMR spectra and HRESIMS, and absolute configurations were determined using the modified Mosher's method. Biological evaluations against solid and blood cancer cell lines revealed that these new metabolites have moderate to strong cytotoxic activity.

A small molecule compound 759 inhibits the wnt/beta-catenin signaling pathway via increasing the Axin protein stability.

Wnt/β-catenin signaling plays important role in cancers. Compound 759 is one of the compounds previously screened to identify inhibitors of the Wnt/β-catenin pathway in A549 cells [Lee et al. in Bioorg Med Chem Lett 20:5900-5904, 2010].

Labdane-Type Diterpenoids from and Their Antimicrobial and Cytotoxic Activities.

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, , resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (-), epoxylabdans A and B ( and ), along with one known analog (). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL.

Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (-), and one known analog, argovin (), were isolated from the marine-derived fungus sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data.

Rifamycin-Related Polyketides from a Marine-Derived Bacterium and Their Cytotoxic Activity.

Eight rifamycin-related polyketides were isolated from the culture broth of a marine-derived bacterium , including five known (- and ) and three new derivatives (, , and ). The structures of the new compounds were determined by means of spectroscopic methods (HRESIMS and 1D, 2D NMR) and a comparison of their experimental data with those previously reported in the literature. The isolated compounds were evaluated for their cytotoxicity against one normal, six solid, and seven blood cancer cell lines and showed moderate activity against all the tested cell lines with GI values ranging from 2.

VDUP1 Deficiency Promotes the Severity of DSS-Induced Colitis in Mice by Inducing Macrophage Infiltration.

The loss of vitamin D upregulated protein 1 (VDUP1) has been implicated in the pathogenesis of various inflammation-related diseases. Notably, reduced expression of VDUP1 has been observed in clinical specimens of ulcerative colitis (UC). However, the role of VDUP1 deficiency in colitis remains unclear.

Sesquiterpenes from and Their Cytotoxic Activity.

Nine sesquiterpenes, including eight pentalenenes (-) and one bolinane derivative (), were isolated from the culture broth of a marine-derived actinobacterium 213DD-006. Among them, , , , and were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations.

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis and Bioevaluation.

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides (4 a-i, 7 a-g) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI-H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a-i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a-g in all biological assays.

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium and Their Antimicrobial and Cytotoxic Activities.

Two new alkaloids, streptopyrroles B and C ( and ), were discovered through a chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, , along with four known analogs (-). The structures of the new compounds were elucidated by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and a comparison of their experimental data with literature values. The new compounds were evaluated for their antimicrobial activity by standard broth dilution assay, and the tested compounds showed significant activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 0.

New Angucycline Glycosides from a Marine-Derived Bacterium .

Chemical investigation of the ethyl acetate extract from the culture broth of the marine-derived actinobacterium 156VN-095 led to the isolation of three hitherto undescribed angucycline glycosides, including urdamycins W and X ( and ) and grincamycin U (), as well as their seven known congeners. The structures of the new compounds were elucidated by means of spectroscopic methods (HRESIMS, 1D and 2 D NMR) and comparison of their experimental data with literature values. Compounds - and were evaluated for their anti-Gram-positive bacterial effect and cytotoxicity against six cancer cell lines.

Protection against Lipopolysaccharide-Induced Endotoxemia by Terrein Is Mediated by Blocking Interleukin-1β and Interleukin-6 Production.

Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia in mice and characterized the potential mechanisms of action.

Aspersterols A-D, Ergostane-Type Sterols with an Unusual Unsaturated Side Chain from the Deep-Sea-Derived Fungus .

Four previously undescribed ergostane-type sterols, aspersterols A-D (-), were isolated from a deep-sea-derived fungus, IV17-109. The structures of the new compounds were determined by extensive analyses of their spectroscopic data, pyridine-induced deshielding effect, Mosher's method, and electronic circular dichroism calculations. The key feature of these sterols is the presence of a rare unsaturated side chain with conjugated double bonds at Δ and Δ.

Targeted Induction of Endogenous VDUP1 by Small Activating RNA Inhibits the Growth of Lung Cancer Cells.

Recent studies have reported that small double-strand RNAs (dsRNAs) can activate endogenous genes via an RNA-based promoter targeting mechanism termed RNA activation (RNAa). In the present study, we showed that dsVDUP1-834, a novel small activating RNA (saRNA) targeting promoter of vitamin D up-regulated protein 1 (VDUP1) gene, up-regulated expression of VDUP1 at both mRNA and protein levels in A549 lung cancer cells. We also demonstrated that dsVDUP1-834 inhibited cell proliferation in A549 lung cancer cells.

New Glycosylated Secondary Metabolites from Marine-Derived Bacteria.

Three new glycosylated secondary metabolites, including a new indole alkaloid, pityriacitrin D (), and two new trehalose lipids ( and ), together with three known compounds (-) were isolated from two marine-derived bacterial strains, 168CLC-66.1 and IV19-045. The structures of - were determined by extensive analysis and comparison of their spectroscopic data with literature values.

Design, Synthesis, and Cytotoxicity and Topoisomerase I/IIα Inhibition Activity of Pyrazolo[4,3-]quinoline Derivatives.

With the several targets of cancer treatment, inhibition of DNA topoisomerase activity is one of the well-known focuses in cancer chemotherapy. Here, we describe the design and synthesis of a novel series of pyrazolo[4,3-]quinolines with potential anticancer/topoisomerase inhibition activity. Forty newly designed pyrazolo[4,3-]quinoline derivatives were synthesized via inverse imino Diels-Alder reaction.