Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with few treatment options. A promising TNBC treatment approach is targeting the oncogenic signaling pathways pivotal to TNBC initiation and progression. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving TNBC malignant transformation, highlighting STAT3 as a promising TNBC therapeutic target.

Dehydroxyhispolon Methyl Ether, A Hispolon Derivative, Inhibits WNT/β-Catenin Signaling to Elicit Human Colorectal Carcinoma Cell Apoptosis.

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Aberrant activation of WNT/β-catenin signaling present in the vast majority of CRC cases is indispensable for CRC initiation and progression, and thus is a promising target for CRC therapeutics. Hispolon is a fungal-derived polyphenol with a pronounced anticancer effect.

Co-Delivery of Hispolon and Doxorubicin Liposomes Improves Efficacy Against Melanoma Cells.

Hispolon is a small molecular weight polyphenol that has antioxidant, anti-inflammatory, and anti-proliferative activities. Our recent study has demonstrated hispolon as a potent apoptosis inducer in melanoma cell lines. Doxorubicin is a broad spectrum first-line treatment for various kinds of cancers.

Elucidating the anti-melanoma effect and mechanisms of Hispolon.

There is a rapid increase in the incidence of melanoma which has led to a global crisis. Thus, there is a great need for developing novel, safe and effective drugs for the treatment of melanoma. Hispolon is a small molecular weight polyphenol derived from Phellinus linteus, which has antioxidant, anti-inflammatory and anti-proliferative activities.

X-ray crystal structures, density functional theory and docking on deacetylase enzyme for antiproliferative activity of hispolon derivatives on HCT116 colon cancer.

The antiproliferative action of hispolon derivatives is stronger than that of related curcumin against several tumor cell lines. Hispolon size, smaller than curcumin, fits better than curcumin into the active site of HDAC6, an enzyme involved in deacetylation of lysine residues. HDACs are considered potential targets for tumor drug discovery and hydroxamates are known inhibitors of HDACs.

Synthesis, Screening and Docking Analysis of Hispolon Pyrazoles and Isoxazoles as Potential Antitubercular Agents.

Background: Hispolons are natural products known to possess cytoprotective, antioxidant and anti-cancer activities. We have found recently anti TB activity in these compounds. Efforts were made to optimize the structure with bioisosteric replacement of 1,3-diketo functional group with the corresponding pyrazole and isoxazole moieties.

Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase.

Hispolon (HS), a bioactive polyphenol, and its derivatives such as hispolon monomethyl ether (HME), hispolon pyrazole (HP), and hispolon monomethyl ether pyrazole (HMEP) were evaluated for comparative toxicity and antigenotoxic effects. The stability of HS derivatives in biological matrices followed the order HS < HP ≈ HME < HMEP. The cytotoxicity analysis of HS derivatives indicated that HP and HMEP were less toxic than HS and HME, respectively, in both normal and tumor cell types.

Diketo modification of curcumin affects its interaction with human serum albumin.

Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU.

Hispolon Suppresses LPS- or LTA-Induced iNOS/NO Production and Apoptosis in BV-2 Microglial Cells.

Hispolon (HIS) is an active polyphenol compound derived from Phellinus linteus (Berkeley & Curtis), and our previous study showed that HIS effectively inhibited inflammatory responses in macrophages [Yang, L.Y., S.

Synthesis, screening and docking analysis of hispolon analogs as potential antitubercular agents.

A series of 20 hispolons/dihydrohispolons were synthesized and characterized by spectral data. These compounds were subjected to in vitro antitubercular activity screening against Mycobacterium tuberculosis (H37Rv) strain. The synthesized compounds showed varied antitubercular activity ranging from 100 to 1.

Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors.

Hispolon (HS), a natural polyphenol found in medicinal mushrooms, and its isoxazole (HI) and pyrazole (HP) derivatives have been examined for free radical reactions and in vitro antioxidant activity. Reaction of these compounds with one-electron oxidant, azide radicals ([Formula: see text]) and trichloromethyl peroxyl radicals ([Formula: see text]), model peroxyl radicals, studied by nanosecond pulse radiolysis technique, indicated formation of phenoxyl radicals absorbing at 420 nm with half life of few hundred microseconds (μs). The formation of phenoxyl radicals confirmed that the phenolic OH is the active centre for free radical reactions.

The in vitro antitumor activity of arene-ruthenium(II) curcuminoid complexes improves when decreasing curcumin polarity.

The antitumor activity of ruthenium(II) arene (p-cymene, benzene, hexamethylbenzene) derivatives containing modified curcumin ligands (HCurcI=(1E,4Z,6E)-5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)hepta-1,4,6-trien-3-one and HCurcII=(1E,4Z,6E)-5-hydroxy-1,7-bis(4-methoxyphenyl)hepta-1,4,6-trien-3-one) is described. These have been characterized by IR, ESI-MS and NMR spectroscopy. The X-ray crystal structure of HCurcI has been determined and compared with its related Ru complex.

Design, synthesis and in vitro cell-based evaluation of the anti-cancer activities of hispolon analogs.

Phytochemicals play an important role in cancer therapy. Hispolon and 26 of its analogs (9 known and 17 new) were synthesized and evaluated for their antiproliferative activities in a panel of six independent human cancer cell lines using the in vitro cell-based MTT assay. Among the hispolon analogs tested, compound VA-2, the most potent overall, produced its most significant effect in the colon cancer cell lines HCT-116 (IC₅₀ 1.

Hispolon inhibition of inflammatory apoptosis through reduction of iNOS/NO production via HO-1 induction in macrophages.

Ethnopharmacological Relevance: Phellinus linteus (Berkeley & Curtis), a well-known medical fungus, has long been used as a traditional medicine in Oriental countries to treat various diseases, and hispolon (HIS) is one of its bioactive components. HIS is known to possess potent antineoplastic and antiviral properties; however, its effect on inflammatory apoptosis is still undefined.

Materials And Methods: RAW264.

Determination of Catechin and Epicatechin Content in Chocolates by High-Performance Liquid Chromatography.

A simple and sensitive reversed phase high-performance liquid chromatographic (HPLC) method has been developed for the determination of catechin and epicatechin in cocoa powder and chocolates. The separation was achieved on a reversed phase C 18 column (TARGA) 5 μm by gradient elution with a flow rate of 1.0 mL/minute with an operating temperature of 30°C and detection with a UV-Visible detector was at 280 nm.

Design of a novel nucleoside analog as potent inhibitor of the NAD dependent deacetylase, SIRT2.

Sirtuins (class III histone deacetylase) are evolutionarily conserved NAD(+)-dependent enzymes that catalyze the deacetylation of acetyl-lysine residues of histones and other target proteins. Because of their associations in various pathophysiological conditions, the identification of small molecule modulators has been of significant interest. In the present study, virtual screening was carried out with NCI Diversity Set II using crystal structure of hSIRT2 (PDB ID: 1J8F) as a model for the docking procedure to find potential compounds, which were then subjected to experimental tests for their in vitro SIRT2 inhibitory activity.

Bisdemethylcurcumin and structurally related hispolon analogues of curcumin exhibit enhanced prooxidant, anti-proliferative and anti-inflammatory activities in vitro.

Curcumin, a component of turmeric (Curcuma longa), exhibits anti-inflammatory and anti-proliferative activities through the generation of reactive oxygen species (ROS). Curcumin (diferuloylmethane) contains two hydroxyl, two methoxy and two phenyl groups but how these groups contribute to its activity is poorly understood. We synthesized analogues that varied in inclusion of these groups and compared their activity.

Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation.

Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 microm with no activity against COX-1 enzyme.

Synthesis, structural revision, and antioxidant activities of antimutagenic homoisoflavonoids from Hoffmanosseggia intricata.

Intricatinol and intricatin, the two homoisoflavonoids isolated from Hoffmanosseggia intricata, and two analogs have been synthesized from pyrogallol in three steps. The spectral data of synthetic intricatinol are in good agreement with those of natural metabolite, but the spectral data of intricatin are not corroborative with those of the natural product. The structure of intricatin has been thus revised to 8-methoxybonducellin, a compound isolated from Caesalpinia pulcherrima.

Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots of Withania somnifera.

A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic evaluation revealed its identity as a dimer with an unusual thioether linkage. Compound 1 displayed growth inhibition against human gastric (AGS), breast (MCF-7), central nervous system (SF-268), colon (HCT-116), and lung (NCI H460) cancer cell lines, with IC50 values in the range 0.

Estimation of twelve bacopa saponins in Bacopa monnieri extracts and formulations by high-performance liquid chromatography.

A simple and sensitive reversed phase high performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of twelve bacopa saponins present in the extracts of the Indian Medicinal Plant, Bacopa monnieri. The separation was achieved on a reversed phase C(18) column (Luna C(18)), 5 microm by isocratic elution with 0.05 M sodium sulphate buffer (pH 2.

Standardisation of Gymnema sylvestre R.Br. by high-performance thin-layer chromatography: an improved method.

An improved high-performance thin-layer chromatographic (HPTLC) method for the standardisation of Gymnema sylvestre is reported. The method involves the initial hydrolysis of gymnemic acids, the active ingredients, to a common aglycone followed by the quantitative estimation of gymnemagenin. The present method rectifies an error found in an HPTLC method reported recently.

Regulation of vascular responses to inflammation: inducible matrix metalloproteinase-3 expression in human microvascular endothelial cells is sensitive to antiinflammatory Boswellia.

Endothelial cells are critical elements in the pathophysiology of inflammation. Tumor necrosis factor (TNF) alpha potently induces inflammatory responses in endothelial cells. Recently we have examined the genetic basis of the antiinflammatory effects of Boswellia extract (BE) in a system of TNFalpha-induced gene expression in human microvascular endothelial cells (HMECs).

Synthesis, stereochemical assignments, and biological activities of homoisoflavonoids.

A series of four naturally occurring homoisoflavonoids and eight analogs have been synthesized starting from an appropriately substituted phenol through chroman-4-one, in four steps. The products were assigned as E-isomers based on NMR spectroscopic data. The E-isomers were converted into Z-isomers by photoisomerization.