ABSTRACT
Abstract Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 µM, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors
Subject(s)
Platinum/pharmacology , Anticarcinogenic Agents/classification , Histone Deacetylase Inhibitors/adverse effects , Lung Neoplasms/pathologyABSTRACT
Objective To study the chemical constituents of the underground parts of Astragalus tatsienensis var. incanus. Methods The compounds were separated and purified by RP18, Sephadex LH-20 column chromatography, as well as preparative liquid chromatography. The structures of the isolated compounds were determined by means of modern spectroscopic analysis and physicochemical properties. Results Four compounds were isolated from the methanol extract of the underground part of A. tatsienensis var. incanus, and identified as 3β-O-α-L-rhamnopyranosyl (1→2)-β-D-galactopyranosyl (1→2)-β-D-glucuronopyranosyl- 22β-hydroxy-11-oxo-olean-12-ene (1), hyperoside (2), wighteone (3), and 4-hydroxybenzoic acid (4). Conclusion Compounds 2-4 are isolated from this plant for the first time, and compound 1 is a new triterpene glycosides compound, named astratatincoside A.
ABSTRACT
Objective: To investigate the chemical constituents from the whole plants of Scutellaria viscidula. Methods: By means of preparative HPTLC and column chromatography over silica gel and Sephadex LH-20, the chemical constituents were isolated and purified. Their structures were elucidated by physico-chemical properties and spectral analyses. Results: A total of 22 compounds were isolated and identified as: 5-hydroxy-7,8-dimethoxyflavone (1), chrysin (2), 5,7-dimethoxyflavone (3), 5,7,4’-trihydroxy- 6-methoxyflavone (4), 5,7,4’-trihydroxyflavonoid (5), 5,7,2’-trihydroxy-8-methoxyflavone (6), 5,7-dihydroxy-8,2’-dimethoxyflavone (7), 5,7,2’-trihydroxy-6-methoxyflavanone (8), 5-hydroxy-6,7,8-trimethoxyflavone (9), 5,6,7-trimethoxyflavone (10), 3,5-dimethoxy- 6,7-methylenedioxyflavone (11), 5,2’-dihydroxy-7,8,6’-trimethoxyflavone (12), 5,2’-dihydroxy-7,8,6’-trimethoxyflavanone (13), 5,7-dimethoxyflavanone (14), 7-methoxy-chrysin (15), 2’-hydroxy-5,7,8-trimethoxyflavone (16), ferulic acid (17), 4-hydroxy-3- methoxybenzoic acid (18), p-hydroxy-benzaldehyde (19), 3,5-dimethoxy-4-hydroxybenzoic acid (20), 7-hydroxy-6-methoxy-coumarin (21), 6,7-dihydroxyl-coumarin (22). Conclusion: Compounds 1, 3-16, 18 and 20 are isolated from Scutellaria viscidula for the first time.
ABSTRACT
Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K+ across the cellular membrane. Methods: Chemical compounds from Dendrocalamus asper bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from Xenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from −80 mV with 20 mV stepup until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with n ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control. Results: All concentration showed statistically significant results with P < 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play any significant roles. Conclusion: 4-hydroxybenzoic acid was found to be able to enhance the inactivation of Kv1.4 by lowering the membrane potential so that the abnormal neuronal firing can be inhibited. With IC50 slightly higher than 10 μM, increasing concentrations (100 μM, 1 mM and 2.5 mM) had shown to exhibit toxicity effects. The best concentration from this study is 10 μM with Hill slope of 0.1799.
ABSTRACT
CoQ10 has been used not only as a medicine but also as food supplements because of its various physiological and biochemical activities. A full-factorial central composite design and response surface methodology were used for optimizing three precursors Solanesol, 4-hydroxybenzoic acid and methionine to maximize the production of CoQ10 by Rhodopseudomonas palustris J001. The optimization of the model predicted a maximum response 40.6 [(mg CoQ10)(g dried biomass)-1] CoQ10 production with 124.8 mg l-1 Solanesol, 267.7 mg l-14-hydroxybenzoic acid and 130.2 mg l-1 methionine, respectively. A new combination was prepared according to the result. The observed response was 40.5 ± 0.2 [(mg CoQ10)(g dried biomass)-1] and was 109.8%higher than in the control with no addition of the three precursors.
ABSTRACT
CoQ10 has been used not only as a medicine but also as food supplements because of its various physiological and biochemical activities. A full-factorial central composite design and response surface methodology were used for optimizing three precursors Solanesol, 4-hydroxybenzoic acid and methionine to maximize the production of CoQ10 by Rhodopseudomonas palustris J001. The optimization of the model predicted a maximum response 40.6 [(mg CoQ10)(g dried biomass)-1] CoQ10 production with 124.8 mg l-1 Solanesol, 267.7 mg l-14-hydroxybenzoic acid and 130.2 mg l-1 methionine, respectively. A new combination was prepared according to the result. The observed response was 40.5 ± 0.2 [(mg CoQ10)(g dried biomass)-1] and was 109.8%higher than in the control with no addition of the three precursors.
ABSTRACT
CoQ10 has been used not only as a medicine but also as food supplements because of its various physiological and biochemical activities. A full-factorial central composite design and response surface methodology were used for optimizing three precursors Solanesol, 4-hydroxybenzoic acid and methionine to maximize the production of CoQ10 by Rhodopseudomonas palustris J001. The optimization of the model predicted a maximum response 40.6 [(mg CoQ10)(g dried biomass)-1] CoQ10 production with 124.8 mg l-1 Solanesol, 267.7 mg l-14-hydroxybenzoic acid and 130.2 mg l-1 methionine, respectively. A new combination was prepared according to the result. The observed response was 40.5 ± 0.2 [(mg CoQ10)(g dried biomass)-1] and was 109.8%higher than in the control with no addition of the three precursors.