Epidemiological studies indicate that treatment with metformin, an AMP-activated protein kinase (AMPK) activator, reduces the incidence of cancers. Activation of AMPK has also been reported to oppose tumor progression...Epidemiological studies indicate that treatment with metformin, an AMP-activated protein kinase (AMPK) activator, reduces the incidence of cancers. Activation of AMPK has also been reported to oppose tumor progression in diverse types of cancers and offers promising cancer therapy. Furthermore, AMPK is a primary regulator of energy metabolism and has also been implicated in cell cycle progression, angiogenesis, cell transformation, migration, and cancer. We have recently synthesized novel flavonoids, namely, triphenylmethanol derivatives (TPMs), but the effectiveness of the TPMs on the activity of AMPK remains unclear. We hypothesized that the novel TPMs would inhibit cancer cell proliferation through the activation of AMPK isoforms in cells. The effects of TPMs on prostate cells (PC-3) were investigated. Cells were exposed to TPMs for either 12 or 24 hr. at the respective doses of 0, 25, 50 100, and 200 µM based on the cell viability studies by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) (MTT) assay. The results indicate that cells exposed to the respective doses of TPMs increased both phospho- and total-AMPKα1 in a dose- and time-dependent manner. The effects of the increases for the phospho- and total-AMPKα in cells were greater for the 24-hr than the 12-hr. incubation. Further studies are currently going on to elucidate the specificities of the said insults in increasing the phospho- and total-AMPKα activities and for the other respective isoforms.展开更多
Some Triptorelin<sup>®</sup> (TRP) conjugates of triphenylmethanol derivatives (TPMs) with optimized hydrophobicity were synthesized by reacting 2-substituted methoxy benzenes with 1,3,5-trioxane, fol...Some Triptorelin<sup>®</sup> (TRP) conjugates of triphenylmethanol derivatives (TPMs) with optimized hydrophobicity were synthesized by reacting 2-substituted methoxy benzenes with 1,3,5-trioxane, followed by the conjugation with TRP and sebacic acid to produce TRP-TPMs derivatives. Comparative antiproliferative assays between TRP-TPMs conjugates and the corresponding non-covalent physical mixtures of the TPMs derivatives and TRP were used to treat human acute lymphoblastic leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3) and mouse preadipocytes (3T3-L1) cells. TRP-TPMs conjugates at the 50 μM inhibited cell proliferation in CCRF-CEM, SK-OV-3 and 3T3-L1 cells by 21% - 37%, 24% - 73%, 37% - 56%, respectively following incubation for 72 h. These findings indicate that TRP-TPMs derivatives have the potential to enhance the biological activity of TRP.展开更多
Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role...Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role in heart disease, cancer and other diseases. If the body cannot process and remove free radicals efficiently, oxidative stress can result. This can harm cells and body function. Free radicals are also known as reactive oxygen species (ROS). In this research, Triptorelin®(TRP) conjugates of triphenylmethanol derivatives (TPMs) were synthesized to evaluate their in vitro lipid peroxidation potency. Comparative lipid peroxidation assays between TRP-TPMs conjugates and the corresponding TPMs derivatives were measured using thiobarbituric reactive substance (TBARS) in a dose- and time-dependent manner following the Fenton’s pathway. Overall, TBARS decreased between 20% - 30% for the treated samples of synthesized conjugates compared to their respective control physical mixtures. These data suggest that TRP-TPMs derivatives can be used to improve the biological activity of TRP.展开更多
Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during ...Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin®conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.展开更多
Polyphenols are naturally occurring compounds found largely in fruits, vegetables, cereals and beverages. Currently, there is much interest in the potential health benefits of dietary plant polyphenols as antioxidants...Polyphenols are naturally occurring compounds found largely in fruits, vegetables, cereals and beverages. Currently, there is much interest in the potential health benefits of dietary plant polyphenols as antioxidants. The effect of polyphenols on human cancer cells is most often protective and induces a reduction in the number of tumors or rate of growth. During our course of study on anticancer prodrugs, twelve triphenylmethanol and one tris(2-(hydroxymethyl) phenol derivatives were synthesized as a carrier of several drugs with optimized lipophilicity. Besides application of these compounds as a foundation for anticancer drug delivery systems, these compounds were evaluated as indicators for the acid-base volumetric titration of a standard solution of hydrochloric acid with a standard solution of sodium hydroxide. The experiments indicated a moderate-to-sharp color transition of the solutions near the neutralization point for most indicators. These indicators may have potential applications for acid-base titrations in a narrow range.展开更多
Crystal habit and crystal form are critical elements in determining product properties and functions. In this work, we developed a microfluidic antisolvent crystallization technique to rapidly screen and accurately co...Crystal habit and crystal form are critical elements in determining product properties and functions. In this work, we developed a microfluidic antisolvent crystallization technique to rapidly screen and accurately control the solid form and crystal habit of triphenylmethanol(Ph_(3)COH). This advanced technique separates the primary mixing of solutions from crystal formation(nucleation and growth) by introducing the microfluidic device, avoiding clogging in microchannels to obtain high-quality crystals. The results show that we can achieve controllable preparation of pure 2Ph_(3)COH·DMSO(DMSO solvate), pure Ph_(3)COH(form β), and mixed crystals with different mass ratios. Moreover, the microscale can prompt the DMSO solvate to grow into hexagonal sheet-like and bulk crystals. We can regulate the aspect ratio of hexagonal sheet-like crystals in binary solvents and control the crystal habit of the form β to transition between long needle-like shapes and short hexagonal prisms in DMF-H_(2)O. Meanwhile, we revealed that the solvent ratio, the antisolvent flow rate, and the initial concentration of Ph_(3)COH are the main factors affecting the solid form selectivity and morphology transition. Such a novel method would be considered as a promising technique to be extended to screen and control key crystallization parameters of other substances.展开更多
文摘Epidemiological studies indicate that treatment with metformin, an AMP-activated protein kinase (AMPK) activator, reduces the incidence of cancers. Activation of AMPK has also been reported to oppose tumor progression in diverse types of cancers and offers promising cancer therapy. Furthermore, AMPK is a primary regulator of energy metabolism and has also been implicated in cell cycle progression, angiogenesis, cell transformation, migration, and cancer. We have recently synthesized novel flavonoids, namely, triphenylmethanol derivatives (TPMs), but the effectiveness of the TPMs on the activity of AMPK remains unclear. We hypothesized that the novel TPMs would inhibit cancer cell proliferation through the activation of AMPK isoforms in cells. The effects of TPMs on prostate cells (PC-3) were investigated. Cells were exposed to TPMs for either 12 or 24 hr. at the respective doses of 0, 25, 50 100, and 200 µM based on the cell viability studies by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) (MTT) assay. The results indicate that cells exposed to the respective doses of TPMs increased both phospho- and total-AMPKα1 in a dose- and time-dependent manner. The effects of the increases for the phospho- and total-AMPKα in cells were greater for the 24-hr than the 12-hr. incubation. Further studies are currently going on to elucidate the specificities of the said insults in increasing the phospho- and total-AMPKα activities and for the other respective isoforms.
文摘Some Triptorelin<sup>®</sup> (TRP) conjugates of triphenylmethanol derivatives (TPMs) with optimized hydrophobicity were synthesized by reacting 2-substituted methoxy benzenes with 1,3,5-trioxane, followed by the conjugation with TRP and sebacic acid to produce TRP-TPMs derivatives. Comparative antiproliferative assays between TRP-TPMs conjugates and the corresponding non-covalent physical mixtures of the TPMs derivatives and TRP were used to treat human acute lymphoblastic leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3) and mouse preadipocytes (3T3-L1) cells. TRP-TPMs conjugates at the 50 μM inhibited cell proliferation in CCRF-CEM, SK-OV-3 and 3T3-L1 cells by 21% - 37%, 24% - 73%, 37% - 56%, respectively following incubation for 72 h. These findings indicate that TRP-TPMs derivatives have the potential to enhance the biological activity of TRP.
文摘Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role in heart disease, cancer and other diseases. If the body cannot process and remove free radicals efficiently, oxidative stress can result. This can harm cells and body function. Free radicals are also known as reactive oxygen species (ROS). In this research, Triptorelin®(TRP) conjugates of triphenylmethanol derivatives (TPMs) were synthesized to evaluate their in vitro lipid peroxidation potency. Comparative lipid peroxidation assays between TRP-TPMs conjugates and the corresponding TPMs derivatives were measured using thiobarbituric reactive substance (TBARS) in a dose- and time-dependent manner following the Fenton’s pathway. Overall, TBARS decreased between 20% - 30% for the treated samples of synthesized conjugates compared to their respective control physical mixtures. These data suggest that TRP-TPMs derivatives can be used to improve the biological activity of TRP.
文摘Leuprorelin®(LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin®conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.
文摘Polyphenols are naturally occurring compounds found largely in fruits, vegetables, cereals and beverages. Currently, there is much interest in the potential health benefits of dietary plant polyphenols as antioxidants. The effect of polyphenols on human cancer cells is most often protective and induces a reduction in the number of tumors or rate of growth. During our course of study on anticancer prodrugs, twelve triphenylmethanol and one tris(2-(hydroxymethyl) phenol derivatives were synthesized as a carrier of several drugs with optimized lipophilicity. Besides application of these compounds as a foundation for anticancer drug delivery systems, these compounds were evaluated as indicators for the acid-base volumetric titration of a standard solution of hydrochloric acid with a standard solution of sodium hydroxide. The experiments indicated a moderate-to-sharp color transition of the solutions near the neutralization point for most indicators. These indicators may have potential applications for acid-base titrations in a narrow range.
基金supported by the National Natural Science Foundation of China (No.22278128)。
文摘Crystal habit and crystal form are critical elements in determining product properties and functions. In this work, we developed a microfluidic antisolvent crystallization technique to rapidly screen and accurately control the solid form and crystal habit of triphenylmethanol(Ph_(3)COH). This advanced technique separates the primary mixing of solutions from crystal formation(nucleation and growth) by introducing the microfluidic device, avoiding clogging in microchannels to obtain high-quality crystals. The results show that we can achieve controllable preparation of pure 2Ph_(3)COH·DMSO(DMSO solvate), pure Ph_(3)COH(form β), and mixed crystals with different mass ratios. Moreover, the microscale can prompt the DMSO solvate to grow into hexagonal sheet-like and bulk crystals. We can regulate the aspect ratio of hexagonal sheet-like crystals in binary solvents and control the crystal habit of the form β to transition between long needle-like shapes and short hexagonal prisms in DMF-H_(2)O. Meanwhile, we revealed that the solvent ratio, the antisolvent flow rate, and the initial concentration of Ph_(3)COH are the main factors affecting the solid form selectivity and morphology transition. Such a novel method would be considered as a promising technique to be extended to screen and control key crystallization parameters of other substances.
