Comparative molecular field analysis (CoMFA), a three dimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a series of diindolylmethane (DIM) analogs to study the relationship betwe...Comparative molecular field analysis (CoMFA), a three dimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a series of diindolylmethane (DIM) analogs to study the relationship between their structure and their induction of CYP 1A1-associated ethoxyresorufin-O-deethylase (EROD) activity. A DISCO model of pharmacophore was derived to guide the superposition of the compounds. The coefficient of cross-validation (q 2) and non cross-validation (r 2) for the model established by the study are 0.827 and 0.988 respectively, the value of variance ratio (F) is 103.53 and standard error estimate (SEE) is 0.044. These values indicate that the CoMFA model derived is significant and might have a good prediction for the catalytic activity of DIM compounds. As a consequence, the predicted activity values of new designed compounds were all higher than that of the reported value.展开更多
Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive co...Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive compounds with excellent therapeutic efficacy. Numerous phytochemicals from nature have been investigated for anticancer properties. In this review article, we discuss several natural compounds, which have shown anti-cancer activity. Natural compounds induce cell cycle arrest, activate intrinsic and extrinsic apoptosis pathways, generate Reactive Oxygen Species(ROS), and down-regulate activated signaling pathways, resulting in inhibition of cell proliferation, progression and metastasis of cancer. Several preclinical studies have suggested that natural compounds can also increase the sensitivity of resistant cancers to available chemotherapy agents. Furthermore, combining FDA approved anti-cancer drugs with natural compounds results in improved efficacy. On the basis of these exciting outcomes of natural compounds against several cancer types, several agents have already advanced to clinical trials. In conclusion, preclinical results and clinical outcomes against cancer suggest promising anticancer efficacy of agents from natural sources.展开更多
Indole-3-carbinol(I3C) and diindolylmethane(DIM) are naturally derived dietary phytochemicals with promising anti-cancer properties that have been demonstrated both in vitro and in vivo. Using reversed-phase ultra-per...Indole-3-carbinol(I3C) and diindolylmethane(DIM) are naturally derived dietary phytochemicals with promising anti-cancer properties that have been demonstrated both in vitro and in vivo. Using reversed-phase ultra-performance liquid chromatography(UPLC) coupled with mass spectrometry(MS), a rapid, specific, and high throughput method was developed and validated for the quantification and identification of I3 C, DIM, and other I3 C metabolites in plasma. Samples containing I3 C or DIM and the internal standard 4-methoxy indole(IS) were extracted using a liquid-liquid extraction technique. The mean recovery was 96.21% for I3 C and 108.5% for DIM. Separation was achieved using a Waters Acquity UPLC HSS T3, 1.8 μm, 2.1 mm×150 mm column and acetonitrile–water gradient elution. The flow rate was 0.3 m L/min and the run time was 9 min. The limits of detection and quantification for I3 C and DIM were 15 ng/m L and 25 ng/m L, respectively. Calibration curves for I3 C and DIM were linear(r2>0.99) over a concentration range of 0.025–20 μg/m L. Precision, accuracy, and stability analysis fulfilled the CDER guidelines criteria. The method was successfully applied to the determination of the pharmacokinetic parameters of I3 C or DIM after oral, intravenous, or intraperitoneal administration to Sprague Dawley rats. The method described here is superior over existing analytical methods for I3 C and its metabolites in terms of sensitivity, speed, and separation.展开更多
文摘Comparative molecular field analysis (CoMFA), a three dimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a series of diindolylmethane (DIM) analogs to study the relationship between their structure and their induction of CYP 1A1-associated ethoxyresorufin-O-deethylase (EROD) activity. A DISCO model of pharmacophore was derived to guide the superposition of the compounds. The coefficient of cross-validation (q 2) and non cross-validation (r 2) for the model established by the study are 0.827 and 0.988 respectively, the value of variance ratio (F) is 103.53 and standard error estimate (SEE) is 0.044. These values indicate that the CoMFA model derived is significant and might have a good prediction for the catalytic activity of DIM compounds. As a consequence, the predicted activity values of new designed compounds were all higher than that of the reported value.
基金supported in part by NIH/National Cancer Institute R01 grant CA129038(to S.K.S)MEST grant 2012–0005755(to S.H.K)
文摘Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive compounds with excellent therapeutic efficacy. Numerous phytochemicals from nature have been investigated for anticancer properties. In this review article, we discuss several natural compounds, which have shown anti-cancer activity. Natural compounds induce cell cycle arrest, activate intrinsic and extrinsic apoptosis pathways, generate Reactive Oxygen Species(ROS), and down-regulate activated signaling pathways, resulting in inhibition of cell proliferation, progression and metastasis of cancer. Several preclinical studies have suggested that natural compounds can also increase the sensitivity of resistant cancers to available chemotherapy agents. Furthermore, combining FDA approved anti-cancer drugs with natural compounds results in improved efficacy. On the basis of these exciting outcomes of natural compounds against several cancer types, several agents have already advanced to clinical trials. In conclusion, preclinical results and clinical outcomes against cancer suggest promising anticancer efficacy of agents from natural sources.
基金R01 CA118947R01 CA152826 from National Cancer Institute(NCI)+2 种基金R01AT007065 from the National Center for Complementary and Alternative Medicines(NCCAM)the Office of Dietary Supplements(ODS)the National Institute of Health Grant R01 CA073674
文摘Indole-3-carbinol(I3C) and diindolylmethane(DIM) are naturally derived dietary phytochemicals with promising anti-cancer properties that have been demonstrated both in vitro and in vivo. Using reversed-phase ultra-performance liquid chromatography(UPLC) coupled with mass spectrometry(MS), a rapid, specific, and high throughput method was developed and validated for the quantification and identification of I3 C, DIM, and other I3 C metabolites in plasma. Samples containing I3 C or DIM and the internal standard 4-methoxy indole(IS) were extracted using a liquid-liquid extraction technique. The mean recovery was 96.21% for I3 C and 108.5% for DIM. Separation was achieved using a Waters Acquity UPLC HSS T3, 1.8 μm, 2.1 mm×150 mm column and acetonitrile–water gradient elution. The flow rate was 0.3 m L/min and the run time was 9 min. The limits of detection and quantification for I3 C and DIM were 15 ng/m L and 25 ng/m L, respectively. Calibration curves for I3 C and DIM were linear(r2>0.99) over a concentration range of 0.025–20 μg/m L. Precision, accuracy, and stability analysis fulfilled the CDER guidelines criteria. The method was successfully applied to the determination of the pharmacokinetic parameters of I3 C or DIM after oral, intravenous, or intraperitoneal administration to Sprague Dawley rats. The method described here is superior over existing analytical methods for I3 C and its metabolites in terms of sensitivity, speed, and separation.
