The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Chengguo Xing - One of the best experts on this subject based on the ideXlab platform.
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inhibition of mitogen activated protein kinases increases the sensitivity of a549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog
Biochemical and Biophysical Research Communications, 2012Co-Authors: Janel K Warmka, Eric L Solberg, Nicholette A Zeliadt, Balasubramanian Srinivasan, Aaron T Charlson, Chengguo Xing, Elizabeth V WattenbergAbstract:We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.
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structure activity relationship studies of chalcone leading to 3 hydroxy 4 3 4 5 tetramethoxychalcone and its analogues as potent nuclear factor κb inhibitors and their anticancer activities
Journal of Medicinal Chemistry, 2009Co-Authors: Balasubramanian Srinivasan, Thomas E Johnson, Rahul Lad, Chengguo XingAbstract:Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-κB) activation. The structures of chalcone-based NF-κB inhibitors vary significantly that there is minimum information about their structure−activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-κB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-κB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-κB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-κB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-κB inhibitory activities, sug...
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structure activity relationship studies of chalcone leading to 3 hydroxy 4 3 4 5 tetramethoxychalcone and its analogues as potent nuclear factor κb inhibitors and their anticancer activities
Journal of Medicinal Chemistry, 2009Co-Authors: Balasubramanian Srinivasan, Thomas E Johnson, Rahul Lad, Chengguo XingAbstract:Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.
Balasubramanian Srinivasan - One of the best experts on this subject based on the ideXlab platform.
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inhibition of mitogen activated protein kinases increases the sensitivity of a549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog
Biochemical and Biophysical Research Communications, 2012Co-Authors: Janel K Warmka, Eric L Solberg, Nicholette A Zeliadt, Balasubramanian Srinivasan, Aaron T Charlson, Chengguo Xing, Elizabeth V WattenbergAbstract:We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.
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structure activity relationship studies of chalcone leading to 3 hydroxy 4 3 4 5 tetramethoxychalcone and its analogues as potent nuclear factor κb inhibitors and their anticancer activities
Journal of Medicinal Chemistry, 2009Co-Authors: Balasubramanian Srinivasan, Thomas E Johnson, Rahul Lad, Chengguo XingAbstract:Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-κB) activation. The structures of chalcone-based NF-κB inhibitors vary significantly that there is minimum information about their structure−activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-κB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-κB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-κB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-κB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-κB inhibitory activities, sug...
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structure activity relationship studies of chalcone leading to 3 hydroxy 4 3 4 5 tetramethoxychalcone and its analogues as potent nuclear factor κb inhibitors and their anticancer activities
Journal of Medicinal Chemistry, 2009Co-Authors: Balasubramanian Srinivasan, Thomas E Johnson, Rahul Lad, Chengguo XingAbstract:Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.
Ahmed Kamal - One of the best experts on this subject based on the ideXlab platform.
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the design and development of imidazothiazole chalcone derivatives as potential anticancer drugs
Expert Opinion on Drug Discovery, 2013Co-Authors: Ahmed Kamal, Methuku Kashi Reddy, Aparna ViswanathAbstract:Introduction: Imidazothiazole derivatives have long been therapeutically used for the treatment of various diseases. In recent years, the imidazothiazole and chalcone moieties have emerged as important pharmacophores in the development of antitumor agents. Imidazothiazole–chalcone conjugates can be accessed by covalently binding these two powerful pharamacophore units. These conjugates are known to exhibit a wide range of biological properties, including anticancer, antimicrobial, anti-inflammatory and immunosuppressive activities. Their promising biological profile and easy synthetic accessibility have triggered investigations directed at the design and development of new imidazothiazole–chalcone conjugate derivatives as potential chemotherapeutics. Areas covered: The present review focuses on recent reports of the syntheses and anticancer properties of various imidazothiazoles, chalcones and imidazothiazole-linked chalcone conjugates. Furthermore, the authors discuss the structure–activity relationships...
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synthesis of imidazothiazole chalcone derivatives as anticancer and apoptosis inducing agents
ChemMedChem, 2010Co-Authors: Ahmed Kamal, Janaki M Ramaiah, Surendranadha J Reddy, Vijaya E Bharathi, Chatla Srinivas, Sreerangam N C V L Pushpavalli, D. Dastagiri, Manika PalbhadraAbstract:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI50 values ranging from −7.51 to −4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. Interestingly, these chalcone derivatives induced G0/G1-phase cell-cycle arrest, down-regulation of G1-phase cell-cycle regulatory proteins such as cyclin D1 and cyclin E1, and up-regulation of CDK4. Moreover, these compounds elicit the characteristic features of apoptosis such as enhancement in the levels of p53, p21, and p27, suppression of NF-κB, and up-regulation of caspase-9. One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies.
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synthesis of imidazothiazole chalcone derivatives as anticancer and apoptosis inducing agents
ChemMedChem, 2010Co-Authors: Ahmed Kamal, Janaki M Ramaiah, Surendranadha J Reddy, Vijaya E Bharathi, Chatla Srinivas, Sreerangam N C V L Pushpavalli, D. Dastagiri, Manika PalbhadraAbstract:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI50 values ranging from −7.51 to −4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. Interestingly, these chalcone derivatives induced G0/G1-phase cell-cycle arrest, down-regulation of G1-phase cell-cycle regulatory proteins such as cyclin D1 and cyclin E1, and up-regulation of CDK4. Moreover, these compounds elicit the characteristic features of apoptosis such as enhancement in the levels of p53, p21, and p27, suppression of NF-κB, and up-regulation of caspase-9. One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies.
Manika Palbhadra - One of the best experts on this subject based on the ideXlab platform.
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synthesis of imidazothiazole chalcone derivatives as anticancer and apoptosis inducing agents
ChemMedChem, 2010Co-Authors: Ahmed Kamal, Janaki M Ramaiah, Surendranadha J Reddy, Vijaya E Bharathi, Chatla Srinivas, Sreerangam N C V L Pushpavalli, D. Dastagiri, Manika PalbhadraAbstract:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI50 values ranging from −7.51 to −4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. Interestingly, these chalcone derivatives induced G0/G1-phase cell-cycle arrest, down-regulation of G1-phase cell-cycle regulatory proteins such as cyclin D1 and cyclin E1, and up-regulation of CDK4. Moreover, these compounds elicit the characteristic features of apoptosis such as enhancement in the levels of p53, p21, and p27, suppression of NF-κB, and up-regulation of caspase-9. One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies.
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synthesis of imidazothiazole chalcone derivatives as anticancer and apoptosis inducing agents
ChemMedChem, 2010Co-Authors: Ahmed Kamal, Janaki M Ramaiah, Surendranadha J Reddy, Vijaya E Bharathi, Chatla Srinivas, Sreerangam N C V L Pushpavalli, D. Dastagiri, Manika PalbhadraAbstract:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI50 values ranging from −7.51 to −4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. Interestingly, these chalcone derivatives induced G0/G1-phase cell-cycle arrest, down-regulation of G1-phase cell-cycle regulatory proteins such as cyclin D1 and cyclin E1, and up-regulation of CDK4. Moreover, these compounds elicit the characteristic features of apoptosis such as enhancement in the levels of p53, p21, and p27, suppression of NF-κB, and up-regulation of caspase-9. One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies.
Thomas E Johnson - One of the best experts on this subject based on the ideXlab platform.
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structure activity relationship studies of chalcone leading to 3 hydroxy 4 3 4 5 tetramethoxychalcone and its analogues as potent nuclear factor κb inhibitors and their anticancer activities
Journal of Medicinal Chemistry, 2009Co-Authors: Balasubramanian Srinivasan, Thomas E Johnson, Rahul Lad, Chengguo XingAbstract:Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-κB) activation. The structures of chalcone-based NF-κB inhibitors vary significantly that there is minimum information about their structure−activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-κB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-κB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-κB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-κB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-κB inhibitory activities, sug...
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structure activity relationship studies of chalcone leading to 3 hydroxy 4 3 4 5 tetramethoxychalcone and its analogues as potent nuclear factor κb inhibitors and their anticancer activities
Journal of Medicinal Chemistry, 2009Co-Authors: Balasubramanian Srinivasan, Thomas E Johnson, Rahul Lad, Chengguo XingAbstract:Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.