The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Radhika Guleri - One of the best experts on this subject based on the ideXlab platform.
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selective growth inhibition of human malignant melanoma cells by syringic Acid derived proteasome inhibitors
Cancer Cell International, 2013Co-Authors: Khaled Y Orabi, Mohamed Salah I Abaza, Khalid El A Sayed, Ahmed Y Elnagar, Rajaa Alattiyah, Radhika GuleriAbstract:Background: It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide Boronic Acid Derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic Acid (4-hydroxy-3,5-dimethoxybenzoic Acid, 1), a known phenolic Acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity. Methods: Using Surflex-Dock program interfaced with SYBYL, the docking affinities of syringic Acid and its proposed Derivatives to 20S proteasome were studied. Several Derivatives were virtually proposed, however, five Derivatives: benzyl 4-hydroxy-3,5-dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'-methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (5 )a nd 3',5'-dimethoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (6), were selected based on high docking scores, synthesized, and tested for their anti-mitogenic activity against human colorectal, breast and malignant melanoma cells as well as normal human fibroblast cells. Results: Derivatives 2, 5 ,a nd6 showed selective dose-dependent anti-mitogenic effect against human malignant melanoma cell lines HTB66 and HTB68 with minimal cytotoxicity on colorectal and breast cancer cells as well as normal human fibroblast cells. Derivatives 2, 5 and 6 significantly (p ≤ 0.0001) inhibited the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They growth arrested the growth of HTB66 cells at G1 and G2-phases. They also arrested the growth of HTB68 cells at S- and G2-phase, respectively. Moreover, Derivatives 2, 5 ,a nd6 markedly induced apoptosis (≥ 90%) in both HTB66 and HTB68. Conclusions: Computer-derived syringic Acid Derivatives possess selective anti-mitogenic activity on human malignant melanoma cells that may be attributed to perturbation of cell cycle, induction of apoptosis and inhibition of various 26S proteasomal activities.
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selective growth inhibition of human malignant melanoma cells by syringic Acid derived proteasome inhibitors
Cancer Cell International, 2013Co-Authors: Khaled Y Orabi, Mohamed Salah I Abaza, Khalid El A Sayed, Ahmed Y Elnagar, Rajaa Alattiyah, Radhika GuleriAbstract:Background It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide Boronic Acid Derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic Acid (4-hydroxy-3,5-dimethoxybenzoic Acid, 1), a known phenolic Acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity.
Valentino J Stella - One of the best experts on this subject based on the ideXlab platform.
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degradation pathways of a peptide Boronic Acid Derivative 2 pyz co phe leu b oh 2
Journal of Pharmaceutical Sciences, 2000Co-Authors: Wanda N Waugh, Valentino J StellaAbstract:The peptide Boronic Acid Derivative 2-Pyz-(CO)-Phe-Leu-B(OH)(2) is a potent inhibitor of 20S proteasome and a proposed anticancer agent. During preformulation studies, the compound presented erratic stability behavior. Efforts were made to isolate and identify the degradation products, thereby helping to identify possible mechanisms for the degradation. The reaction of 2-Pyz-(CO)-Phe-Leu-B(OH)(2) with hydrogen peroxide not only provided a convenient way to isolate the initial degradation products seen from hydrolysis in aqueous buffers but also showed that the major, initial degradation pathway was probably oxidative in nature. The isolated degradation products were characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, and optical rotation dispersion. In the presence of hydrogen peroxide, the Boronic Acid group was cleaved from 2-Pyz-(CO)-Phe-Leu-B(OH)(2) to give an alcohol with an apparent retention of the original stereochemistry. Subsequent isomerization and further hydrolysis were then seen. Surprisingly, added ascorbate and EDTA accelerated rather than inhibited degradation. Degradation of 2-Pyz-(CO)-Phe-Leu-B(OH)(2) under Acidic and basic conditions seemed to be mediated by an initial oxidative degradation pathway similar to that seen with the peroxide.
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degradation pathways of a peptide Boronic Acid Derivative 2 pyz co phe leu b oh 2
Journal of Pharmaceutical Sciences, 2000Co-Authors: Sara Wu, Wanda N Waugh, Valentino J StellaAbstract:Abstract The peptide Boronic Acid Derivative 2‐Pyz‐(CO)‐Phe‐Leu‐B(OH) 2 is a potent inhibitor of 20S proteasome and a proposed anticancer agent. During preformulation studies, the compound presented erratic stability behavior. Efforts were made to isolate and identify the degradation products, thereby helping to identify possible mechanisms for the degradation. The reaction of 2‐Pyz‐(CO)‐Phe‐Leu‐B(OH) 2 with hydrogen peroxide not only provided a convenient way to isolate the initial degradation products seen from hydrolysis in aqueous buffers but also showed that the major, initial degradation pathway was probably oxidative in nature. The isolated degradation products were characterized by nuclear magnetic resonance spectroscopy, mass spectrometry, and optical rotation dispersion. In the presence of hydrogen peroxide, the Boronic Acid group was cleaved from 2‐Pyz‐(CO)‐Phe‐Leu‐B(OH) 2 to give an alcohol with an apparent retention of the original stereochemistry. Subsequent isomerization and further hydrolysis were then seen. Surprisingly, added ascorbate and EDTA accelerated rather than inhibited degradation. Degradation of 2‐Pyz‐(CO)‐Phe‐Leu‐B(OH) 2 under Acidic and basic conditions seemed to be mediated by an initial oxidative degradation pathway similar to that seen with the peroxide. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 758–765, 2000
Khaled Y Orabi - One of the best experts on this subject based on the ideXlab platform.
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selective growth inhibition of human malignant melanoma cells by syringic Acid derived proteasome inhibitors
Cancer Cell International, 2013Co-Authors: Khaled Y Orabi, Mohamed Salah I Abaza, Khalid El A Sayed, Ahmed Y Elnagar, Rajaa Alattiyah, Radhika GuleriAbstract:Background: It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide Boronic Acid Derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic Acid (4-hydroxy-3,5-dimethoxybenzoic Acid, 1), a known phenolic Acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity. Methods: Using Surflex-Dock program interfaced with SYBYL, the docking affinities of syringic Acid and its proposed Derivatives to 20S proteasome were studied. Several Derivatives were virtually proposed, however, five Derivatives: benzyl 4-hydroxy-3,5-dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'-methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (5 )a nd 3',5'-dimethoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (6), were selected based on high docking scores, synthesized, and tested for their anti-mitogenic activity against human colorectal, breast and malignant melanoma cells as well as normal human fibroblast cells. Results: Derivatives 2, 5 ,a nd6 showed selective dose-dependent anti-mitogenic effect against human malignant melanoma cell lines HTB66 and HTB68 with minimal cytotoxicity on colorectal and breast cancer cells as well as normal human fibroblast cells. Derivatives 2, 5 and 6 significantly (p ≤ 0.0001) inhibited the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They growth arrested the growth of HTB66 cells at G1 and G2-phases. They also arrested the growth of HTB68 cells at S- and G2-phase, respectively. Moreover, Derivatives 2, 5 ,a nd6 markedly induced apoptosis (≥ 90%) in both HTB66 and HTB68. Conclusions: Computer-derived syringic Acid Derivatives possess selective anti-mitogenic activity on human malignant melanoma cells that may be attributed to perturbation of cell cycle, induction of apoptosis and inhibition of various 26S proteasomal activities.
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selective growth inhibition of human malignant melanoma cells by syringic Acid derived proteasome inhibitors
Cancer Cell International, 2013Co-Authors: Khaled Y Orabi, Mohamed Salah I Abaza, Khalid El A Sayed, Ahmed Y Elnagar, Rajaa Alattiyah, Radhika GuleriAbstract:Background It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide Boronic Acid Derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic Acid (4-hydroxy-3,5-dimethoxybenzoic Acid, 1), a known phenolic Acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity.
Parthasarathi Dastidar - One of the best experts on this subject based on the ideXlab platform.
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supramolecular hydrogel derived from a c3 symmetric Boronic Acid Derivative for stimuli responsive release of insulin and doxorubicin
Langmuir, 2018Co-Authors: Koushik Sarkar, Parthasarathi DastidarAbstract:A C3-symmetric triazine based triBoronic Acid (HG1) was designed and synthesized. HG1 was found to give hydrogel in DMSO–water (1:9). The hydrogel was rheo-reversible and thermoreversible over a few cycles. Single-crystal X-ray diffraction (SXRD) studies on the crystals of HG1 established the presence of honeycomb network in which solvent molecules (DMSO and water) were occluded. SXRD data corroborated well with the hypothesis based on which HG1 was designed. Stimuli responsive release (in vitro) of insulin and doxorubicin from the hydrogel was also achieved.
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Correction to “Supramolecular Hydrogel Derived from a C3‑Symmetric Boronic Acid Derivative for Stimuli Responsive Release of Insulin and Doxorubicin”
2018Co-Authors: Koushik Sarkar, Parthasarathi DastidarAbstract:Correction to “Supramolecular Hydrogel Derived from a C3‑Symmetric Boronic Acid Derivative for Stimuli Responsive Release of Insulin and Doxorubicin
Ahmed Y Elnagar - One of the best experts on this subject based on the ideXlab platform.
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selective growth inhibition of human malignant melanoma cells by syringic Acid derived proteasome inhibitors
Cancer Cell International, 2013Co-Authors: Khaled Y Orabi, Mohamed Salah I Abaza, Khalid El A Sayed, Ahmed Y Elnagar, Rajaa Alattiyah, Radhika GuleriAbstract:Background: It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide Boronic Acid Derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic Acid (4-hydroxy-3,5-dimethoxybenzoic Acid, 1), a known phenolic Acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity. Methods: Using Surflex-Dock program interfaced with SYBYL, the docking affinities of syringic Acid and its proposed Derivatives to 20S proteasome were studied. Several Derivatives were virtually proposed, however, five Derivatives: benzyl 4-hydroxy-3,5-dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'-methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (5 )a nd 3',5'-dimethoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (6), were selected based on high docking scores, synthesized, and tested for their anti-mitogenic activity against human colorectal, breast and malignant melanoma cells as well as normal human fibroblast cells. Results: Derivatives 2, 5 ,a nd6 showed selective dose-dependent anti-mitogenic effect against human malignant melanoma cell lines HTB66 and HTB68 with minimal cytotoxicity on colorectal and breast cancer cells as well as normal human fibroblast cells. Derivatives 2, 5 and 6 significantly (p ≤ 0.0001) inhibited the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They growth arrested the growth of HTB66 cells at G1 and G2-phases. They also arrested the growth of HTB68 cells at S- and G2-phase, respectively. Moreover, Derivatives 2, 5 ,a nd6 markedly induced apoptosis (≥ 90%) in both HTB66 and HTB68. Conclusions: Computer-derived syringic Acid Derivatives possess selective anti-mitogenic activity on human malignant melanoma cells that may be attributed to perturbation of cell cycle, induction of apoptosis and inhibition of various 26S proteasomal activities.
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selective growth inhibition of human malignant melanoma cells by syringic Acid derived proteasome inhibitors
Cancer Cell International, 2013Co-Authors: Khaled Y Orabi, Mohamed Salah I Abaza, Khalid El A Sayed, Ahmed Y Elnagar, Rajaa Alattiyah, Radhika GuleriAbstract:Background It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide Boronic Acid Derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic Acid (4-hydroxy-3,5-dimethoxybenzoic Acid, 1), a known phenolic Acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity.