The currently available antimitotic drugs directly target the microtubule building blocks. These ... more The currently available antimitotic drugs directly target the microtubule building blocks. These drugs induce adverse side-effects including neurotoxicity, and cancer cells can potentially develop resistance to them. New antimitotic drugs act indirectly on microtubules, these drugs have specifi c functions on phases of mitosis, and their inhibition may produce fewer side-effects than tubulin drugs. Eg5 motors are a member of the kinesin family which are required for spindle bipolarity maintenance. Inhibition of these motors induces mono-asters cells. S-trityl-L-cysteine (STLC) is a specifi c and effective Eg5 inhibitor, the trityl group of the STLC binds to three hydrophobic sites inside the binding pocket [1]. Our aim is to design and synthesise high potency specific Eg5 inhibitors which have a higher inhibition activity than the STLC. Our suggested compounds have in general extended benzyl group, which is believed to be more fl exible compared to the phenyl group of the STLC. It i...
ABSTRACT The decomposition behaviour of chlorogenic acid (CGA) was studied under inert (nitrogen)... more ABSTRACT The decomposition behaviour of chlorogenic acid (CGA) was studied under inert (nitrogen) and oxidative (air) atmospheres by themogravimetric analysis (TGA). Thermal decomposition was found to be faster under an air atmosphere with a total weight change of 97 ± 1% compared to 61 ± 1% under a nitrogen atmosphere. At least 3 or 4 processes were observed for decomposition under air and nitrogen atmospheres, respectively. Furthermore, the 1st process, which follows a melt-crystallisation, was found not to be influenced by the different atmospheric conditions. Peak fitting of the CGA decomposition profile, in the form of a derivative thermogram (DTG), under a nitrogen atmosphere, revealed the presence of five complete decomposition processes and the first half of a sixth process between 160 and 500 °C. A comparison is made between the peak fitting and dynamic High-Res™ TGA experiments to demonstrate the reliability of the peak fitting approach. The predictions were then converted into discrete thermogravimetric (TG) curves with a single-step weight change. Since this approach provides baseline separation between overlapping processes, it has been possible to reliably determine the fractional weight change and the activation energy dependence on the reaction progression for the discrete TGA decomposition processes. The fractional weight change associated with processes 1–5 is: 5.3 ± 0.7, 2.0 ± 0.4, 16.4 ± 0.9, 30.9 ± 1.6 and 5.5 ± 0.5%. Catechol was found to be the major decomposition product. The average activation energies of the 5 processes were calculated to be 176 ± 34, 185 ± 4, 223 ± 19, 245 ± 47, 295 ± 80 kJ/mol when an integral method (Kissinger–Akahiro–Sunose) is used and 120 ± 25, 169 ± 18, 191 ± 12, 284 ± 64, 245 ± 46 kJ/mol when a differential method (Friedman) is used for processes 1–5, respectively
Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In ... more Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.
The currently available antimitotic drugs directly target the microtubule building blocks. These ... more The currently available antimitotic drugs directly target the microtubule building blocks. These drugs induce adverse side-effects including neurotoxicity, and cancer cells can potentially develop resistance to them. New antimitotic drugs act indirectly on microtubules, these drugs have specifi c functions on phases of mitosis, and their inhibition may produce fewer side-effects than tubulin drugs. Eg5 motors are a member of the kinesin family which are required for spindle bipolarity maintenance. Inhibition of these motors induces mono-asters cells. S-trityl-L-cysteine (STLC) is a specifi c and effective Eg5 inhibitor, the trityl group of the STLC binds to three hydrophobic sites inside the binding pocket [1]. Our aim is to design and synthesise high potency specific Eg5 inhibitors which have a higher inhibition activity than the STLC. Our suggested compounds have in general extended benzyl group, which is believed to be more fl exible compared to the phenyl group of the STLC. It i...
ABSTRACT The decomposition behaviour of chlorogenic acid (CGA) was studied under inert (nitrogen)... more ABSTRACT The decomposition behaviour of chlorogenic acid (CGA) was studied under inert (nitrogen) and oxidative (air) atmospheres by themogravimetric analysis (TGA). Thermal decomposition was found to be faster under an air atmosphere with a total weight change of 97 ± 1% compared to 61 ± 1% under a nitrogen atmosphere. At least 3 or 4 processes were observed for decomposition under air and nitrogen atmospheres, respectively. Furthermore, the 1st process, which follows a melt-crystallisation, was found not to be influenced by the different atmospheric conditions. Peak fitting of the CGA decomposition profile, in the form of a derivative thermogram (DTG), under a nitrogen atmosphere, revealed the presence of five complete decomposition processes and the first half of a sixth process between 160 and 500 °C. A comparison is made between the peak fitting and dynamic High-Res™ TGA experiments to demonstrate the reliability of the peak fitting approach. The predictions were then converted into discrete thermogravimetric (TG) curves with a single-step weight change. Since this approach provides baseline separation between overlapping processes, it has been possible to reliably determine the fractional weight change and the activation energy dependence on the reaction progression for the discrete TGA decomposition processes. The fractional weight change associated with processes 1–5 is: 5.3 ± 0.7, 2.0 ± 0.4, 16.4 ± 0.9, 30.9 ± 1.6 and 5.5 ± 0.5%. Catechol was found to be the major decomposition product. The average activation energies of the 5 processes were calculated to be 176 ± 34, 185 ± 4, 223 ± 19, 245 ± 47, 295 ± 80 kJ/mol when an integral method (Kissinger–Akahiro–Sunose) is used and 120 ± 25, 169 ± 18, 191 ± 12, 284 ± 64, 245 ± 46 kJ/mol when a differential method (Friedman) is used for processes 1–5, respectively
Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In ... more Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.
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Papers by Samuel Owusu-ware