Background: Aspergillus fumigatus is the most common causative agent of invasive fungal infection... more Background: Aspergillus fumigatus is the most common causative agent of invasive fungal infection in immunosuppressed individuals. These include patients receiving immunosuppressive therapy for autoimmune or neoplastic disease, organ transplant recipients, and AIDS patients. A. fumigatus is the primary cause of invasive infection in the lungs and represents a major cause of morbidity and mortality in infected individuals. Additionally, A. fumigatus can cause chronic pulmonary infections, allergic bronchopulmonary aspergillosis, or allergic disease in immunocompetent hosts. Falcarindiol is a polyacetylene found in carrot roots which has antifungal activity.
Structure-activity relationship (SAR) is a method used in the detection of the chemical and biolo... more Structure-activity relationship (SAR) is a method used in the detection of the chemical and biological activity relationship of compounds. This concept therefore points to the link between the chemical structures and biological and the biological activities of compounds, which also includes the toxicity. Production of new drugs with a higher potency and limited side effects, but having structural similarity with the original drug is another application of SAR theory. The essence of the structure-activity relationships also cuts across the toxicological studies on a compound. The design of commercial chemicals with specific wanted properties for long has involved the use of SARs. The importance also includes the prediction of therapeutic activities and pharmacological properties in drug design processes. Where the biological activity is quantified, quantitative structure-activity relationship (QSAR) is defined. Chemical structures and biological activities take advantage of the QSAR to build a mathematical relationship where a reliable measure depends solely on chemicals descriptors and their activities. SAR aims to identify which functional groups are important for activity, thus, employs few methods to aid in its activity, including: alter, remove or mask a functional group and test the analogue for activity. There are numbers of chemical and biological molecules to which SAR is applicable, however, a common area of application is with the drugs. Understanding the mechanism of action of a particular drug is pertinent to effectively employing SAR. The known mechanism of drugs depends on their active sites. Drugs can act on enzymes either by activating or inhibiting them via competitive inhibition or by non-competitive inhibition. Artemisinins has been seen to be a good example for this process. Artemisinins are currently available as important antimalarial class of drugs, because of their effectiveness against resistant strains of the malarial parasites. Structure-activity relationship is therefore made obvious and practically applicable in this class of drug.
— Background: Malaria is a major global public health challenge. Plasmodium falciparum happens to... more — Background: Malaria is a major global public health challenge. Plasmodium falciparum happens to be the most virulent among the causative parasites of malaria. The development of drug resistance in Plasmodium falciparum strains has built up a great interest in the search for new antimalarial drugs and drug targets. As part of a program to develop metabolic enzymes as potential drug targets, the 3-dimensional structure of Plasmodium falciparum triosephosphate isomerase was determined. The focus on glycolytic and electron transport chain enzymes in the malaria parasite results from the observation that in the asexual stage of the parasite in the human red blood cells, the energy requirements of the organism are almost exclusively met by glycolysis and the electron transport chain enzyme of the parasite remains highly stable and resistant. Materials and Methods: The amino acid sequences of the experimental enzymes were mined from the NCBI database and sequence aligment between the triosephosphate isomerase and cytochrome oxidase of P. falciparum and their respective human orthologs were performed using the ClustalW sequence alignment software. The alignments were visualized using the Bioedit software which is a biological sequence alignment editor. The MEGA7 software was used to view and highlight the protein conserved domains and variable sites while the prediction of the protein domain was done using the PSIPRED. The amino acid composition graph of the P. falciparum enzymes was also plotted using specific functions on the MEGA7 software. Results: Here, we present a computational analysis of the amino acid composition of Plasmodium falciparum triosephosphate isomerase and cytochrome oxidase which are cytosolic and mitochondrial enzymes respectively. An alignment was also carried out with the human orthologs of each of the respective analysed parasite enzyme sequence. This comparison with the human enzymes was used to predict their functional similarity in respect to therapeutic drug design and the predicted potency of the drug for prophylaxis and disease treatment. Conclusions: Antimalarial drugs targeted at the Plasmodium falciparum triosephosphate isomerase tends to act faster compared to the mitochondrial cytochrome oxidase drug target counterparts. The initial takes advantage on the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzymes.
Background: Pneumonia is the second most common nosocomial infection. The most common cause of no... more Background: Pneumonia is the second most common nosocomial infection. The most common cause of nosocomial pneumonia is microaspiration of etiological agents that includes gram-positive bacteria such as Streptococcus pneumoniae. 6-Gingerol is isolated from the rhizomes or roots of the plant Zingiber officinale (ginger). Ginger has been widely used in the global herbal medicinal practices since ancient times for a wide array of ailments including dementia, fever, infectious diseases and helminthiasis.
— Background: Bronchial asthma is an inflammatory disease of the airways which may be worsened du... more — Background: Bronchial asthma is an inflammatory disease of the airways which may be worsened due to numerous extrinsic factors. The most common trigger is continuous exposure to allergens of which fungal agents are important factors. There is overwhelming evidence for the presence of fungal sensitization in patients with asthma. It has been proposed that fungal lipoxygenase enzymes and their eicosanoid products are crucial in asthmatic diseases. Human 5-lipoxygenase derived leukotrienes induce inflammation, mucus secretion, vasodilation, and bronchial constriction. Research has also shown that the fungal pathogen Aspergillus fumigatus is capable of secreting LoxB which is a 5-lipoxygenase homolog and it participates in eicosanoid production, including leukotrienes. LoxB is translocated into the lung epithelial cells where it participates in the production of leukotrienes and other eicosanoids, and induces asthmatic responses, such as bronchoconstriction. Analysis from this study gives an idea of facts needed in the structure-based drug design geared towards tackling this disease and this design relies solely on the knowledge of the three-dimensional structure of the biomolecular target which is the lipoxygenase enzyme. Results: In this report, we present a computational analysis of the nucleotide and amino acid composition of lipoxygenase obtained from Aspergillus fumigatus. This in turn was used in the protein secondary and 3D homology modelling necessary for a structure based drug design. The enzyme sensitivity to antifungal drugs was also predicted using results obtained from the protein disordered region analysis. Conclusions: Antifungal drugs designed specifically to target the fungal lipoxygenase tend to act fast based on the enzyme instability. These drugs take advantage of the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzyme.
Background: Aspergillus fumigatus is the most common causative agent of invasive fungal infection... more Background: Aspergillus fumigatus is the most common causative agent of invasive fungal infection in immunosuppressed individuals. These include patients receiving immunosuppressive therapy for autoimmune or neoplastic disease, organ transplant recipients, and AIDS patients. A. fumigatus is the primary cause of invasive infection in the lungs and represents a major cause of morbidity and mortality in infected individuals. Additionally, A. fumigatus can cause chronic pulmonary infections, allergic bronchopulmonary aspergillosis, or allergic disease in immunocompetent hosts. Falcarindiol is a polyacetylene found in carrot roots which has antifungal activity.
Structure-activity relationship (SAR) is a method used in the detection of the chemical and biolo... more Structure-activity relationship (SAR) is a method used in the detection of the chemical and biological activity relationship of compounds. This concept therefore points to the link between the chemical structures and biological and the biological activities of compounds, which also includes the toxicity. Production of new drugs with a higher potency and limited side effects, but having structural similarity with the original drug is another application of SAR theory. The essence of the structure-activity relationships also cuts across the toxicological studies on a compound. The design of commercial chemicals with specific wanted properties for long has involved the use of SARs. The importance also includes the prediction of therapeutic activities and pharmacological properties in drug design processes. Where the biological activity is quantified, quantitative structure-activity relationship (QSAR) is defined. Chemical structures and biological activities take advantage of the QSAR to build a mathematical relationship where a reliable measure depends solely on chemicals descriptors and their activities. SAR aims to identify which functional groups are important for activity, thus, employs few methods to aid in its activity, including: alter, remove or mask a functional group and test the analogue for activity. There are numbers of chemical and biological molecules to which SAR is applicable, however, a common area of application is with the drugs. Understanding the mechanism of action of a particular drug is pertinent to effectively employing SAR. The known mechanism of drugs depends on their active sites. Drugs can act on enzymes either by activating or inhibiting them via competitive inhibition or by non-competitive inhibition. Artemisinins has been seen to be a good example for this process. Artemisinins are currently available as important antimalarial class of drugs, because of their effectiveness against resistant strains of the malarial parasites. Structure-activity relationship is therefore made obvious and practically applicable in this class of drug.
— Background: Malaria is a major global public health challenge. Plasmodium falciparum happens to... more — Background: Malaria is a major global public health challenge. Plasmodium falciparum happens to be the most virulent among the causative parasites of malaria. The development of drug resistance in Plasmodium falciparum strains has built up a great interest in the search for new antimalarial drugs and drug targets. As part of a program to develop metabolic enzymes as potential drug targets, the 3-dimensional structure of Plasmodium falciparum triosephosphate isomerase was determined. The focus on glycolytic and electron transport chain enzymes in the malaria parasite results from the observation that in the asexual stage of the parasite in the human red blood cells, the energy requirements of the organism are almost exclusively met by glycolysis and the electron transport chain enzyme of the parasite remains highly stable and resistant. Materials and Methods: The amino acid sequences of the experimental enzymes were mined from the NCBI database and sequence aligment between the triosephosphate isomerase and cytochrome oxidase of P. falciparum and their respective human orthologs were performed using the ClustalW sequence alignment software. The alignments were visualized using the Bioedit software which is a biological sequence alignment editor. The MEGA7 software was used to view and highlight the protein conserved domains and variable sites while the prediction of the protein domain was done using the PSIPRED. The amino acid composition graph of the P. falciparum enzymes was also plotted using specific functions on the MEGA7 software. Results: Here, we present a computational analysis of the amino acid composition of Plasmodium falciparum triosephosphate isomerase and cytochrome oxidase which are cytosolic and mitochondrial enzymes respectively. An alignment was also carried out with the human orthologs of each of the respective analysed parasite enzyme sequence. This comparison with the human enzymes was used to predict their functional similarity in respect to therapeutic drug design and the predicted potency of the drug for prophylaxis and disease treatment. Conclusions: Antimalarial drugs targeted at the Plasmodium falciparum triosephosphate isomerase tends to act faster compared to the mitochondrial cytochrome oxidase drug target counterparts. The initial takes advantage on the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzymes.
Background: Pneumonia is the second most common nosocomial infection. The most common cause of no... more Background: Pneumonia is the second most common nosocomial infection. The most common cause of nosocomial pneumonia is microaspiration of etiological agents that includes gram-positive bacteria such as Streptococcus pneumoniae. 6-Gingerol is isolated from the rhizomes or roots of the plant Zingiber officinale (ginger). Ginger has been widely used in the global herbal medicinal practices since ancient times for a wide array of ailments including dementia, fever, infectious diseases and helminthiasis.
— Background: Bronchial asthma is an inflammatory disease of the airways which may be worsened du... more — Background: Bronchial asthma is an inflammatory disease of the airways which may be worsened due to numerous extrinsic factors. The most common trigger is continuous exposure to allergens of which fungal agents are important factors. There is overwhelming evidence for the presence of fungal sensitization in patients with asthma. It has been proposed that fungal lipoxygenase enzymes and their eicosanoid products are crucial in asthmatic diseases. Human 5-lipoxygenase derived leukotrienes induce inflammation, mucus secretion, vasodilation, and bronchial constriction. Research has also shown that the fungal pathogen Aspergillus fumigatus is capable of secreting LoxB which is a 5-lipoxygenase homolog and it participates in eicosanoid production, including leukotrienes. LoxB is translocated into the lung epithelial cells where it participates in the production of leukotrienes and other eicosanoids, and induces asthmatic responses, such as bronchoconstriction. Analysis from this study gives an idea of facts needed in the structure-based drug design geared towards tackling this disease and this design relies solely on the knowledge of the three-dimensional structure of the biomolecular target which is the lipoxygenase enzyme. Results: In this report, we present a computational analysis of the nucleotide and amino acid composition of lipoxygenase obtained from Aspergillus fumigatus. This in turn was used in the protein secondary and 3D homology modelling necessary for a structure based drug design. The enzyme sensitivity to antifungal drugs was also predicted using results obtained from the protein disordered region analysis. Conclusions: Antifungal drugs designed specifically to target the fungal lipoxygenase tend to act fast based on the enzyme instability. These drugs take advantage of the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzyme.
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