Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosq... more Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosquitoes. According to the WHO report of 2015, there were 214 million cases of malaria with 438,000 deaths worldwide. Ninety percent of world’s malaria cases occur in Africa, where the disease is recognized as a serious impediment to economic and social development. Despite advancement in malaria research, the disease continues to be a global problem, especially in developing countries. Currently, there is no effective vaccine for malaria control. In addition, although there are effective drugs for treatment of malaria, this could be lost to the drug resistance in different Plasmodium species. The most lethal form is caused by P. falciparum which has developed resistance to many chemotherapeutic agents and possibly to the current drugs of choice. Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared toward combating the disease. Covalent bi...
Background: Reducing the impact of malaria is a key to achieving the sustainable development goal... more Background: Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared towards eradicating the disease. The main objective of this study was to synthesize, determine the efficacy and safety of antiplasmodial hybrid drug comprising of sarcosine and aniline derivative for management of plasmodial infections. Results: The hybrid drug was synthesized by adding thionyl chloride to sarcosine in order to form acyl chloride which was then added to aniline to form sarcosine-aniline hybrid molecule. The IC50 of sarcosine-aniline hybrid was 44.80 ± 4.70 ng/ml compared to that of aniline derivative which was 22.86 ± 1.26 ng/ml. The IC50 of control drugs were 2.63 ± 0.38 ng/ml, 5.69 ± 0.39 ng/ml for artesunate and chloroquine respectively. There was a significant difference between IC50 of sarcosine-aniline hybrid and aniline derivative (P<0.05). There was also a significant difference between sarcosine-aniline hybrid and standard drugs used to tre...
The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of inc... more The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. The study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed 'covalent bitherapy' could improve the curative outcomes in cerebral malaria infections. Human cerebral malaria rodent model, the C57BL/6 male mice were infected intraperitoneally (ip) with Plasmodium berghei ANKA and intravenously (iv) treated with the trioxaquine from day 8 post-infection (pi) at 12.5 and 25 mg/kg, respectively, twice a day for 3 days. Treatments with the trioxaquine precursors (artesunate and 4,7-dichloroquine), and quinine were also included as controls. In vivo sa...
Malaria has continued to be a major global public health problem and a health concern in most of ... more Malaria has continued to be a major global public health problem and a health concern in most of African countries. An estimated 350–500million cases of malaria each year result in about one million deaths, mainly children under five. The rate of malaria infection is increasing rapidly partly due to drug resistance by the Plasmodium falciparum. The cost of the current
Electrochemical oxidation of alpha-allylated and alpha-benzylated N-acylated cyclic amines by usi... more Electrochemical oxidation of alpha-allylated and alpha-benzylated N-acylated cyclic amines by using a graphite anode easily affords the corresponding alpha-methoxylated products with up to 76 % yield. Ease of oxidation was affected by the type of electrode, the size of cyclic amine, and the nature of the protecting group. This method was successfully applied to the synthesis of optically active N-acylated alpha-alkyl-alpha-amino acid esters with up to 99 % ee.
Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosq... more Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosquitoes. According to the WHO report of 2015, there were 214 million cases of malaria with 438,000 deaths worldwide. Ninety percent of world’s malaria cases occur in Africa, where the disease is recognized as a serious impediment to economic and social development. Despite advancement in malaria research, the disease continues to be a global problem, especially in developing countries. Currently, there is no effective vaccine for malaria control. In addition, although there are effective drugs for treatment of malaria, this could be lost to the drug resistance in different Plasmodium species. The most lethal form is caused by P. falciparum which has developed resistance to many chemotherapeutic agents and possibly to the current drugs of choice. Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared toward combating the disease. Covalent bi...
Background: Reducing the impact of malaria is a key to achieving the sustainable development goal... more Background: Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared towards eradicating the disease. The main objective of this study was to synthesize, determine the efficacy and safety of antiplasmodial hybrid drug comprising of sarcosine and aniline derivative for management of plasmodial infections. Results: The hybrid drug was synthesized by adding thionyl chloride to sarcosine in order to form acyl chloride which was then added to aniline to form sarcosine-aniline hybrid molecule. The IC50 of sarcosine-aniline hybrid was 44.80 ± 4.70 ng/ml compared to that of aniline derivative which was 22.86 ± 1.26 ng/ml. The IC50 of control drugs were 2.63 ± 0.38 ng/ml, 5.69 ± 0.39 ng/ml for artesunate and chloroquine respectively. There was a significant difference between IC50 of sarcosine-aniline hybrid and aniline derivative (P<0.05). There was also a significant difference between sarcosine-aniline hybrid and standard drugs used to tre...
The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of inc... more The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. The study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed 'covalent bitherapy' could improve the curative outcomes in cerebral malaria infections. Human cerebral malaria rodent model, the C57BL/6 male mice were infected intraperitoneally (ip) with Plasmodium berghei ANKA and intravenously (iv) treated with the trioxaquine from day 8 post-infection (pi) at 12.5 and 25 mg/kg, respectively, twice a day for 3 days. Treatments with the trioxaquine precursors (artesunate and 4,7-dichloroquine), and quinine were also included as controls. In vivo sa...
Malaria has continued to be a major global public health problem and a health concern in most of ... more Malaria has continued to be a major global public health problem and a health concern in most of African countries. An estimated 350–500million cases of malaria each year result in about one million deaths, mainly children under five. The rate of malaria infection is increasing rapidly partly due to drug resistance by the Plasmodium falciparum. The cost of the current
Electrochemical oxidation of alpha-allylated and alpha-benzylated N-acylated cyclic amines by usi... more Electrochemical oxidation of alpha-allylated and alpha-benzylated N-acylated cyclic amines by using a graphite anode easily affords the corresponding alpha-methoxylated products with up to 76 % yield. Ease of oxidation was affected by the type of electrode, the size of cyclic amine, and the nature of the protecting group. This method was successfully applied to the synthesis of optically active N-acylated alpha-alkyl-alpha-amino acid esters with up to 99 % ee.
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