P. Kirira - Academia.edu (original) (raw)

Papers by P. Kirira

Research paper thumbnail of The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya

Journal of Ethnopharmacology, 2008

Research paper thumbnail of Antimalarial activity of some plants traditionally used in treatment of malaria in Kwale district of Kenya

Journal of Ethnopharmacology, 2007

their cytotoxic effects. The most active extracts (IC(50)<10 microg/ml) screened against chloroqu... more their cytotoxic effects. The most active extracts (IC(50)<10 microg/ml) screened against chloroquine (CQ) sensitive (D6) and resistant (W2) P. falciparum clones, were the water and methanol extracts of Maytenus undata (Thunb.) Blakelock (Celasteraceae), methanol extracts of Flueggea virosa (Willd.) Voigt (Euphorbiaceae), Maytenus putterlickioides (Loes.) Excell and Mendoca (Celastraceae), and Warburgia stuhlmannii Engl. (Canellaceae). These extracts showed various cytotoxic levels on Vero E6 cells with the water extract of M. undata exhibiting least cytotoxicity. At least one of the extracts of the plant species exhibited a high chemo suppression of parasitaemia >70% in a murine model of P. berghei infected mice. These results indicate that there is potential for isolation of a lead compound from the extracts of the five plants. W. stuhlmannii and M. putterlickioides have not been reported before for antiplasmodial activity.

Research paper thumbnail of Determining the Prevalence and Risk Factors Associated with Leishmaniasis among Residents of Rural Marigat Sub-County, Baringo County- Kenya

Current Overview on Disease and Health Research Vol. 1

Research paper thumbnail of Chemical Synthesis, Efficacy, and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds

Journal of Tropical Medicine

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...

Research paper thumbnail of Chemical Synthesis, Efficacy and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds

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...

Research paper thumbnail of Quality of Water and the Recovery Time of Malnourished Children Enrolled In a Nutritional Feeding Programme: Lessons from Parkishon Region, Marsabit County, Kenya

Archives of Clinical and Medical Case Reports

Objective: Malnutrition is a problem that continues to plague children from resource scarce regio... more Objective: Malnutrition is a problem that continues to plague children from resource scarce regions of Kenya. To address this health challenge, the government of Kenya initiated feeding programmes aimed at improving the daily nutritional food intake of underweight and sickly children from these regions. This study examined the relationship between the quality of water and the children's recovery as measured by the Mid-Upper Arm Circumference (MUAC) in Parkishon region of Kenya. Methods: The study followed 82 underweight children on a PlumpNut diet. Thirty seven (37) children were using water from a water backpack while the other children were using water from Silanga, a dam that is the only source of water in the region. The recovery time of the children was measured using the MUAC index. Results: Of the 37 children enrolled in the nutritional feeding programme and from families that received the water backpack, 10 recovered fully within three months and were put off the nutritional supplement program. The underweight children in the same nutritional feeding programme but whose families did not receive the water backpack, and therefore continued to consume water from the dam, are yet to recover and are still enrolled in the nutritional feeding programme.

Research paper thumbnail of Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model

Malaria journal, Jul 3, 2017

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...

Research paper thumbnail of In Situ Preparation of Chiral Bifunctional Catalysts and Their Application to Asymmetric Michael Addition Reactions

Asian Journal of Organic Chemistry, 2012

Research paper thumbnail of ChemInform Abstract: Diastereoselective Arylation of Enantiopure 3-Bromopiperidin-2-one Derived from (R)-(-)-2-Phenylglycinol with Organocuprate Reagents

ChemInform, 2012

Diastereoselective Arylation of Enantiopure 3-Bromopiperidin-2-one Derived from (R)-(-)-2-Phenylg... more Diastereoselective Arylation of Enantiopure 3-Bromopiperidin-2-one Derived from (R)-(-)-2-Phenylglycinol with Organocuprate Reagents.-The 3-bromolactam (I) derived from (R)-2-phenylglycinol undergoes a stereoselective reaction with arylcuprate reagents.-(ROMERO, O.;

Research paper thumbnail of Diastereoselective arylation of l-proline derivatives at the 5-position

Tetrahedron, 2008

Diastereoselective introduction of nucleophiles into L-proline derivatives at the 5-position was ... more Diastereoselective introduction of nucleophiles into L-proline derivatives at the 5-position was achieved with suitable selection of N-protecting group. N-Methoxycarbonylated or benzyloxycarbonylated L-proline derivatives reacted with arene to give cis-arylated products. On the other hand, N-benzoylated L-proline derivative preferentially gave trans-arylated product which could be easily transformed into optically active C 2-symmetrical pyrrolidine derivative. Such derivative 5, worked well as an organic activator in the asymmetric reduction of aromatic imines by Cl 3 SiH.

Research paper thumbnail of Antiplasmodial and cytotoxicity activities of some selected plants used by the Maasai community, Kenya

South African Journal of Botany, 2011

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

Research paper thumbnail of Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy

Current Medicinal Chemistry, 2011

Efforts to develop an effective malaria vaccine are yet to be successful and thus chemotherapy re... more Efforts to develop an effective malaria vaccine are yet to be successful and thus chemotherapy remains the mainstay of malaria control strategy. Plasmodium falciparum, the parasite that causes about 90% of all global malaria cases is increasingly becoming resistant to most antimalarial drugs in clinical use. This dire situation is aggravated by reports from Southeast Asia, of the parasite becoming resistant to the "magic bullet" artemisinins, the last line of defense in malaria chemotherapy. Drug development is a laborious and time consuming process, and thus antimalarial drug discovery approaches currently being deployed largely include optimization of therapy with available drugs-including combination therapy and developing analogues of the existing drugs. However, the latter strategy may be hampered by crossresistance, since agents that are closely related chemically may share similar mechanisms of action and/or targets. This may render new drugs ineffective even before they are brought to clinical use. Evaluation of drug-resistance reversers (chemosensitizers) against quinoline-based drugs such as chloroquine and mefloquine is another approach that is being explored. Recently, evaluation of new chemotherapeutic targets is gaining new impetus as knowledge of malaria parasite biology expands. Also, single but hybrid molecules with dual functionality and/or targets have been developed through rational drug design approach, termed as "covalent bitherapy". Since desperate times call for radical measures, this review aims to explore novel rational drug-design strategies potentially capable of revolutionizing malaria therapy. We thus explore malaria apoptosis machinery as a novel drug target, and also discuss the potential of hybrid molecules as well as prodrugs and double prodrugs in malaria chemotherapy.

Research paper thumbnail of Electrochemical Deallylation of α-Allyl Cyclic Amines and Synthesis of Optically Active Quaternary Cyclic Amino Acids

Chemistry - A European Journal, 2010

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.

Research paper thumbnail of Tigliane Diterpenoids from the Stem Bark of Neoboutonia macrocalyx

Neoboutonia macrocalyx is a plant used by traditional healers among the Meru community in Kenya. ... more Neoboutonia macrocalyx is a plant used by traditional healers among the Meru community in Kenya. Chromatographic fractionation of the petroleum ether and dichloromethane extracts of this plant yielded one known (1) and three new tigliane-type diterpenoids (2-4). The chemical structures of the isolated compounds were established through spectroscopic data interpretation.

Research paper thumbnail of Anti-plasmodial activity of the extracts of some Kenyan medicinal plants

Journal of Ethnopharmacology, 2009

Ethnopharmacological relevance: The spread of drug resistant Plasmodium falciparum strains necess... more Ethnopharmacological relevance: The spread of drug resistant Plasmodium falciparum strains necessitates search for alternative newer drugs for use against malaria. Medicinal plants used traditionally in preparation of herbal medicines for malaria are potential source of new anti-malarial drugs. Aim of the Study: To identify the anti-plasmodial potential of twelve plants used in preparing herbal remedies for malaria in Kilifi and Tharaka districts of Kenya. Materials and Methods: Twelve plants used traditionally for anti-malarial therapy in Kilifi and Tharaka districts were extracted with water/methanol yielding twenty-three extracts. The extracts were tested against chloroquine sensitive (NF54) and resistant (ENT30) P. falciparum strains in vitro using 3 Hypoxanthine assay. Results: Seven (30%) extracts showed activity against P. falciparum with IC 50 values below 20 g/ml. The remaining 16 extracts showed low or no activity. The most active extracts were from Zanthoxylum chalybeum (Rutaceae) with an IC 50 value of 3.65 g/ml, Cyperus articulatus (Cyperaceae) with 4.84 g/ml, and Cissampelos pareira (Menispermaceae) with 5.85 g/ml. Conclusions: This study revealed plants, that are potential sources of anti-malarial compounds. Antiplasmodial activities of extracts of T. simplicifolia, C. pareira, and C. articulatus are reported for the first time.

Research paper thumbnail of Antimalarial activity of some plants traditionally used in treatment of malaria in Kwale district of Kenya

Journal of Ethnopharmacology, 2007

Developing countries, where malaria is endemic, depend strongly on traditional medicine as a sour... more Developing countries, where malaria is endemic, depend strongly on traditional medicine as a source for inexpensive treatment of this disease. However, scientific data to validate the antimalarial properties of these herbal remedies are scarce. Consequently, it is important that antimalarial medicinal plants are investigated, in order to establish their efficacy and to determine their potential as sources of new antimalarial drugs. In this study, we evaluated the claimed antimalarial properties of fifty eight crude extracts from fifteen plants used in traditional medicine against malaria and fever, mainly from Southern African regions. The air-dried powdered plant parts (roots, leaves, seeds or bark) or whole plants were extracted, sequentially, with solvents of increased polarity (n-hexane, dichloromethane, ethyl acetate and methanol). Schizontocidal activity was measured using a standard in vitro assay, with 3D7 Plasmodium falciparum strain. From the 58 extracts tested, two of them showed a significant activity (IC 50 < 5 µg/mL), and 34.5 % showed a moderate activity (10 < IC 50 < 50 µg/mL). A bioassay-guided fractionation of the most active extracts is ongoing.

Research paper thumbnail of Anti-plasmodial activity and toxicity of extracts of plants used in traditional malaria therapy in Meru and Kilifi Districts of Kenya

Journal of Ethnopharmacology, 2006

The methanol and aqueous extracts of 10 plant species (Acacia nilotica, Azadirachta indica, Caris... more The methanol and aqueous extracts of 10 plant species (Acacia nilotica, Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii, Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro anti-plasmodial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of the methanol extracts were toxic to the brine shrimp (LD 50 < 100 g/ml), while 50% showed in vitro anti-plasmodial activity (IC 50 < 100 g/ml). The methanol extract of the stem bark of N. macrocalyx had the highest toxicity to brine shrimp nauplii (LD 50 21.04 ± 1.8 g/ml). Methanol extracts of the rest of the plants exhibited mild or no brine shrimp toxicity (LD 50 > 50 g/ml). The aqueous extracts of N. macrocalyx had mild brine shrimp toxicity (LD 50 41.69 ± 0.9 g/ml), while the rest were lower (LD 50 > 100 g/ml). The methanol extracts of F. angolensis and Zanthoxylum usambarense had IC 50 values <6 g/ml while the aqueous ones had values between 6 and 15 g/ml, against both chloroquine-sensitive and resistant P. falciparum strains. The results support the use of traditional herbs for anti-malarial therapy and demonstrate their potential as sources of drugs.

Research paper thumbnail of Anti-parasitic activity and cytotoxicity of selected medicinal plants from Kenya

Journal of Ethnopharmacology, 2009

Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmani... more Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmaniasis, using herbal drugs. The efficacy, dosage, safety and active principles of most of the herbal preparations are not known. Extracts from 6 selected plant species, used as medicinal plants by indigenous local communities in Kenya, were screened for in vitro anti-plasmodial and anti-leishmanial activity, against 2 laboratory-adapted Plasmodium falciparum isolates (D6, CQ-sensitive and W2, CQ-resistant) and Leishmania major (IDU/KE/83 = NLB-144 strain), respectively. The methanol extract of Suregada zanzibariensis leaves exhibited good anti-plasmodial activity (IC 50 4.66 ± 0.22 and 1.82 ± 0.07 g/ml for D6 and W2, respectively). Similarly, the methanol extracts of Albizia coriaria (IC 50 37.83 ± 2.11 g/ml for D6) and Aspergillus racemosus (32.63 ± 2.68 and 33.95 ± 2.05 g/ml for D6 and W2, respectively) had moderate anti-plasmodial activity. Acacia tortilis (IC 50 85.73 ± 3.36 g/ml for W2) and Albizia coriaria (IC 50 71.17 ± 3.58 g/ml for W2) methanol extracts and Aloe nyeriensis var kedongensis (IC 50 87.70 ± 2.98 and 67.84 ± 2.12 g/ml for D6 and W2, respectively) water extract exhibited mild anti-plasmodial activity. The rest of the extracts did not exhibit any anti-plasmodial activity. Although the leishmanicidal activity of extracts were lower than for pentosam (80%), reasonable activity was observed for Aloe nyeriensis methanol (68.4 ± 6.3%), Albizia coriara water (66.7 ± 5.0%), Maytenus putterlickoides methanol (60.0 ± 6.23%), Asparagus racemosus methanol and water (58.3 ± 8.22 and 56.8 ± 6.58%, respectively), Aloe nyeriensis water (53.3 ± 5.1%) and Acacia tortilis water (52.9 ± 6.55%) extracts at 1000 g/ml. Leishmania major infected macrophages treated with methanol extracts of Suregada zanzibariensis and Aloe nyeriensis var kedongensis and Pentostam ® had infection rates of 28 ± 2.11, 30 ± 1.22 and 40 ± 3.69%, respectively at 1000 g/ml, indicating better anti-leishmanial activity for the extracts. The methanol extract of Albizia coriara (44.0 ± 3.69%) and aqueous extracts of Asparagus racemosus (42 ± 3.84%) and Acacia tortilis (44 ± 5.59%) had similar activity to pentosam ® . Multiplication indices for Leishmania major amastigotes treated with methanol extracts of Albizia coriaria, Suregada zanzibariensis and Aloe nyeriensis var kedongensis, aqueous extract of Acacia tortilis and pentosam ® were 28.5 ± 1.43, 29.4 ± 2.15, 31.1 ± 2.22, 35.9 ± 3.49 and 44.0 ± 3.27%, respectively, at 1000 g/ml, confirming better anti-leishmanial activity for the extracts. Aqueous extracts of Aloe nyeriensis (46.7 ± 3.28%) and Albizia coriaria (47.5 ± 3.21%) had similar activity level to pentosam ® . The plant extracts have better inhibitory activity while pentosam ® has better leishmanicidal activity. All extracts exhibited very low cytotoxicity (CC 50 > 500 g/ml) against human embryonic lung fibroblast (HELF) cells. The investigations demonstrated the efficacy and safety of some extracts of plants that are used by rural indigenous communities for the treatment of parasitic diseases.

Research paper thumbnail of The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya

Journal of Ethnopharmacology, 2008

The use of herbal drugs as combinations has existed for centuries in several cultural systems. Ho... more The use of herbal drugs as combinations has existed for centuries in several cultural systems. However, the safety and efficacy of such combinations have not been validated. In this study, the toxicity, anti-plasmodial and antimalarial efficacy of several herbal drug combinations were investigated. Lannea schweinfurthii, Turraea robusta and Sclerocarya birrea, used by traditional health practitioners in Meru community, were tested for in vitro anti-plasmodial and in vivo anti-malarial activity singly against Plasmodium falciparum and Plasmodium berghei, respectively. Methanolic extract of Turraea robusta was the most active against Plasmodium falciparum D6 strain. Aqueous extracts of Lannea schweinfurthii had the highest anti-plamodial activity followed by Turraea robusta and Sclerocarya birrea. D6 was more sensitive to the plant extracts than W2 strain. Lannea schweinfurthii extracts had the highest anti-malarial activity in mice followed by Turraea robusta and Sclerocarya birrea with the methanol extracts being more active than aqueous ones. Combinations of aqueous extracts of the three plants and two others (Boscia salicifolia and Rhus natalensis) previously shown to exhibit anti-plasmodial and anti-malarial activity singly were tested in mice. Marked synergy and additive interactions were observed when combinations of the drugs were assayed in vitro. Different combinations of Turraea robusta and Lannea schweinfurthii exhibited good in vitro synergistic interactions. Combinations of Boscia salicifolia and Sclerocarya birrea; Rhus natalensis and Turraea robusta; Rhus natalensis and Boscia salicifolia; Turraea robusta and Sclerocarya birrea; and Lannea schweinfurthii and Boscia salicifolia exhibited high malaria parasite suppression (chemo-suppression >90%) in vivo when tested in mice. The findings are a preliminary demonstration of the usefulness of combining several plants in herbal drugs, as a normal practice of traditional health practitioners.

Research paper thumbnail of The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya

Journal of Ethnopharmacology, 2008

Research paper thumbnail of Antimalarial activity of some plants traditionally used in treatment of malaria in Kwale district of Kenya

Journal of Ethnopharmacology, 2007

their cytotoxic effects. The most active extracts (IC(50)<10 microg/ml) screened against chloroqu... more their cytotoxic effects. The most active extracts (IC(50)<10 microg/ml) screened against chloroquine (CQ) sensitive (D6) and resistant (W2) P. falciparum clones, were the water and methanol extracts of Maytenus undata (Thunb.) Blakelock (Celasteraceae), methanol extracts of Flueggea virosa (Willd.) Voigt (Euphorbiaceae), Maytenus putterlickioides (Loes.) Excell and Mendoca (Celastraceae), and Warburgia stuhlmannii Engl. (Canellaceae). These extracts showed various cytotoxic levels on Vero E6 cells with the water extract of M. undata exhibiting least cytotoxicity. At least one of the extracts of the plant species exhibited a high chemo suppression of parasitaemia >70% in a murine model of P. berghei infected mice. These results indicate that there is potential for isolation of a lead compound from the extracts of the five plants. W. stuhlmannii and M. putterlickioides have not been reported before for antiplasmodial activity.

Research paper thumbnail of Determining the Prevalence and Risk Factors Associated with Leishmaniasis among Residents of Rural Marigat Sub-County, Baringo County- Kenya

Current Overview on Disease and Health Research Vol. 1

Research paper thumbnail of Chemical Synthesis, Efficacy, and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds

Journal of Tropical Medicine

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...

Research paper thumbnail of Chemical Synthesis, Efficacy and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds

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...

Research paper thumbnail of Quality of Water and the Recovery Time of Malnourished Children Enrolled In a Nutritional Feeding Programme: Lessons from Parkishon Region, Marsabit County, Kenya

Archives of Clinical and Medical Case Reports

Objective: Malnutrition is a problem that continues to plague children from resource scarce regio... more Objective: Malnutrition is a problem that continues to plague children from resource scarce regions of Kenya. To address this health challenge, the government of Kenya initiated feeding programmes aimed at improving the daily nutritional food intake of underweight and sickly children from these regions. This study examined the relationship between the quality of water and the children's recovery as measured by the Mid-Upper Arm Circumference (MUAC) in Parkishon region of Kenya. Methods: The study followed 82 underweight children on a PlumpNut diet. Thirty seven (37) children were using water from a water backpack while the other children were using water from Silanga, a dam that is the only source of water in the region. The recovery time of the children was measured using the MUAC index. Results: Of the 37 children enrolled in the nutritional feeding programme and from families that received the water backpack, 10 recovered fully within three months and were put off the nutritional supplement program. The underweight children in the same nutritional feeding programme but whose families did not receive the water backpack, and therefore continued to consume water from the dam, are yet to recover and are still enrolled in the nutritional feeding programme.

Research paper thumbnail of Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model

Malaria journal, Jul 3, 2017

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...

Research paper thumbnail of In Situ Preparation of Chiral Bifunctional Catalysts and Their Application to Asymmetric Michael Addition Reactions

Asian Journal of Organic Chemistry, 2012

Research paper thumbnail of ChemInform Abstract: Diastereoselective Arylation of Enantiopure 3-Bromopiperidin-2-one Derived from (R)-(-)-2-Phenylglycinol with Organocuprate Reagents

ChemInform, 2012

Diastereoselective Arylation of Enantiopure 3-Bromopiperidin-2-one Derived from (R)-(-)-2-Phenylg... more Diastereoselective Arylation of Enantiopure 3-Bromopiperidin-2-one Derived from (R)-(-)-2-Phenylglycinol with Organocuprate Reagents.-The 3-bromolactam (I) derived from (R)-2-phenylglycinol undergoes a stereoselective reaction with arylcuprate reagents.-(ROMERO, O.;

Research paper thumbnail of Diastereoselective arylation of l-proline derivatives at the 5-position

Tetrahedron, 2008

Diastereoselective introduction of nucleophiles into L-proline derivatives at the 5-position was ... more Diastereoselective introduction of nucleophiles into L-proline derivatives at the 5-position was achieved with suitable selection of N-protecting group. N-Methoxycarbonylated or benzyloxycarbonylated L-proline derivatives reacted with arene to give cis-arylated products. On the other hand, N-benzoylated L-proline derivative preferentially gave trans-arylated product which could be easily transformed into optically active C 2-symmetrical pyrrolidine derivative. Such derivative 5, worked well as an organic activator in the asymmetric reduction of aromatic imines by Cl 3 SiH.

Research paper thumbnail of Antiplasmodial and cytotoxicity activities of some selected plants used by the Maasai community, Kenya

South African Journal of Botany, 2011

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

Research paper thumbnail of Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy

Current Medicinal Chemistry, 2011

Efforts to develop an effective malaria vaccine are yet to be successful and thus chemotherapy re... more Efforts to develop an effective malaria vaccine are yet to be successful and thus chemotherapy remains the mainstay of malaria control strategy. Plasmodium falciparum, the parasite that causes about 90% of all global malaria cases is increasingly becoming resistant to most antimalarial drugs in clinical use. This dire situation is aggravated by reports from Southeast Asia, of the parasite becoming resistant to the "magic bullet" artemisinins, the last line of defense in malaria chemotherapy. Drug development is a laborious and time consuming process, and thus antimalarial drug discovery approaches currently being deployed largely include optimization of therapy with available drugs-including combination therapy and developing analogues of the existing drugs. However, the latter strategy may be hampered by crossresistance, since agents that are closely related chemically may share similar mechanisms of action and/or targets. This may render new drugs ineffective even before they are brought to clinical use. Evaluation of drug-resistance reversers (chemosensitizers) against quinoline-based drugs such as chloroquine and mefloquine is another approach that is being explored. Recently, evaluation of new chemotherapeutic targets is gaining new impetus as knowledge of malaria parasite biology expands. Also, single but hybrid molecules with dual functionality and/or targets have been developed through rational drug design approach, termed as "covalent bitherapy". Since desperate times call for radical measures, this review aims to explore novel rational drug-design strategies potentially capable of revolutionizing malaria therapy. We thus explore malaria apoptosis machinery as a novel drug target, and also discuss the potential of hybrid molecules as well as prodrugs and double prodrugs in malaria chemotherapy.

Research paper thumbnail of Electrochemical Deallylation of α-Allyl Cyclic Amines and Synthesis of Optically Active Quaternary Cyclic Amino Acids

Chemistry - A European Journal, 2010

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.

Research paper thumbnail of Tigliane Diterpenoids from the Stem Bark of Neoboutonia macrocalyx

Neoboutonia macrocalyx is a plant used by traditional healers among the Meru community in Kenya. ... more Neoboutonia macrocalyx is a plant used by traditional healers among the Meru community in Kenya. Chromatographic fractionation of the petroleum ether and dichloromethane extracts of this plant yielded one known (1) and three new tigliane-type diterpenoids (2-4). The chemical structures of the isolated compounds were established through spectroscopic data interpretation.

Research paper thumbnail of Anti-plasmodial activity of the extracts of some Kenyan medicinal plants

Journal of Ethnopharmacology, 2009

Ethnopharmacological relevance: The spread of drug resistant Plasmodium falciparum strains necess... more Ethnopharmacological relevance: The spread of drug resistant Plasmodium falciparum strains necessitates search for alternative newer drugs for use against malaria. Medicinal plants used traditionally in preparation of herbal medicines for malaria are potential source of new anti-malarial drugs. Aim of the Study: To identify the anti-plasmodial potential of twelve plants used in preparing herbal remedies for malaria in Kilifi and Tharaka districts of Kenya. Materials and Methods: Twelve plants used traditionally for anti-malarial therapy in Kilifi and Tharaka districts were extracted with water/methanol yielding twenty-three extracts. The extracts were tested against chloroquine sensitive (NF54) and resistant (ENT30) P. falciparum strains in vitro using 3 Hypoxanthine assay. Results: Seven (30%) extracts showed activity against P. falciparum with IC 50 values below 20 g/ml. The remaining 16 extracts showed low or no activity. The most active extracts were from Zanthoxylum chalybeum (Rutaceae) with an IC 50 value of 3.65 g/ml, Cyperus articulatus (Cyperaceae) with 4.84 g/ml, and Cissampelos pareira (Menispermaceae) with 5.85 g/ml. Conclusions: This study revealed plants, that are potential sources of anti-malarial compounds. Antiplasmodial activities of extracts of T. simplicifolia, C. pareira, and C. articulatus are reported for the first time.

Research paper thumbnail of Antimalarial activity of some plants traditionally used in treatment of malaria in Kwale district of Kenya

Journal of Ethnopharmacology, 2007

Developing countries, where malaria is endemic, depend strongly on traditional medicine as a sour... more Developing countries, where malaria is endemic, depend strongly on traditional medicine as a source for inexpensive treatment of this disease. However, scientific data to validate the antimalarial properties of these herbal remedies are scarce. Consequently, it is important that antimalarial medicinal plants are investigated, in order to establish their efficacy and to determine their potential as sources of new antimalarial drugs. In this study, we evaluated the claimed antimalarial properties of fifty eight crude extracts from fifteen plants used in traditional medicine against malaria and fever, mainly from Southern African regions. The air-dried powdered plant parts (roots, leaves, seeds or bark) or whole plants were extracted, sequentially, with solvents of increased polarity (n-hexane, dichloromethane, ethyl acetate and methanol). Schizontocidal activity was measured using a standard in vitro assay, with 3D7 Plasmodium falciparum strain. From the 58 extracts tested, two of them showed a significant activity (IC 50 < 5 µg/mL), and 34.5 % showed a moderate activity (10 < IC 50 < 50 µg/mL). A bioassay-guided fractionation of the most active extracts is ongoing.

Research paper thumbnail of Anti-plasmodial activity and toxicity of extracts of plants used in traditional malaria therapy in Meru and Kilifi Districts of Kenya

Journal of Ethnopharmacology, 2006

The methanol and aqueous extracts of 10 plant species (Acacia nilotica, Azadirachta indica, Caris... more The methanol and aqueous extracts of 10 plant species (Acacia nilotica, Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii, Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro anti-plasmodial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of the methanol extracts were toxic to the brine shrimp (LD 50 < 100 g/ml), while 50% showed in vitro anti-plasmodial activity (IC 50 < 100 g/ml). The methanol extract of the stem bark of N. macrocalyx had the highest toxicity to brine shrimp nauplii (LD 50 21.04 ± 1.8 g/ml). Methanol extracts of the rest of the plants exhibited mild or no brine shrimp toxicity (LD 50 > 50 g/ml). The aqueous extracts of N. macrocalyx had mild brine shrimp toxicity (LD 50 41.69 ± 0.9 g/ml), while the rest were lower (LD 50 > 100 g/ml). The methanol extracts of F. angolensis and Zanthoxylum usambarense had IC 50 values <6 g/ml while the aqueous ones had values between 6 and 15 g/ml, against both chloroquine-sensitive and resistant P. falciparum strains. The results support the use of traditional herbs for anti-malarial therapy and demonstrate their potential as sources of drugs.

Research paper thumbnail of Anti-parasitic activity and cytotoxicity of selected medicinal plants from Kenya

Journal of Ethnopharmacology, 2009

Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmani... more Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmaniasis, using herbal drugs. The efficacy, dosage, safety and active principles of most of the herbal preparations are not known. Extracts from 6 selected plant species, used as medicinal plants by indigenous local communities in Kenya, were screened for in vitro anti-plasmodial and anti-leishmanial activity, against 2 laboratory-adapted Plasmodium falciparum isolates (D6, CQ-sensitive and W2, CQ-resistant) and Leishmania major (IDU/KE/83 = NLB-144 strain), respectively. The methanol extract of Suregada zanzibariensis leaves exhibited good anti-plasmodial activity (IC 50 4.66 ± 0.22 and 1.82 ± 0.07 g/ml for D6 and W2, respectively). Similarly, the methanol extracts of Albizia coriaria (IC 50 37.83 ± 2.11 g/ml for D6) and Aspergillus racemosus (32.63 ± 2.68 and 33.95 ± 2.05 g/ml for D6 and W2, respectively) had moderate anti-plasmodial activity. Acacia tortilis (IC 50 85.73 ± 3.36 g/ml for W2) and Albizia coriaria (IC 50 71.17 ± 3.58 g/ml for W2) methanol extracts and Aloe nyeriensis var kedongensis (IC 50 87.70 ± 2.98 and 67.84 ± 2.12 g/ml for D6 and W2, respectively) water extract exhibited mild anti-plasmodial activity. The rest of the extracts did not exhibit any anti-plasmodial activity. Although the leishmanicidal activity of extracts were lower than for pentosam (80%), reasonable activity was observed for Aloe nyeriensis methanol (68.4 ± 6.3%), Albizia coriara water (66.7 ± 5.0%), Maytenus putterlickoides methanol (60.0 ± 6.23%), Asparagus racemosus methanol and water (58.3 ± 8.22 and 56.8 ± 6.58%, respectively), Aloe nyeriensis water (53.3 ± 5.1%) and Acacia tortilis water (52.9 ± 6.55%) extracts at 1000 g/ml. Leishmania major infected macrophages treated with methanol extracts of Suregada zanzibariensis and Aloe nyeriensis var kedongensis and Pentostam ® had infection rates of 28 ± 2.11, 30 ± 1.22 and 40 ± 3.69%, respectively at 1000 g/ml, indicating better anti-leishmanial activity for the extracts. The methanol extract of Albizia coriara (44.0 ± 3.69%) and aqueous extracts of Asparagus racemosus (42 ± 3.84%) and Acacia tortilis (44 ± 5.59%) had similar activity to pentosam ® . Multiplication indices for Leishmania major amastigotes treated with methanol extracts of Albizia coriaria, Suregada zanzibariensis and Aloe nyeriensis var kedongensis, aqueous extract of Acacia tortilis and pentosam ® were 28.5 ± 1.43, 29.4 ± 2.15, 31.1 ± 2.22, 35.9 ± 3.49 and 44.0 ± 3.27%, respectively, at 1000 g/ml, confirming better anti-leishmanial activity for the extracts. Aqueous extracts of Aloe nyeriensis (46.7 ± 3.28%) and Albizia coriaria (47.5 ± 3.21%) had similar activity level to pentosam ® . The plant extracts have better inhibitory activity while pentosam ® has better leishmanicidal activity. All extracts exhibited very low cytotoxicity (CC 50 > 500 g/ml) against human embryonic lung fibroblast (HELF) cells. The investigations demonstrated the efficacy and safety of some extracts of plants that are used by rural indigenous communities for the treatment of parasitic diseases.

Research paper thumbnail of The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya

Journal of Ethnopharmacology, 2008

The use of herbal drugs as combinations has existed for centuries in several cultural systems. Ho... more The use of herbal drugs as combinations has existed for centuries in several cultural systems. However, the safety and efficacy of such combinations have not been validated. In this study, the toxicity, anti-plasmodial and antimalarial efficacy of several herbal drug combinations were investigated. Lannea schweinfurthii, Turraea robusta and Sclerocarya birrea, used by traditional health practitioners in Meru community, were tested for in vitro anti-plasmodial and in vivo anti-malarial activity singly against Plasmodium falciparum and Plasmodium berghei, respectively. Methanolic extract of Turraea robusta was the most active against Plasmodium falciparum D6 strain. Aqueous extracts of Lannea schweinfurthii had the highest anti-plamodial activity followed by Turraea robusta and Sclerocarya birrea. D6 was more sensitive to the plant extracts than W2 strain. Lannea schweinfurthii extracts had the highest anti-malarial activity in mice followed by Turraea robusta and Sclerocarya birrea with the methanol extracts being more active than aqueous ones. Combinations of aqueous extracts of the three plants and two others (Boscia salicifolia and Rhus natalensis) previously shown to exhibit anti-plasmodial and anti-malarial activity singly were tested in mice. Marked synergy and additive interactions were observed when combinations of the drugs were assayed in vitro. Different combinations of Turraea robusta and Lannea schweinfurthii exhibited good in vitro synergistic interactions. Combinations of Boscia salicifolia and Sclerocarya birrea; Rhus natalensis and Turraea robusta; Rhus natalensis and Boscia salicifolia; Turraea robusta and Sclerocarya birrea; and Lannea schweinfurthii and Boscia salicifolia exhibited high malaria parasite suppression (chemo-suppression >90%) in vivo when tested in mice. The findings are a preliminary demonstration of the usefulness of combining several plants in herbal drugs, as a normal practice of traditional health practitioners.