Arnold D Forkuo1, Charles Ansah2, Kwesi M Boadu3, Johnson N Boampong4, Elvis O Ameyaw5, Ben A Gyan6, Andrea T Arku7, Michael F Ofori8. 1. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. forkuoarnold@yahoo.com. 2. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. cansah.pharm@knust.edu.gh. 3. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. qwesimensah@gmail.com. 4. Department of Biomedical and Forensic Sciences, School of Biological Science, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana. jonboamus@yahoo.com. 5. Department of Biomedical and Forensic Sciences, School of Biological Science, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana. elvisameyaw@gmail.com. 6. Department of Immunology, Noguchi Memorial Institute for Biomedical Research, University of Ghana, Legon, Ghana. bgyan@noguchi.ug.edu.gh. 7. Department of Immunology, Noguchi Memorial Institute for Biomedical Research, University of Ghana, Legon, Ghana. atwumwaaarku@noguchi.ug.edu.gh. 8. Department of Immunology, Noguchi Memorial Institute for Biomedical Research, University of Ghana, Legon, Ghana. mofori@noguchi.ug.edu.gh.
Abstract
BACKGROUND: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. METHODS: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. RESULTS: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg(-1) po) and in combination with ART (4 mg kg(-1)) showed no significant difference compared to the control group. CONCLUSION: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.
BACKGROUND:Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. METHODS: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. RESULTS:CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg(-1) po) and in combination with ART (4 mg kg(-1)) showed no significant difference compared to the control group. CONCLUSION: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.
Authors: C W Wright; J Addae-Kyereme; A G Breen; J E Brown; M F Cox; S L Croft; Y Gökçek; H Kendrick; R M Phillips; P L Pollet Journal: J Med Chem Date: 2001-09-13 Impact factor: 7.446
Authors: Arnold D Forkuo; Charles Ansah; Kwesi M Boadu; Johnson N Boampong; Elvis O Ameyaw; Ben A Gyan; Andrea T Arku; Michael F Ofori Journal: Malar J Date: 2016-03-16 Impact factor: 2.979
Authors: Joy E Chiu; Isaline Renard; Anasuya C Pal; Pallavi Singh; Pratap Vydyam; Jose Thekkiniath; Madelyn Kumar; Shalev Gihaz; Sovitj Pou; Rolf W Winter; Rozalia Dodean; Lisa Frueh; Aaron C Nilsen; Michael K Riscoe; J Stone Doggett; Choukri Ben Mamoun Journal: Antimicrob Agents Chemother Date: 2021-08-17 Impact factor: 5.191
Authors: Elvis O Ameyaw; Kodwo B Asmah; Robert P Biney; Isaac T Henneh; Phyllis Owusu-Agyei; James Prah; Arnold D Forkuo Journal: Malar J Date: 2018-04-04 Impact factor: 2.979