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University of Nairobi (2018)

Phytochemical investigation of selected tephrosia species for antiplasmodial and anti-inflammatory principles

Assefa, Yoseph A

Titre : Phytochemical investigation of selected tephrosia species for antiplasmodial and anti-inflammatory principles

Auteur : Assefa, Yoseph A

Université de soutenance : University of Nairobi

Grade : Doctor of Philosophy (PhD) in chemistry 2018

Résumé
Malaria is one of the major diseases affecting human beings, whose symptoms include pain and inflammation. It is caused by five Plasmodium species of which P. falciparum and P. vivax are the important causative agents of human malaria. From the time P. falciparum showed evidence of resistance towards the most recently introduced antimalarial drugs ; the degree of malaria infection has increased. Malaria causes inflammation and pain ; some of the drugs used to treat these conditions have side effects while others are not affordable to the majority the third world countries. Therefore, there is an urgent need for new antimalarial and anti-inflammatory agents that lack side-effects and resistance associated with the currently used drugs. In this study, six Tephrosia species ; T. aequilata, T. elata, T. noctiflora, T. pumila, T. purpurea subsp. leptostachya and T. rhodesica were investigated with the aim of identifying their antiplasmodial and anti-inflamatory principles. The stem bark, roots and leaves of these plants were collected, dried, ground and extracted with dichloromethane/methanol (1:1) by cold percolation at room temperature. The crude extracts of these plants were subjected to column chromatography on silica gel. Based on the TLC profile of the fractions, further purification was done using Sephadex LH-20, preparative HPLC, preparative TLC, and crystallization techniques. As a result, from the six Tephrosia species, fifty compounds were isolated and three derivatives prepared. Thirteen of the isolated compounds are new. From the roots of T. aequilata, four new compounds [aequichalcone A (168), aequichalcone B (169), aequichalcone C (170) and 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (167)] and seven known compounds were isolated. From the seedpods and leaves of T. elata, a total of nineteen compounds were isolated and characterized. The roots of T. rhodesica gave twenty one compounds, of which five are new compounds [rhodimmer (183), rhocarpin (188), rhodiflavan A (191), rhodiflavan B (192), rhodiflavan C (193)). From stem of T. purpurea spp. leptostachya, four new compounds [(E)-5-hydroxy-tephrostachin (198), purleptone (194), (E)-5-oxo- anhydrotephrostachin (195) and terpurlepflavone (199)] and seven previously reported compounds were isolated. From the stem of T. noctiflora, three compounds, two of which are flavonoids were isolated and characterized. Three compounds were isolated and characterized from the aerial part of T. pumila. Characterization of the iolated compounds was done using a combination of spectroscopic techniques including, UV, 1D-NMR (1H-NMR, 13C-NMR, DEPT), 2D (HMBC, HSQC, COSY) and MS. The crude extracts and the isolated compounds were evaluated for antiplasmodial activities against the chloroquine-sensitive 3D7 and D6 strains of P. falciparum. Among the pure compounds (E)-5-hydroxy-tephrostachin (198) (IC50 1.7+0.1 M) was the most active against the chloroquine-sensitive (D6) strain with a much lower cytotoxicity, (IC50 > 21 M) against four cell-lines. Aequichalcone C (168), (IC50 2.48 ± 0.22 μM), obovatachalcone (147) (IC50 4.23 ± 1.11 μM) and praecansone B (146) (4.14 ± 0.26 μM) showed good activity against the 3D7 strain. Rhodiflavan A (191) showed good (3.6 ± 1.0 μM) and moderate (6.5 ± 0.9 μM) activity against the 3D7 and D6 strains, respectively. Anti-inflammatory and anti-nociceptive activities for some of the extracts and pure compounds were also evaluated using the formalin test. Tachrosin (41) reduced pain by 50.4% (in the early phase) and 49.2% (in the late phase). Kaempferitrin (200) reduced pain by 49% (in the early phase) and 44% (in the later phase). The reference drug diclofenac, reduced pain by 53.4% (in the early phase) and 62% (in the late phase). Overall, from this study 50 compounds including 13 new flavonoids were isolated from the selected Tephrosia species and some of these new flavonoids showed significant antiplasmodial and anti-inflammatory activities. Further studies should be directed at testing the flavonoids of Tephrosia species for in vivo antiplsmodial activity and toxicity.

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