Phytochemical Investigation of Selected Plants in the Families Anacardiaceae and Easterner for Bioactive Principles

Abstract

This thesis describes an investigation of two plants from Anacardiaceae plant family namely Lannea rivae (Chiov) Sacleux and Lannea schweinfurthii (Engl.) Engl. and three other plants from Asteraceae family; Psiadia punctulata Vatke, Aspilia pluriseta Schweinf. and Aspilia mossambicensis (Oliv.) Wild for their bioactive principles. Chromatographic separation of different extracts from the five plants led to the identification of a total of seventy six compounds among which ten were new, and fourteen derivatives obtained by chemical derivatization. Three structures wrongly reported in the literature were corrected. The structure elucidation of the compounds was performed by using Nuclear Magnetic Resonance (NMR), Ultra Violet (UV), Infra-Red (IR), Optical Rotation (OR) and Mass Spectrometric (MS) techniques. In the case of seventen compounds X-ray crystallography was used. The isolated compounds and crude extracts were tested for their cytotoxicity, antimicrobial, antiinflammatory, antiplasmodial and antidiabetic activities. The root extract of Lannea rivae resulted in isolation of seven compounds of which the alkenylcyclohexanone derivatives; (4R,6S)-4,6-dihydroxy-6-((Z)-nonadec-14′-en-1-yl)cyclohex-2-en-1-one (186) and (2S*,4R*,5S*)-2,4,5-trihydroxy-2-((Z)-nonadec-14′-en-1-yl)cyclohexanone (187) are new. The known compounds include taraxerol (188), taraxerone (189), β-sitosterol (190), epicatechin gallate (191), and 3’’,5’’-dimeyhoxy-epicatechin gallate (192). Epicatechin gallate showed high antimicrobial activity against Staphylococcus aureus and Escherichia coli, but most of the known compounds isolated from this plant were not effective against the two strains. From the stem bark of L. rivae, two known compounds were isolated, namely lupeol (193) and daucosterol (194). Roots extracts of Lannea schweinfurthii resulted in the identification of seven compounds namely 3-((E)-nonadec-16'-enyl)phenol (195), 1-((E)- heptadec-14'-enyl)cyclohex-4-ene-1,3-diol (196), 1-((E)-tridecadec-10'-enyl)cyclohex-4-en- 1,3-diol (197), 1-((E)-pentadec-12'-enyl)cyclohex-4-ene-1,3-diol (198), 1-((E,E)-nonadeca- 12',14'-dienyl)cyclohex-4-en-1,3-diol (199), 1-((E)-nonadec-16'-enyl)cyclohex-4-en-1,3-diol (200) and catechin (201). The stem bark of L. schweinfurthii resulted in the isolation of seven compounds; 4,4'-diydroxy-3-methoxy-3'-O-glucosyl-ellagic acid (202), 4,4'-dihydroxy-3- methoxy-3'-O-[rhamnopyranosyl-(1 →2)] rhamnopyranoside ellagic acid (203), 3- ((12'Z,14'E)-heptadeca-dienyl)phenol (204), 188, 189, 195 and 198. xxii Phytochemical study of the leaves of Psiadia punctulata led to the identification of twenty one compounds of which eight are new diterpene: trachyloban-17-oic acid (205), ent-17- hydroxy-trachyloban-20-oic acid (206), ent-[6β,18,19]-trihydroxy-trachyloban-2-one (207), normal-trachyloban-2α,18,19-triol (208), normal trachyloban-2α,6α,19-triol (209), ent- 15β,16α,17-trihydroxy-kauran-19-oic acid methyl ester (214) and compounds 219b-c. From the stem bark of P. punctulata, six compounds were identified. These include 7α-hydroxyent- trachyloban-19-oic acid (225), friedelan-3β-ol (226), spinasterol (227), (S)-2,3- dihydroxypropyl tridecanoate (228) and 5-hydroxy-7,2',3',4',5'-pentamethoxy-flavone (220) and 5,7-dihydroxy-2',3',4',5'-tetra-methoxy-flavone (221). Analysis of the roots of P. punctulata led to the identification of six compounds; ent-trachylobane-2α,6β,18,19-tetraol (229), ent-kauren-16-en-2-one (230), friedelin (231), 24,25-dihydro-lanost-8(9)-en-3β-ol (232), (6R, 7R)-bisabolone (233) and 221. Compounds 207 (CC50=6.41±0.2 μM) and 210 (CC50=3.4 ± 0.1 μM) are the most cytotoxic against Hep-G2 and DU-145 cell lines respectively. From the roots of Aspilia pluriseta, nine kaurene derivatives; 12α-methoxy-entkaura- 9(11),16-dien-19-oic acid (234) and 16α-hydroxy-ent-kauran-19-oic acid (235), 9β- hydroxy-15α-angeloyloxy-ent-kaur-16-en-19-oic acid (236), 15α-angeloyloxy-ent-kaur- 16α,17-epoxy-ent-kauran-19-oic acid (237), methyl-9β-hydroxy-15α-angeloyloxy-ent-kaur- 16-en-19-oate (238), 15α-angeloyloxy-ent-kaur-16-en-19-oic acid (239), ent-kaura-9(11),16- dien-19-oic (240), ent-kaura-9(11),16-dien-12-one (241), methyl-ent-kaur-16-en-19-oate (242) were isolated. The seven other compounds isolated from the roots are kaurene also diterpenes derivatives (236-242). The aerial part of A. pluriseta let to the identification of seven compounds; ent-kaur-16-en-19-oic acid (243), ent-kaur-16-en-19-ol (244), ent-kaur- 16-ene (245), lanosterol (246), stigmasta-5,22(E)-dien-3β-ol (247), 3β-hydroxy-olean-12-en- 29-oic acid (248), carissone (249). Oral glucose tolerance test results revealed that the crude extract of A. pluriseta reduced the blood glucose level more than any other isolated compounds. Seven compounds namely methyl-15α-angeloyloxy-ent-kaur-16-en-19-oate (250), 12-oxo-ent-kaura-9(11),16-dien-19-oic acid (251), ent-kauran-19-oic acid (252), 3β- hydroxyolean-12-en-28-oic acid (253), 236, 237, 238 were also isolated and identified from the root of Aspilia mossambicensis (Asteraceae). The aerial part of the same plant, A. mossambicensis resulted in the identification of β-amyrin acetate (254), kaura-9(11),16-diene (255), 15β-hydroxy-kaura-9(11),16-diene (256), methyl cinnamate (257), 240, 243 and 247. xxiii Ten derivatives (258-267) were prepared from the isolated compounds of Psiadia punctulata. Four more compounds (268-271) were derivatized from the isolated compounds of Aspilia pluriseta. Among these derivatives, compound 265 was found to be active (CC50 = 16.9 ± 5.1 μM) against the growth of A549 cancer cell line. Compound 270 was the most antimicrobial against Staphylococcus aureus, Escherichia. coli and Candida parapsilosis having an inhibition zone of 8 mm against each strains. O HO HO OH H H O OH H H H O OCH3 OH OH OH H 205 214 207 HO O OH 206 HO HO OH HO H H HO OH 208 209 O OH OH O OH OH HO 186 187 OH O H H3CO H 235 234 OH O O O H H O 237 N NH OCH3 OCH3 OCH3 H3CO OH OH H3CO 260 O O H3CO OCH3 OCH3 OCH3 OH RO Br Br R = OCH3 261 R = H 262 OH O H OH H 1