Secondary metabolites of the leaves of Tricalysia atherura N. Hallé (Rubiaceae) and their potential antiplasmodial activity.

One monoterpene indole alkaloid, atheruramine (1) bearing an ether bridge linking, one hydrobenzoin derivative, tricalydioloside (2) and two ursane-type triterpenes, atherurosides (A and B) (3 and 4) were isolated from the leaves of Tricalysia atherura, together with eight known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the relative configurations of compounds 1-3 were established by NOE difference. Four of the metabolites were screened in vitro against both chloroquine (CQ)-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum; they were found to exhibit moderate activity against chloroquine-resistant (Dd2) (IC50 64.99-92.29 µg/mL). Meanwhile, crude extract possesses high antiplasmodial activity against both 3D7 and Dd2 strains of P. falciparum (IC50 4.39-7.54 µg/mL) and high selectivity indices values (SI > 10) and was found to be safe.

Decoding the reaction mechanism of the cyclocondensation of ethyl acetate2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl) polyazaheterocycle and ethylenediamine using bond evolution theory.

We investigated the flow of electron density along the cyclocondensation reaction between ethyl acetate 2-oxo-2-(4-oxo-4H-pyrido[1.2-a]pyrimidin-3-yl) polyazaheterocycle (1) and ethylenediamine (2) at the ωB97XD/6-311++G(d,p)computational method within of bond evolution theory (BET). The exploration of potential energy surface shows that this reaction has three channels (1-3) with the formation of product 3 via channel-2 (the most favorable one) as the main product and this is in good agreement with experimental observations. The BET analysis allows identifying unambiguously the main chemical events happening along channel-2. The mechanism along first step (TS2-a) is described by a series of four structural stability domains (SSDs), while five SSDs for the last two steps (TS2-b and TS2-c). The first and third steps can be summarized as follows, the formation of N1-C6 bond (SSD-II), then, the restoration of the nitrogen N1 lone pair (SSD-III), and finally, the formation of the last O1-H1 bond (SSD-IV). For the second step, the formation of hydroxide ion is noted, as a result of the disappearance of V(C6,O7) basin and the transformation of C6-N1 single bond into double one (SSD-IV). Finally, the appearance of V(O7,H2) basin lead to the elimination of water molecule within the last domain is observed.

Antimicrobial and cytotoxic activities of indole alkaloids and other constituents from the stem barks of Rauvolfia caffra Sond (Apocynaceae).

Twenty indole alkaloids, among which two undescribed ones named rauvolfianoids A (1) and B (2), were isolated from the stem barks of Rauvolfia caffra Sond along with eight other compounds from other biosynthetic pathways. The structures were elucidated by analysis of spectroscopic data, including 1 D and 2 D NMR; absolute configurations of 1 and 2 were determined by CD exciton chirality method. Compounds 1 and 2 were evaluated for antimicrobial and anticancer activities against three bacterial strains (Escherichia coli, Shigella sp and Salmonella sp) and CRC-related opportunistic pathogens. 1 showed moderate antibacterial activity against Salmonella sp with the MIC value of 25 µg/ml, while 2 exhibited weak selective activity against all tested pathogens. In addition, these alkaloids were characterized as weak apoptosis inducers in HCT116 human colon carcinoma cell line.

Antibacterial and cytotoxic activities of undescribed cassiaric acid and other constituents from Cassia arereh stem barks.

A new lupane-type triterpene, 2α,3ß-dihydroxylupan-29-oic acid (1), and one new ceramide derivative: (2S*,2'R*,3S*,4R*,5R*,7'E,11E,12'E,20E)-N-[2'-hydroxyoctadeca-6,11-dienoyl]-2-aminohexacosa-11,20-diene-1,3,4,5-tetrol (2) were isolated from the ethyl acetate fraction obtained from the methanol extract of the stem barks of Cassia arereh together with seven known compounds. Their structures were characterized using two-dimensional NMR, mass spectrometry, and compared with reported data. To date, this is the first report of the isolation of a multiple double bonds sphingolipid type (2) from this genus. The ethyl acetate extract and selected isolates were examined for antimicrobial and cytotoxic activities in vitro. Betulinaldehyde (5) has shown to be active against all bacterial strains whereas, cassiaric acid (1) and betulinic acid (6) have demonstrated to be moderately active. In addition, cassiaric acid (1) showed the best cytotoxic result against HeLa and MCF-7 cell lines tested with IC50 75.00 µM, while lupeol (3) and betulinic acid (6) displayed weak cytotoxicity at 100.00 µM.

Antiplasmodial activities of indole alkaloids from Tabernaemontana penduliflora K. Schum (Apocynaceae).

Five undescribed carboxy-indole alkaloids with corynanthe skeleton, penduflorines A-E (1-3) as well as a voacangine-N-oxide alkaloid, tabernaemontine (4), were isolated along with eight other known compounds (5-12) from the trunk bark of Tabernaemontana penduliflora K. Schum (Apocynaceae). Their structures were determined by means of spectroscopic and spectrometric methods such as UV, IR, NMR and HR-ESI-MS. Antiplasmodial activities of new isolates were evaluated against two strains of Plasmodium falciparum 3D7 and Dd2 by the Sybr green I-based fluorescence assay setup. Those compounds showed good in vitro activities. Among them, penduflorines A and B (1a and 1b) as well as tabernaemontine (4) showed significant inhibitory activities against the two strains with IC50 values ranged between 1.85 and 7.88 µg/mL. This is the first report of quaternary-N-indole alkaloids (1a, 1b, 2, 3a, 3b and 4) occurring in the form of zwitterion from Tabernaemontana genus.

Antiplasmodial and antileishmanial inhibitory activity of triterpenes and steroidal alkaloid from the leaves of Funtumia elastica (Preuss) Stapf (Apocynaceae).

The phytochemical study of leaves of Funtumia elastica led to the isolation of three undescribed ursane derivatives, funtumic acids A, B and C (1-3), as well as one steroidal alkaloid, elasticine (4) and five other known compounds (5-9). Their structures were elucidated on the basis of NMR, MS, IR, UV spectroscopic data as well as by comparison with the literature. The compound 5-hydroxypyridine-3-carboxamide (9) was isolated for the first time from the Apocynaceae family. All the isolated compounds were evaluated for their antiparasitic effects against 3D7 and Dd2 strains of Plasmodium falciparum and promastigotes of Leishmania donovani (MHOM/SD/62/1S). Compounds 1-4 possessed good in vitro antimalarial activities against CQR Dd2 with IC50 values ranging from 4.68 to 5.36 µg/mL and moderate on CQS 3D7. Only compounds 1 and 2 showed leishmanicidal activities with IC50 values ranging between 10.49 and 13.21 µg/mL. In addition, crude extract exhibited potent antiplasmodial (IC50 0.91 and 3.12 µg/mL) and antileishmanial (IC50 3.32 µg/mL) activities, thus demonstrating their potential synergistic action.

Antileishmanial activity of long chain alkyl benzene and other constituents from seeds of Sesamum indicum. L (Pedaliaceae).

The methanolic extract of the waste seeds of Sesamum indicum L. (Pedaliaceae) was subjected to chromatographic fractionation; it led to the isolation of an alkyl benzene identified as 1,3-bis (pentadecyl)benzene (1) along with three known fatty acids: oleic acid (2), linoleic acid (3), and palmitic acid (4); one monosaturated cardanol, 3-pentadecylphenol (5) and two phytosteroids identified as sitostanol (6) and campestanol (7). The structures of these compounds were elucidated by chemical and spectroscopic analyses. Compounds 1, 5 and 6 were evaluated against protozoan parasites. Compound 1 moderately inhibited the promastigote form of Leishmania donovani LG13 with IC50 equal to 16.9 µM.

In vitro antitubercular activity of extract and constituents from the stem bark of Disthemonanthus benthamianus

ABSTRACT A new C-glycosylflavone, apigenin 7-methyl ether 6-C-[β-xylopyranosyl-(1→3)-β-glucopyranoside] named distemonanthoside was isolated from the stem bark of Distemonanthus benthamianus Baill., Fabaceae, along with six known compounds, sitosterol 3-O-β-D-glucopyranoside, 4-methoxygallic acid, syringic acid, quercetin, 6"-O-acetylvitexin, quercetin 3-O-β-D-glucopyranoside. The structures of those compounds and others were determined through spectral analyses. Compounds distemonanthoside, sitosterol 3-O-β-D-glucopyranoside, 4-methoxygallic acid and quercetin were tested against a clinical isolate strain of Mycobacterium tuberculosis AC 45; they exhibited good to moderate antitubercular activities with MIC values ranged from 31.25 to 125 µg/ml.