Structure activity relationship studies on antileishmanial steroidal alkaloids from Sarcococca hookeriana

The search for antileishmanial constituents from the medicinal plant Sarcococca hookeriana (Buxaceae) of Nepalese origin has resulted in the isolation of 17 (1-17) active steroidal alkaloids. Compounds 1, 2, and 10 were subjected to derivatization and five chemically derived derivatives (1a, 2a, 10a, 10b, 10c) were also obtained. All these natural compounds and derivatives were found to have potent to mild antileishmanial properties. The IC(50) values were found to be in the range of 0.20-61.44 microg mL(-1) (IC(50) value of standard drug amphotericin B = 0.12 microg mL(-1)). The structure activity relationship indicated that the varieties of functionalities present in ring A of the steroidal alkaloids were found to play a characteristic role to increase the antileishmanial activity.     

Dimeric quinoline alkaloids

The review is denoted to an analysis of the literature on the investigation of dimeric quinoline alkaloids, which are divided into four groups depending on the structures of the terpenoid moiety. The natural sources, structures, stereochemical features, possible biogenetic schemes of formation, and methods of synthesizing the alkaloids of this group are considered.Institute of the Chemistry of Plant Substances, USSR Academy of Sciences, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 4–18, January–February, 1989.     

Synthesis, structure and stereochemistry of quinoline alkaloids from Choisya ternata

A range of seventeen quinoline alkaloids, involving several types of oxidations during their biosynthetic pathways, have been isolated from leaves of Choisya ternata. In addition to the nine known quinoline alkaloids, eight new members of the furoquinoline family, derived mainly from prenylation at C-5 (including two novel hydroperoxides), have been identified. The absolute configurations and enantiopurity values of all chiral quinoline alkaloids have been determined. One of the isolated alkaloids, 7-isopentenyloxy-gamma-fagarine, has been used as a precursor for the chemical asymmetric synthesis of the enantiopure alkaloids: evoxine, anhydroevoxine and evodine. The possible roles of oxygenase and other oxygen-atom-transfer enzymes, in the biosynthetic pathways of the C. ternata alkaloids, have been discussed.     

Megistoquinones I and II, two quinoline alkaloids with antibacterial activity from the bark of Sarcomelicope megistophylla

Two alkaloids, megistoquinone I (1) and megistoquinone II (2), were isolated from the bark of Sarcomelicope megistophylla. Their structures have been elucidated on the basis of MS and NMR data. Both belong to quinoline alkaloid series and should be considered as oxidation products of a furo[2,3-b]quinoline precursor. The two alkaloids showed antibacterial properties with minimum inhibitory concentration (MIC) ranging from 2.35 to 5.25 mg/ml for 1 and 0.73 to 1.23 mg/ml for 2.     

A novel flavonoid and furoquinoline alkaloids from Vepris glomerata and their antioxidant activity

The dichloromethane extract of the aerial part of the plant Vepris glomerata (Rutaceae) yielded a new flavonoid, which was accorded the trivial name veprisinol (1), together with four known furoquinoline alkaloids: haplopine-3,3'-dimethylallyl ether (2), anhydroevoxine (3), evoxine (4) and skimmianine (5). The structures of the compounds were established by 1D and 2D NMR spectroscopy, as well as HREIMS. Compounds 1 and 2 have strong antioxidant potential, similar to and in some instances better than ascorbic acid and can be used as beneficial additives to antioxidant supplements.     

Analysis of Amaryllidaceae alkaloids from Chlidanthus fragrans by GC-MS and their cholinesterase activity

The underivatized alkaloid mixture extracted from the bulbs of Chlidanthus fragrans Herb. was investigated by capillary GC/MS for the first time. Fifteen known Amaryllidaceae alkaloids of five structure types were identified. The main alkaloids were tazzetine (9, tazettine-type), chlidanthine (2, galanthamine-type), belladine (8, belladine-type) and lycorine (12, lycorine-type). The alkaloid extract from the bulbs showed promising human blood acetylcholinesterase (IC50 = 20.1 +/- 2.9 microg/mL) and human plasma butyrylcholinesterase (IC50 = 136.8 +/- 6.9 microg/mL) inhibitory activity.     

Diterpenoid alkaloids from the Chinese traditional herbal "Fuzi" and their cytotoxic activity

Ten diterpenoid alkaloids, including eight aconitine-type C??-diterpenoid alkaloids and two hetisine-type C??-diterpenoid alkaloids, were isolated from the secondary roots of Aconitum carmichaeli Debx., known as "Fuzi" in Chinese traditional herbal medicine. Their structures were established on the basis of their spectroscopic data and comparison with those of the literature. Among these alkaloids, chasmanine, oxonitine and 15-acetylsongoramine were isolated for the first time from this medicinal plant. The cytotoxic activity of the alkaloids were tested against several cell lines by the MTT method in which aconitine, hypaconitine, mesaconitne and oxonitine were found to strongly inhibit the growth of the HePG2 cell line, which showed that the existence and quantity of the ester groups have a significant influence on the cytotoxicity of the diterpenoid alkaloids.     

Structure elucidation and NMR assignments of two new pyrrolidinyl quinoline alkaloids from chestnut honey

The complete ¹H, ¹³C and ¹⁵N NMR spectral assignments of two new alkaloids isolated from chestnut honey and structurally related to kynurenic acid have been made using 1‐D and 2‐D NMR techniques, including COSY, HMQC and HMBC experiments. The new compounds have been identified as 3‐(2′‐pyrrolidinyl)‐kynurenic acid and its γ‐lactam derivative. Copyright © 2009 John Wiley & Sons, Ltd.     

Croomine- and tuberostemonine-type alkaloids from roots of Stemona tuberosa and their antitussive activity

Three new croomine-type Stemona alkaloids, tuberocrooline (1), 10-hydroxycroomine (2), and dehydrocroomine (3), and four new tuberostemonine-type alkaloids, tuberostemoline (4), tridehydrotuberostemonine (5), 9α-bisdehydrotuberostemonine (6), and 9α-bisdehydrotuberostemonine A (7), along with ten known constituents, were isolated from the roots of Stemona tuberosa collected from Yunnan province. The structures of the new compounds were established on the basis of one- and two-dimensional NMR spectra and other spectroscopic studies. The antitussive activity of the major alkaloids was tested using the citric acid-induced guinea pig cough model. Croomine (8) exhibited a dose-dependent inhibition of coughing with an ID₅₀ value of 0.18 mmol/kg.     

Haplodimerine — A new type of dimeric quinoline alkaloids

A base, which has been called haplodimerine, has been isolated from the fruit of the plantHaplophyllum foliosum Vved. It has been established by x-ray structural analysis that haplodimerine includes fragments of the known alkaloids skimmianine and flindersine attached to one another through the double bonds of furan and dimethylpyran rings with the formation of a four-membered ring.     

Electron impact mass spectrometry of hemiterpenoid tricyclic quinoline alkaloids

The mass spectral behaviour of some quinoline-type alkaloids, 3,4-dihydro-2H,5H-pyrano[3,2-c]quinolin-5-ones, isomeric 3,4-dihydro-2H,5H-pyrano[2,3-b]quinolin-5-ones and 2H,5H-pyrano[3,2-c]quinolin-5-ones, was studied in detail with the aid of linked scans, exact mass measurements and collisional spectrometry. The occurrence of a partial isomerization of the differently annulated isomers to a common, open-chain structure is discussed.     

Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-yl)methylene)-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl)(aryl)amides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442), Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), Aspergillus clavatus (MTCC 1323). All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.     

Antiparasitic activity of certain isoquinoline alkaloids and their hypothetical complexes with oligonucleotides

The antiparasitic activity of two tetrahydrodiisoquinoline alkaloids 2, 3, β-allocryptopine (4), protopine (5), and a substituted phenylethylamine 6 was studied. Compounds 2 and 6 inhibited the growth of the parasite Leishmania donovani. The capability of the examined compounds to bind DNA was estimated by molecular modeling. It has been shown that binding occurs in the small groove and primarily at the AT-enriched part of the oligonucleotide. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 270–274, May–June, 2008.     

Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2–11 were prepared by classical procedures. Including, five new esters derivatives 7–11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1–11 were confirmed by ¹H NMR, ¹³C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC₅₀ = 12.48 μg/mL) and the lowest cytotoxic derivative (CC₅₀ = 161.50 μg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.     

Daphniphyllum alkaloids with cytotoxic activity from Daphniphyllum angustifolium

A new Daphniphyllum alkaloid, daphnezomine W (1), together with four known ones, were isolated from the stems of Daphniphyllum angustifolium Hutch. Their structures were elucidated by spectroscopic methods and comparing with the literature data. Compound 1 was a new daphnezomine L-type alkaloid and exhibited moderate cytotoxic activity against Hela cell line with IC₅₀ of 16.0 μg/mL. A plausible biosynthetic pathway of 1 was also proposed.     

Isolation and cholinesterase activity of Amaryllidaceae alkaloids from Nerine bowdenii

Amaryllidaceae species are known as ornamental plants. Some contain galanthamine, an acetylcholinesterase inhibitor. The chemical composition of the alkaloid extract of bulbs of Nerine bowdenii Watson has been analyzed by means of GC/MS. Twenty-two compounds were detected and nineteen of them identified, one of which was belladine. The alkaloid extract showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 = 87.9 +/- 3.5 microg/mL) and human plasma butyrylcholinesterase (HuBuChE; IC50 = 14.8 +/- 1.1 microg/mL). Belladine inhibited HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 781 +/- 12.5 microM and 284.8 +/-4.2 microM, respectively.