Showing papers by "Susan L. Morris-Natschke published in 2018"

Biologically active quinoline and quinazoline alkaloids part I

Abstract: Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively. In this review, we survey the literature on bioactive alkaloids from these two classes and highlight research achievements prior to the year 2008 (Part I). Over 200 molecules with a broad range of bioactivities, including antitumor, antimalarial, antibacterial and antifungal, antiparasitic and insecticidal, antiviral, antiplatelet, anti-inflammatory, herbicidal, antioxidant and other activities, were reviewed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.

Taburnaemines A–I, Cytotoxic Vobasinyl-Iboga-Type Bisindole Alkaloids from Tabernaemontana corymbosa

Abstract: Nineteen vobasinyl-ibogan-type bisindole alkaloids, including nine new compounds, taburnaemines A–I (1–9), were isolated from the twigs and leaves of Tabernaemontana corymbosa. The structures and absolute configurations of the new alkaloids were determined by a combination of MS, NMR, and ECD analyses. Alkaloids 1–5 contain a rare 1,3-oxazinane moiety in the vobasinyl unit, while 6 has an uncommon 1,3-oxazolidine moiety in the iboga unit. The absolute configurations of alkaloid 1 and the known alkaloid tabernaecorymbosine A (10) were confirmed by single-crystal X-ray diffraction analysis. All of the bisindole alkaloids, except 2 and 16′-decarbomethoxytabernaecorymbosine A (14), showed antiproliferative activity (IC50 2.6–9.8 μM) against several human cancer cell lines, including A-549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrug-resistant KB cells. The preliminary structure–activity relationship correlations are also discussed.

Cytotoxicity, Hemolytic Toxicity, and Mechanism of Action of Pulsatilla Saponin D and Its Synthetic Derivatives

Abstract: The strong hemolytic toxicity of pulsatilla saponin D (1, HD50 6.3 μM) has hampered its clinical development as an injectable anticancer agent. To combat this challenge, 17 new derivatives of 1 with ring C, C-28, or C-3 modifications were synthesized and evaluated for cytotoxicity against several selected human tumor lines, as well as for hemolytic toxicity against rabbit erythrocytes. Structure–activity relationship (SAR) and structure–toxicity relationship (STR) correlations were also elucidated. Compared to the lead compound 1, the hemolytic activity of all 17 derivatives dropped dramatically. Notably, compound 14 exhibited significant cytotoxicity toward A549 human lung cancer cells (IC50 2.8 μM) in a dose-dependent manner without hemolytic toxicity (HD50 > 500 μM). Molecular studies indicated that 14 induced typical G1 cell cycle arrest and apoptosis in A549 cells, and Western blot assays suggested that both intrinsic and extrinsic apoptosis pathways were activated by 14. Collectively, compound 14 ma...

Chemical Structures and Biological Activities of Limonoids from the Genus Swietenia (Meliaceae).

Abstract: Swietenia is a genus in the plant family Meliaceae. This genus contains seven to eight known species, found in the tropical and subtropical regions of the Americas and West Africa. Thus far, more than 160 limonoids have been isolated from four species of the genus Swietenia. Limonoids are rich in structure type and biological activity, and these compounds are the main active components in the Swietenia species. This paper will give a comprehensive overview of the recent phytochemical and pharmacological research on the terpenes from Swietenia plants and encourage further drug discovery research.

Kleinhospitine E and Cycloartane Triterpenoids from Kleinhovia hospita

Abstract: A novel cycloartane triterpenoid alkaloid, kleinhospitine E (1), six new cycloartane triterpenoids (2–7), three known cycloartane triterpenoids (8–10), and taraxerone (11) were isolated from a methanol extract of Kleinhovia hospita Their structures were elucidated by 1D- and 2D-NMR spectroscopy as well as HRMS analysis The absolute configurations of all isolated compounds were determined from their ECD spectra by comparison with theoretical values Kleinhospitine E (1) is the first cycloartane alkaloid possessing an unusual γ-lactam with an oxopropylidene side chain Compounds 2, 3, and 6 were assigned as cycloartane triterpenoids with a 9α,10α-cyclopropyl ring, which is found rarely among naturally occurring compounds, while 4 and 5 were established as isomers of compound 3 containing a 21,23-diacetal side chain Biological evaluation revealed that compounds 4 and 9 exhibited more potent antiproliferative activities against a multidrug-resistant tumor cell line compared with its parent chemosensitive c

Salvisertin A, a New Hexacyclic Triterpenoid, and Other Bioactive Terpenes from Salvia deserta Root

Abstract: Using various chromatographic methods, a new hexacyclic triterpenoid, 2β,3β,24β-trihydroxy-12,13-cyclotaraxer-l4-en-28oic acid (1), together with ten known compounds, 2α,3α,23-trihydroxyurs-12,20(30)-dien-28oic acid (2), 6,7-dehydroroyleanone (3), horminone (4), 7-O-methylhorminone (5), sugiol (6), demethylcryptojaponol (7), 14-deoxycoleon U (8), 5,6-didehydro-7-hydroxy-taxodone (9), ferruginol (10), and dichroanone (11), were isolated from the roots of Salvia deserta. Their structures were identified on the basis of spectroscopic analysis and comparison with the reported data. The individual compounds (1, 3 - 8) were screened for cytotoxic activity, using the sulforhodamine B bioassay (SRB) method. As the results, Compounds 3, 5, and 8 showed cytotoxic potency against A549, MDA-MB-231, KB, KB-VIN, and MCF7 cell lines with IC50 values ranging from 6.5 to 10.2 μm.