Quassinoids biological activities

Quassinoids —The antileukaemic activity of some quassinoids has revived interest in this group. Three new biologically active compounds have been isolated. Quassimarin (118) occurs in Quassia amara with the inactive simalikalactone D (129) 86 Bruceoside A, from Brucea javanica, is the glucoside (120). The third... 

Quassinoids are bitter components produced by members of the Simaroubaceae. They exhibit diverse biological activities including anticancer, antimalarial, insecticidal, and phytotoxic activities. Ailanthone (26), chaparrinone (27), and other quassinoids, along with indole alkaloids, contribute to the invasiveness of the Chinese tree tree-of-heaven Alianthus altissima Swingle), in Europe.15... 

Quassinoids.—The structure of soulameolide (108), a new C25 quassinoid from Soulamea tomentosa, has been established by X-ray analysis.The search for biologically active compounds continues. Undulatone (109) from Hannoa undulata, 6a-tigloyloxychapparinone (110) from Ailanthus integrifoliaj and 6a-senecioylchapparinone (111) from Simaba multiflora have antileukaemic... 

Figure 5 Biological activities associated with quassinoids, from Simaroubaceae species, may not be linked to a common mechanism of action/ Different testing procedures have indicated insecticidal activity for quassin, anticancer activity for quassimarin (also present in Quassia amara) and antimalarial activity for simalikalactone-D/...

QUASSINOIDS STRUCTURAL DIVERSITY, BIOLOGICAL ACTIVITY AND SYNTHETIC... 

For such review the collected data are from 1985 up to 2004 focusing on all the isolated and identified quassinoids, as well as, the main biological activities and some synthetic processes. 

The review containing structural data, biological activities and chemical modifications of quassinoids was published last decade with references up to September 1984 by Polonsky [1]. According to Simao et al. [2] more than two hundred quassinoids were isolated and identified until December 1984. 

Quassia amara Wood is still widely used in traditional medicine and some quassinoids and quassinoid glycosides isolated from Quassia have received renewed attention due to their biological activity as potential antitumor agents [78]. 

ABSTRACT This review covers various bioactive quassinoids in Simaroubaceous plants, which show cytotoxic antitumor, anti-tumor-promoter (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, insect antifeedant, and other biological activities. Stability of quassinoids, the preparation of their derivatives, and their biological activities are also discussed. 

In a previous paper [1], we reviewed the isolation of quassinoids, alkaloids, and fatty acids from Simaroubaceous plants during the period 1972-1988 and discussed their biological activities, such as antitumor, antimalarial, and anti-inflammatory agents as well as insect antifeedants, amoebicides, and herbicides. This review will add new quassinoids isolated from Simaroubaceous plants from 1988 onwards and their biological activities, for example, antitumor, anti-tumor-promotor (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, and insect antifeedant activities. Furthermore, the stability of quassinoids, lower activities of degradation products, and the synthesis of fluorinated quassinoids are also described. 

Limonoids (Tetranortriterpenoids) Quassinoids (Decanortriterpenoids) Pentanortriterpenoids Chemosystematic Studies Biological Activity Antifeedant Activity Medicinal and Antitumor Properties Limonin in Orange Juice References... 

Polonsky, J., Chemistry and biological activity of the quassinoids, in Chemistry and Chemical Taxonomy of the Rutales (P. G. Waterman and M. F. Grundon, eds.), 247-266, Academic Press, London, 1983. 

Quassinoids have attracted much attention due to the wide spectrum of biological activities that they display, viz., antimalarial, antifeedant, anti-inflanunatory, antiulcer, antipyretic, antifertility, antileukemic, cytotoxic activities, and induction of murine stem cell differentiation which have been widely reported [54-59]. We have demonstrated that quassin is a potent immunomodulatory tool that efficiently controls the estabhshment of leishmanial parasite within the host macrophages [60]. Our contention was that quassin could be used as a potential inununomodulator to generate the required immunity not only for the treatment of leishmaniasis but also for the treatment of other chronic infectious diseases. Subsequently, we had shown that both quassin and neoquassin can be used along with artesunate (a derivative of artemisinin) as combinatorial therapy against malaria [61]. 

Guo Z, Vangapandu S, Sindelar RW, Walker LA, Sindelar RD (2005) Biologically active quassinoids and their chemistry potentianl leads for drug design. Curr Med Chem 12 173-190... 

The quassinoids are renowned for two major pharmacological activities their anticancer and their antiplasmodial potential. Looking more closely at the evolution of publications on these two major classes of biological activities, we obtained the curves shown in Fig. 125.8. The linear regressions represented here demonstrate an early interest in their anticancer activities (1970-1985) and the increasing interest in their antimalarial potential (since 1990). Subsequent sections will therefore focus on these two pathologies. 

Many other activities were also recorded for quassinoids insecticidal, antiviral, anti-inflammatory, and so on. These were extensively reviewed by Guo et al. and Almeida et al. [47,109], thus justifying the interest in drawing parallels between the biological activities identified in vitro or in vivo for these molecules and the traditional uses of species from which they come. 

Curcino Vieira IJ, Braz-Filho R (2006) Quassinoids structural diversity, biological activity and synthetic studies. In Atta-ur-Rahman FRS (ed) Bioactive natural products. Elsevier, Amsterdam, p 433... 

Elkhateeb A, Yamasaki M, Maede Y, Katakura K, Nabeta K, Matsuura H (2008) Antibabesial quassinoids from the fruits of Brucea Javanica. Nat Prod Comm 3 145 Almeida MMB, Arriaga AMC, dos Santos AKL, Lemos TLG, Braz-Filho R, Vieira DC (2007) Occurrence and biological activity of quassinoids in the last decade. Quim Nova... 

The most interesting of the varied types of triterpenes from the point of view of biological activity are the quassinoids. They exhibit antiamoebic (353), antimalar-ial (1020), antimitotic (287), antitumor (59, 403, 950), and cytotoxicity (59, 821, 823) effects. Bruceantin, 29, is being developed as a potential cancer chemotherapeutic agent and is currently in Phase 1 clinical trials in the United States (950). 

More than ten years have elapsed since the publication of a comprehensive review on the quassinoids, the bitter principles of the Simaroubaceae family (80). Interest in these terpenoids has increased enormously in recent years due in part to the finding of the American National Cancer Institute in the early 1970s that these compounds display marked antileukemic activity. Furthermore, a wide spectrum of other biological properties for the quassinoids has been discovered and studies on chemical modifications of inactive members to yield biologically active ones were undertaken. New structures have been established also and numerous synthetic approaches have been developed which include the total synthesis of the parent compound, quassin (p. 250) and also that of castelanolide (p. 253). 

The recently found quassinoids will be presented according to their basic skeleton and when relevant comment will be made on the specific biological activity of the individual compounds. 

Kupchan, S. M., J. A. Lacadie, G. A. Howie, and B. R. Sickles Structural Requirements for Biological Activity among Antileukemic Glaucarubolone Ester Quassinoids. J. Med. Chem. 19, 1130 (1976). 

Many activities in quassinoid area were due partly to the fact these natural products possess a wide spectrum of biological properties including in vivo antileukemic, antiviral, antimalarial, antifeedant, and amoebicidal activity. 

The broad spectrum of biological properties, especially the antileukemic activity, of the quassinoids as well as their highly oxygenated carbon backbone coupled with the stereochemical features have stimulated a great deal of synthetic activity. A number of approaches towards their synthesis have been described, but success at total synthesis has so far been limited to only two published accounts (vide infra). 

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