Activity-guided fractionation

In the remaining sections of this chapter, brief details of the experimental approaches to our separate projects on the discovery of novel plant-derived cancer chemotherapeutic agents and cancer chemopreventives will be provided in turn, with emphasis of the phytochemical aspects. A number of novel bioactive plant secondary metabolites will be presented that have been isolated via activity-guided fractionation techniques in our recent work on these two projects. 

Activity-guided fractionation of the bark of Shorea balangeran afforded vaticanols A (622), B (690) and G (624) as anti-babesial principles showing complete inhibition on the growth of Babesia gibsoni in vitro at a concentration of 25, 50 and 25 pg/mL, respectively [310]. 

This study showed that comparative NMR spectroscopic methods such as DANS can be used to dissect changes in small molecule production in response to genetic manipulation, and that this approach could complement or replace activity-guided fractionation for identifying biologically relevant small molecules. The primary benefit of DANS lies in the ability to quickly obtain structural information for metabolites that may represent good candidates for further evaluation in a specific biological context. 

A question of paramount concern relates to the bioassay systems that are utilized for selection of active lead materials and for the activity-guided fractionation that leads to the procurement of active principles. We currently describe bioassay systems that are suitable for the discovery of antitumor, antimalarial and antihepatitis B agents, emphasizing aspects of selectivity that are designed to promote the discovery of agents capable of mediating physiological responses with therapeutic efficacy. 

Recently, Kinghorn et al. [96] reviewed the anticancer agents discovered by activity-guided fractionation and they include seventy compounds from twenty-two plants. Only one lignan is cited in the review guaiacylglycerol-P-06 -(2-methoxy)cinnamyl alcohol ether isolated from Brucea javanica (Simaroubaceae) exhibited weak activity against the induction of cell differentiation of human promyelocytic leukemia (HL-60) cells [96,97],... 

Aimed at investigating taste enhancers in beef bouillon, taste activity-guided fractionation combined with the comparative taste dilution analysis led to the discovery of the presence of a sweet enhancing compound. Model Maillard reactions, spectroscopic and synthetic experiments revealed the previously unknown 1 - 1 -carboxyethyl)-5-hydroxy-2-... 

This fungus was identified as a Penicillium sp. by Dr. Gene Ford of the Department of Plant Pathology, Montana State University, and was deposited in the Agricultural Research Culture Collection (NRJ 21208). Penicillium sp. isolate HIRE produced a number of compounds which were isolated by either bioassay-guided or NMR activity -guided fractionation. Two novel bioactive metabolites are currently being characterized, but the isolation and identification of several other compounds will be described below. 

Kinghom, A.D. et al., Cancer chemopreventive agents discovered by activity guided fractionation a review, Curr. Org. Chem., 2, 597,1998. 

Cakir A, Mavi A, Yildinm A, Duru ME, Harmandar M, Kazaz C. (2003).Isolation and characterization of antioxidant phenolic compoimds from the aerial parts of Hypericum hyssopifolium L. by activity-guided fractionation. Journal of Ethnopharmacology, Vol. 87, pp. 73-83... 

Boligon AA, Kubica TF, Mario DN, de Bmm TF, Piana M, Weiblen R, et al. Antimicrobial and antiviral activity-guided fractionation from Scutia buxifoUa Reissek extracts. Acta Physiol Plant 2013 35(7) 2229-39. 

Su BN, Cuendet M, Farnsworth NR, Fong HHS, Pezzuto JM, Kinghom AD (2002) Activity-guided fractionation of the seeds of Ziziphus jujuba using a cyclooxygenase-2 inhibitory assay. Planta Med 68(12) 1125-1128... 

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