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Wijeratne, E. M. K./ B. P. Bashyal/ M. X. Liu/ D. D. Rocha/ G. M. K. B. Gunaherath/ J. M. U'ren/ M. K. Gunatilaka/ A. E. Arnold/ L. Whitesell/ A. A. L. Gunatilaka 2012: Geopyxins A-E, ent-kaurane diterpenoids from endolichenic fungal strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: Structure-activity relationships of geopyxins and their analogues. - Journal of Natural Products 75(3): 361-369. [RLL List # 226 / Rec.# 33661]
Abstract: Four new ent-kaurane diterpenoids, geopyxins A-D (1-4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3. The structures of 1-6 were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher's ester method. Methylation of 1-3, 5, and 6 gave their corresponding methyl esters 7-11. On acetylation, 1 and 7 yielded their corresponding monoacetates 12 and 14 and diacetates 13 and 15. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds 2, 7-10, 12, 14, and 15 showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds 7-9, 14, and 15 were found to activate the heat-shock response at similar concentrations. From a preliminary structure-activity perspective, the electrophilic ?,?-unsaturated ketone carbonyl motif present in all compounds except 6 and 11 was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation. © 2012 The American Chemical Society and American Society of Pharmacognosy.

URL: http://dx.doi.org/10.1021/np200769q

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