plate (YFM) assay.97 The results clearly demonstrated that most acetogenins have potent pesticidal properties. The SAR observed indicated that the compounds bearing adjacent bis-THF rings with three hydroxyl groups are the most potent. Bullatacin and trilobin gave the best activities against YFM with LC50 values of 0.1 and 0.67 mg/L or ppm (parts per million), respectively. Compounds showing LC50 values below 1.0 ppm in this assay are usually considered significant as new lead candidates for pesticidal development.

The biological properties of the Annonaceous acetogenins continue to attract the attentions of biochemists, biologists, botanists, chemists, entomologists, pharmacognosists, and phytochemists. Recent investigations indicate that the cytotoxic effects of Annonaceous acetogenins can thwart classical MDR in the adriamycin-resistant human mammary adenocarcinoma (MCF-7/Adr) cell model. Thorough in vivo studies are now needed to support the results proposed from the above-mentioned in vitro work. The pesticidal properties of the Annonaceous acetogenins make them well-suited for the control of insect pests including cockroaches in an urban setting. A concentration of only 1000 ppm in a dietary formulation produced high mortality and was associated with delays in nymphal development of second and fifth instars of both susceptible and resistant German cockroaches. Further research is now necessary to develop refined pesticidal strategies for the inclusion of such highly effective and environmentally friendly formulations to control pests. To meet the demands of further in vitro and in vivo pharmacological evaluation, we especially encourage the synthesis of those selectively cytotoxic acetogenins that are rare in nature, e.g., squamotacin, which is specific for prostate tumor cells; synthetic targets can also include a wide diversity of analogues based on the SAR generalizations, as determined using the natural compounds, as mentioned above. The high potency, selectivity, wide chemical and biological diversity, and effectiveness of these compounds against resistance could well make them become the next class of useful natural antitumor and pesticidal agents.

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1000ppm in a dietary formulation produced high mortality and was associated with delays in nymphal development of second and fifth instars of both susceptible and resistant German cockroaches. Further research is now necessary to develop refined pesticidal strategies for the inclusion of such highly effective and environmentally friendly formulations to control pests. To meet the demands of further in vitro and in vivo pharmacological evaluation, we especially encourage the synthesis of those selectively cytotoxic acetogenins that are rare in nature, e.g., squamotacin, which is specific for prostate tumor cells; synthetic targets can also include a wide diversity of analogues based on the SAR generalizations, as determined using the natural compounds, as mentioned above. The high potency, selectivity, wide chemical and biological diversity, and effectiveness of these compounds against resistance could well make them become the next class of useful natural antitumor and pesticidal agents.

Acknowledgment. The studies described in this review carried out at Purdue University were supported, in part, by ROI Grant No. CA 30909 from the National Cancer Institute, National Institutes of Health. F.Q.A acknowledges generous financial support from Mrs. Marilyn Cochran of San Angelo, TX, and X-XL. acknowledges fellowship support from the Purdue Research Foundation.

Position 4 10 13 14 17 18 1H (δ) 3.83 m 3.64 m 3.45 m 3.82 m 3.82 m 3.41 m 13C (δ) 69.9 71.6 74.0 82.6 82.7 74.3

1H (δ) 3.83 m 3.64 m 3.45 m 3.82 m 3.82 m 3.41 m13C (δ) 69.9 71.6 74.0 82.6 82.7 74.3

White amorphous powder. [α]D: +16.1° (c Q056, CHCl_{3}). UV (λmax, MeOH, nm): 208 (log ε 3.52). IR (νmax, film, cm^{-1}): 3418, 2919, 2850, 2359, 1732, 1468, 1319, 1206 MS: EIMS m/z 351, 333, 325, 307, 281, 263, 255, 241, 223, 205, 141. NMR: 1H NMR (500MHz, CDCl_{3}), 13C NMR (125MHz, CDCl_{3}). Derivatives: peracetate (^{1}H NMR), per-MTPA esters (^{1}H NMR). Biological activities (μg/mL): BST LC50 2.0 × 10^{-1}, A-549 ED50 3.9 × 10^{-1}, MCF-7 ED50 1.7, HT-29 ED50 1.5, A-498 ED50 1.5, PC-3 ED50 2.1 × 10^{-1}, PAC-2 ED50 2.6 × 10^{-2}. Source: Goniothalamus giganteus, stem bark. gonioneninone (reported as a cis and trans mixture)108 (C37H66O 7, MW622)

Position 10 13 14 17 18 21 22

1H ( \delta ) 3.63 m 3.45 m 3.83 m 3.83 m 3.43 m 5.34 ddd 5.40 ddd

13C ( \delta ) 71.5 74.3 82.6 82.6 73.5 128.9 130.8

Position 10 13 14 17 18 21 22

1H ( \delta ) 3.63 m 3.45 m 3.83 m 3.83 m 3.43 m 5.34 ddd 5.40 ddd

13C ( \delta ) 71.5 74.3 82.6 82.6 73.5 128.9 130.8

White amorphous powder. [α]D: +160° (c Q05, CHCl_{3}). IR (νmax, film, cm^{-1}): 3415, 2922, 2851, 1766, 1717, 1466. MS: EIMS m/z 351, 333, 323, 281, 263, 253, 235, 241, 223, 205, 141. NMR: 1H NMR (500MHz, CDCl_{3}), 13C NMR (125MHz, CDCl_{3}). Derivatives: peracetate (^{1}H NMR), per-MTPA esters (^{1}H NMR). Biological activities (μg/mL): BST LC50 < 3.0 × 10^{-1}, A-549 ED50 1.8, MCF-7 ED50 3.7, HT-29 ED50 2.9, A-498 ED50 2.2, PC-3 ED50 1.5, PAC-2 ED50 4.5 × 10^{-2}. Source: Goniothalamus giganteus, stem bark.