A Semi-Field Approach to Testing Botanical Insecticides. Effects of Natural and Analogues Annonaceous Acetogenins on <i>Spodoptera frugiperda</i>Smith (Lepidoptera: Noctuidae)

Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. Spodoptera frugiperda is a pest that affects corn crops among others and has a great capacity to develop resistance to traditional insecticides, which represents sufficient reasons for the search for new alternatives for their control. The objective of this study was to determine the appropriate concentration and screening new natural insecticides against second instar larvae of S. frugiperda, under glasshouse conditions on Zea mays L. Natural products such as annonaceous acetogenins and some acetylated and methoxy methylated ACG derivatives and the commercial product Lambda-cyhalotrin (LC) were evaluated. The percent mortalities of S. frugiperda larvae in glasshouse conditions were recorded after 24, 48 and 72 h of treatment application. The results showed that the acetogenins tested were significantly (P < 0.05) different in relation to pest mortality than untreated check. After 72 h of treatment application the highest percent mortalities were obtained with the mixture of two natural products, rolliniastatin-2 (5) (100 μg/mL) + squamocin (6) (100 μg/mL) + LC (50 μg/mL) that proved the most effective and gave (100%), while rolliniastatin-2 (5) at 100 μg/mL alone, gave lowest percent mortality (65%), followed by squamocin (6) at 100 μg/mL (55%) and LC at 50 μg/mL (30%). The acetylated and methoxy methylated ACGs derivatives caused very low mortality (25% - 35%). It is recommended the mixture as a management option of S. frugiperda as a component of integrated pest management. The results allow us to infer that the addition of natural ACGs synergizes the insecticidal activity of the commercial product. Finding a new ecological alternative for insect control.

A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005

AA005(1),a potent anticancer mimicking molecule of natural Annonaceous acetogenin,features a central C_(2)-symmetric triglycol moiety and three stereogenic centers.To support ongoing animal studies,a scalable 10-step synthesis of AA005(1) has been studied,optimized and accomplished in this work,starting from commercially available economic materials ethylene glycol and(R)-epichlorohydrin.A regio-and stereo-controlled BF_(3)·Et_(2)O-promoted epoxide opening of(R)-epichlorohydrin with ethylene glycol was investigated,optimized and successfully applied to the scalable preparation of the crucial fragment 6 a with C_(2)-symmetry.Further successive epoxide openings elaborated both two side chains and the whole skeleton with proper nucleophiles and electrophiles.Comparison and optimization of the reaction sequences finally led to completion of a new multi-gram synthesis ofAA005(1) with satisfactory enantiomeric and diastereomeric purity.

Anticancer Effect of Total Annonaceous Acetogenins on Hepatocarcinoma

Objective： To confirm the anticancer effect of total annonaceous acetogenins （TAAs） abstracted from Annona squamosa Linn. on human hepatocarcinoma. Methods： The inhibitory effect of TAAs was demonstrated in H,,-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration （IC50） on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis. Results： The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 μg/mL （15.13-26.61 μg/mL）. Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs. Conclusion： TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.

Synthesis of a Mimicking Hybrid of Annonaceous Acetogenin with Steroid for Antitumoral Activity Investigation

The first example of annonaceous acetogenin-steroid hybrid was synthesized for the antitumoral study.