Structural Factors of Annonaceous Acetogenins and Their Semisynthetic Analogues Related with the Toxicity on Spodoptera frugiperda

Toxic and nutritional effects of annonaceous acetogenins and their semisynthetic analogues on Spodoptera frugiperda were evaluated. Structural modification of the natural ACG, blocking the OH flanking THF with MOM, allowed us to suggest the mode of action of ACG in the membrane. Our study emphasizes the role of the flanking OH and acetyl groups of THF with the membrane hydrophilic polar head groups. They are essential structural factors in the ACG that facilitate the intermolecular interaction that dehydrates the membrane and makes it potentially toxic against Spodoptera frugiperda.

Insecticidal Effects of the Annonaceous Acetogenin Squamocin and the Acetogenin Fraction of Seeds of <i>Rollinia occidentalis</i>on Soybean and Corn Pests

A treatment based on the acetogenin fraction of the methanol extract of Rollinia occidentalis seeds was applied to soybean crops for three consecutive years. In relation to the control population, the treatment reduced the population of Anticarsia gemmatalis, Rachiplusia nu, Pseudoplusia includens, Loxostege bifidalis and Spodoptera frugiperda to 52% and 65% after 48 h of application at concentrations of 500 and 750 μg/mL respectively, while low toxic effects were detected on natural enemies. The extract treatment at 500 μg/mL and a solution of the annonaceous acetogenin, squamocin, at 50 and 100 μg/mL, were also applied to a corn field to produce 75%, 93% and 100% mortality rates on the population of S. frugiperda, respectively, after 72 h of application. In addition, damages caused by lepidopterans in treated crops were lower than those observed in non treated fields, evaluated by residual biomass. This statement is based on data from trials with the commercially available insecticides lufenuron and cypermethrin.

Insecticidal Activity of Annonaceous Acetogenins and Their Derivatives on <em>Spodoptera frugiperda</em>Smith (Lepidoptera: Noctuidae)

Background: Annonaceous acetogenins enclose a large number of biological activities, among which the insecticidal stands out. Methods: We report herein the biocide effects of natural acetogenins from Annona squamosa, A.?muricata and A. montana seeds: annonacin, cis-annonacin, cis-annonacin-10- one, asimicin, rolliniastatin-2, cherimolin-1, cherimolin-2, almu&ntilde;equin, and two β-OH acetogenins: laherradurin and itrabin on Spodoptera frugiperda Smith (Lepidoptera: Noctuidae). Also, some acetylated and methoxy methylated ACG derivatives were synthesized and evaluated: annonacin (3 OAc), annonacin (4 OAc), asimicin (3 OAc), rolliniastatin-2 (3 OAc), rolliniastatin-2 (MOM), laherradurin (3 OAc) and itrabin (3 OAc). Results: The natural acetogenin rolliniastatin-2 (100 μg·g-1 of diet) produced the most important toxic action causing 100% mortality of early instar larvae. Derivatization of ACG yielded compounds that produced nutritional alterations. The incorporation of rolliniastatin-2 (3 OAc) and rolliniastatin-2 (3 MOM) (100 μg·g-1) into the artificial diet of Spodoptera frugiperdadisplayed the strongest antifeedant effects causing marked decreasings in larval growth and adult lethal malformations. Conclusion: Natural acetogenins are promising metabolites for insect control. Derivatization of these compounds reduces their toxicity to early instar larvae.

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.

Eight new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa

Eight new annonaceous acetogenins, squamotin A–D(1–4), annosquatin IV–V(5 and 6), muricin O(7) and squamosten B(8), together with four known ones(9–12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1–9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.

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.

Atemoyacin A: A new bis-tetrahydrofuranyl annonaceous acetogenin from Annona atemoya H.

Atemoyacin A, a new annonaceous acetogenin was isolated from the alcoholic extract of the seeds of Annona atemoya Hort (Annonaceae). Its structure and relative configuration were elucidated on the basis of the spectral analysis.

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.