Structure−Antifeedant Activity Relationship of Clerodane Diterpenoids. Comparative Study with Withanolides and Azadirachtin

Abstract

A structure-antifeedant activity relationship (SAR) study of clerodane diterpenoids was carried out. Attention was focused on the feeding-deterrent activities exhibited toward Tenebrio molitor by clerodane diterpenoids and withanolides. Azadirachtin was chosen as a reference compound. SAR studies on the clerodane compounds indicate that the stereoelectronic factors are more important than the hydrophobic aspects as determinants of antifeedant activity. A furan ring in the side chain and a carbonyl alpha,beta-unsaturated (or spiro-epoxide) group appear to be indispensable for the biological response. A conformational study indicate that the optimum interatomic distance between these moieties is a range between 9.5 and 10.5 A. In addition, a similar stereoelectronic response was found among withanolides and azadirachtin. On the basis of these results it is reasonable to imagine a closely related chemical mechanism for these compounds.

Withanolides and Related Steroids

“…Acetylcholinesterase (AChE) inhibitors activate central cholinergic function by increasing the acetylcholine levels in the brain. Bracteosins A (206), B (207), and C (208), isolated from Ajuga bracteosa (108), and withanolide A (504) and withaferin A (1) from W. somnifera, were moderate inhibitors of AChE and BChE (butyrylcholinesterase) (11). Molecular docking studies indicated that all compounds are imbedded in the aromatic gorge of AChE.…”

Gênero Baccharis (Asteraceae): aspectos químicos, econômicos e biológicos

“…Esta toxicidade foi constatada apenas nos neo-clerodanos contendo um grupo hidroxila livre em C-18 50 . Outros diterpenóides clerodanos das espécies B. rethinoides, B. triangularis, B. artemisioides e B. crispa apresentaram atividade inseto repelente e "antifeedant" (inibição da vontade de se alimentar) 37,51 . O diterpeno clerodano dilactônico [11] de B. trimera apresentou efeito vasorelaxante para a musculatura lisa vascular em ratos 52 .…”

Withanolides from Aureliana fasciculata var. fasciculata

“…The isolation and synthesis of withanolides have attracted great interest due to their diverse biological activities such as anti-inflammatory [11], antimicrobial [12], antitumoral [13] [14], antistress [15], antiulceral and hepatoprotective [16], antiparasitical [17], immunomodulatory [18], and insect-antifeedant properties [19]. Recently, it has been reported that these compounds exhibit inhibitory activities against cyclooxygenase-1 (COX-1) and -2 (COX-2) [20], acetylcholinesterase, and butyrylcholinesterase enzymes [21], and induction activity on quinone reductase [14] [22].…”

“…The HÀC(6) H-atom signal appeared as a broad singlet; therefore, the A/B ring conformation should be cis. On the other hand, the NOESY correlations observed between HÀC(9) and HÀC(2), Me (19) and HÀC (8) (27) (20)) in the HMBC spectrum (Fig. 2), suggested that the neighboring C (20) (26), respectively, in the 13 C-NMR spectrum ( Table 2), indicated the presence of the dimethyl a,b-unsaturated lactone side chain of the withasteroids [1].…”