Inhibition of juvenile hormone

Brevioxime 25 is a natural product isolated from Penicillum brevicompactum and displays in vitro inhibition of juvenile hormone biosynthesis. Two different synthetic approaches have been described for this molecule. Different authors carried out the cyclization of the unsaturated ketoamide 409 in the presence of nitrosyl chloride that directly produced cyclization and led to the oxime <2001SL257, 2001T8699>. Starting from the same... 

At the heart of any search for bioactive molecules is the need for effective bioassays. Several bioassays have been developed for the identification of compounds with anti-juvenile hormone (AJH) activity. The most common of these AJH bioassays involves the treatment of young larvae or nymphs with the potential AJH by incorporation into the diet or contact application, and then waiting for several days (or, in some cases, weeks) for precocious development (or other AJH response) to occur ( 1, ). Alternatively, AJH activity can be determined using jri vitro assays such as corpora allata cultures or epidermal cell cultures to monitor for inhibition of juvenile hormone (JH) biosynthesis (3-6) or blockage of the JH induced inhibition of pupal commitment (7), respectively. 

Figure 3. Isolation of allatostatin 4 from CA by HPLC on a Cg column. A) Synthetic allatostatin 4 eluted with an acetonitrile gradient (dashed line). B) Extract of 6000 pairs of CA (collected from a C column in the region of allatostatin 4) run immediately following and with the same gradient as that in A. The histogram shows the inhibition of juvenile hormone (JH) synthesis of fractions eluting at the same time and adjacent to allatostatin 4. Fractions were tested on 3-4 CA at 100 CA equiv./CA. Dots indicate SEM.

Herbert Oberlander coordinated the section that features chapters on sac-specific selection using chimeric genes potential applications of neuroendocrine research to insect control insect cuticle structure and metabolism molecular aspects of immune mechanisms in insects molecular genetics of nerve insensitivity resistance to insecticides and inhibition of juvenile hormone esterase by transition-state analogs. 

Inhibition of Juvenile Hormone Esterase by Transition-State Analogs... 

Muthukrishnan J, Seifert K, Hoffmann KH, Lorenz MW (1999) Inhibition of juvenile hormone biosynthesis in Gryllus bimaculatus by Glycosmis pentaphylla leaf compounds. Phytochemistry 50 249-254... 

Similarly, the experiments of Matolcsy et al. (1974a 1974b 1975), in which several metabolite analogues of mevalonic acid and homomevalonic acid have been tested for anti-juvenile action, were unsuccessful. Support for the rationale that these metabolite analogues would block the formation of juvenile hormone at the mevalonate level was provided by the successful inhibition of cholesterol biosynthesis by mevalonate analogues in humans. Yet, a fluorinated mevalonate analogue, 4-fluoromethyl-4-hydroxy-tetrahydro-2H-pyran-2-one (FMev, 72) was found to act as a potent inhibitor of JH biosynthesis by Quistad and co-workers... 

Trifluoromethyl ketones (TFKs) have been found to inhibit various hydrolytic enzymes (1-6 ). Series of aliphatic and aromatic trifluoromethyl ketone sulfides (7-10 ) proved to be exceptionally powerful inhibitors of insect juvenile hormone esterase (JHE), an enzyme of key importance in insect metamorphosis. The trifluoroketone moiety is believed to behave as a transition state mimic (11,12) of juvenile hormones (JHs), substrates of the enzyme. The /3 sulfur atom is anticipated to mimic the a-/3 double bond present in all natural JH substrates. In earlier structure-activity relationship (SAR) studies (7,11) clear correlation was found among the molar I50 values of these compounds against JHE and the calculated molar refractivlty of the inhibitors. 

Biological activity P. are toxic to the corpora allata of insects and directly inhibit thereby the biosynthesis of juvenile hormones, and thus the larvae prematurely develop into pupa (Latin praecox=premature). In adults, egg ripening and thus the ability to reproduce is principally affected. The synthetic, so-called P. Ill (proallatocidin, 6-ethoxy-7-methoxy-2,2-dimethyl-2//-1-benzopyran), C,4H,g03, Mr 234.30, oil, bp. 109°C (13 Pa), has a 10-fold stronger activity than P. 11. ... 

Muthukrishnan et al. [47] discovered that the EtOAc fraction of Glycosmis pentaphylla leaf extract inhibits the juvenile hormone 111 biosynthesis in vitro of corpora allata from 3-day-old females of the field cricket Gryllus bimaculatus. The bioactive compound responsible for this activity was identified as the quin-azolone alkaloid arborine. This alkaloid also exhibited larvicidal activity against the mosqirito. 

Esterases of the Juvenile Hormone of Insects Many works have been dedicated to the inhibition of esterases of the juvenile hormone of insects. The purpose of these works is to control insect populations by ehminating their metamorphosis. Among the numerous trifluoromethyl ketones that have been synthesized, thioalkyl derivatives of trifluoroacetone have been shown to be the most active ones. Curiously, the corresponding alcohols are also excellent inhibitors. Trifluoromethyl ketones can also inhibit other insect esterases antenna esterases and esterases that are involved in the release of pheromones (Figure 7.33). The inhibition of these latter ones can also be interesting for insect control purposes. 

The mandibular organ-inhibiting hormone of the crab Cancer pagurus produces two neurohormones that inhibit the secretion of methyl famesoate, which is thought to function as the juvenile hormone in crustaceans 357... 

---