Ecdysteroids in insects

We discovered that certain ecdysteroids can strongly sensitize multi-drug resistant (MDR) and susceptible cancer cell lines to chemotherapeutics [3]. Based on these results, a wide variety of chemical modifications of selected ecdysteroids have been performed in order to further extend and explore the available chemical space. Such modifications included base-catalyzed autoxidation, oxidative side-chain cleavage, oxime, oxime-ether and lactame formation, fluorination, and preparation of dioxolane rings. SAR for more than 120 compounds revealed that a C-20,22 side-chain cleavage together with introducing a 2,3-dioxolane moiety confers ecdysteroids a strong chemo-sensitizing activity against MDR cancer cell lines, without any detectable functional inhibition of drug efflux [4], which could lead to various side effects during possible in vivo applications. Based on our results, several promising lead compounds have been identified that can be further developed to be used in the treatment of MDR cancer.

Ecdysone is a steroidal prohormone of the major insect molting hormone 20-hydroxyecdysone , which is secreted from the prothoracic glands . Insect molting hormones (ecdysone and its homologues) are generally called ecdysteroids . Ecdysteroids act as moulting hormones of arthropods but also occur in other related phyla where they can play different roles. In Drosophila melanogaster , an increase in ecdysone concentration induces the expression of genes coding for proteins that the larva requires, and it causes chromosome puffs (sites of high expression) to form in polytene chromosomes. Recent findings in Chris Q. Doe lab have found a novel role of this hormone in regulating temporal gene transitions within neural stem cells. [1] Ecdysone and other ecdysteroids also appear in many plants mostly as a protection agent (toxins or antifeedants) against herbivorous insects. These phytoecdysteroids have been reputed to have medicinal value and are part of herbal adaptogenic remedies like Cordyceps , yet an ecdysteroid precursor in plants has been shown to have cytotoxic properties. [2] A pesticide sold with the name MIMIC has ecdysteroid activity, although its chemical structure has little resemblance to the ecdysteroids.

Ecdysteroids in insects

ecdysteroids in insects


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