Anhydride modified cantharidin analogues: synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity

Inhibition of Protein Phosphatase 2A Enhances Cytotoxicity and Accessibility of Chemotherapeutic Drugs to Hepatocellular Carcinomas

“…1D and 2D) implied an activity-based rather than expression-based inhibition of PP2A by LB-100. LB-100 is in the family of modified cantharidins that are demonstrated to inhibit PP2A by direct interaction with the enzyme as described previously (13). These cantharidin-related structures are assumed to bind to a pocket needed for activity on the enzyme as has been demonstrated for naturally occurring but structurally unrelated molecules okadaic acid, microcistin, and fostriecin (45).…”

“…Cantharidin, a natural product isolated from Mylabris sidae, and several cantharidin derivatives have PP2A inhibitory activity, and have been used as anticancer agents for decades (10)(11)(12)(13). The mechanism by which PP2A exerts anticancer activity is believed to be abrogation of cell-cycle checkpoints and induction of mitotic catastrophe (14).…”

Synthesis of Novel Lipophilic N-Substituted Norcantharimide Derivatives and Evaluation of Their Anticancer Activities

“…Subsequent hydrogenation of 5 (H 2 , 10% Pd/C) using a modified procedure of McChuskey et al [33] provided the starting norcantharidin (2) in excellent yield, which then was employed as the substrate for the synthesis our designed derivatives. First, norcantharidin (2) was reacted with hydroxylamine hydrochloride in the presence of sodium methoxide in dry methanol at room temperature to produce N-hydroxynorcantharimide (6), according to a previous report.…”

“…Lastly, to enhance its anticancer activity, various structural modifications of norcantharidin had been studied and mixed results had been reported. For instance, an analog of norcantharidin was shown to inhibit the function of protein phosphatase and had anti-proliferative activity while others bioactivities were erased [33][34][35][36][37][38][39]. In the previous study, it has been reported that norcantharimide analogues bearing a long alkyl chain at N-position may have enhanced bioavailability and transportability through cell membrane.…”

Synthesis, DNA-binding and antiproliferative activity of N-(Nitrogen heterocyclic) norcantharidin acylamide acid

“…Great interest is currently being focused on developing natural products due to their interesting anticancer activities [1][2][3][4]. Cantharidin has been used as a medicinal agent and shown to be active in cervical, leukaemia, bladder and colon cancer cell lines [5][6][7]. Although cantharidin is cytotoxic to cancer cells and stimulatory on the bone marrow, the renal toxicity of this drug has prevented its use in mainstream oncology.…”