Kasey Wood

Synthesis of novel isoflavene-propranolol hybrids as anti-tumor agents.

Isoflavene-propranolol hybrid molecules were developed as potentially novel anti-tumour agents. Isoflavene itself has potent anti-cancer activity while propranolol can enhance anti-proliferative and anti-angiogenic properties of 5-fluorouracil and paclitaxel. The hybrids were produced via nucleophilic addition of substituted amine groups to a dioxiran intermediate, which was in turn generated from the Williamson-type reaction of isoflavene with (±)-epichlorohydrin. These analogues were tested in anti-cancer cell viability assays against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines, and were found to exhibit potent anti-proliferative activities. These compounds also displayed anti-angiogenic and anti-proliferative effects in HMEC-1 human microvascular endothelial cell lines. Notably, the most potent hybrid molecules synthesized in this work showed enhanced potency against cancer cell lines compared to either isoflavene or propranolol alone, while retaining significant selectivity for cancer cells over MRC-5 normal lung fibroblast cells.

Acid-Catalyzed Reactions of 3-Substituted-4,6-dimethoxyindoles with Ketones

Activated 3-substituted-4,6-dimethoxyindoles undergo acid catalyzed condensation with acetone and acetophenones in the presence of hydrochloric acid to give pyrrolo[a]indoles. Mixed pyrrolo[a]indoles can similarly be formed using a 1:1 mixture of two indoles. The reaction was found to be sensitive to acidity, with a 3:2 spiro condensation product being preferentially formed in the presence of p-toluenesulfonic acid.

Oxidative Dimerisation of Isoflavones: Synthesis of Kudzuisoflavone A and Related Compounds

Kudzuisoflavone-A was successfully synthesised via oxidative dimerisation of daidzein in the presence of cuprous chloride. Appropriately substituted isoflavones also undergo regioselective oxidative dimerisation when treated with thallium trifluoroacetate to give novel 6′,6′″-biisoflavones in good yield. A rationale for the regioselectivity is proposed.