Lysosome and HER3 (ErbB3) Selective Anticancer Agent Kahalalide F:  Semisynthetic Modifications and Antifungal Lead-Exploration Studies

Abstract

Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.

Antifungal Activity of Organic and Aqueous Extractions in Plakobranchus ocellatus (Gastropoda: Sacoglossa) against Candida albicans, C. parapsilosis and C. glabrata

“…They are often well camouflaged with the help of colors being derived from associated chloroplasts of algae which they feed (Shenai-Tirodkar et al, 2012). Elysia, a genus included in family Plakobranchidae reported to accumulates bioactive compounds (Ashour et al, 2006) which sequestered from green algae with strong antifungal effects (Shilabin et al, 2007). Plakobranchus ocellatus (van Hasselt, 1824) also stores huge numbers of bright green chloroplasts in ridges hidden from view beneath the parapodial flaps, under a symbiotic relationship.…”

ErbB3 expression predicts sensitivity to elisidepsin treatment: in�vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines

“…The mechanism of action of this compound remain poorly understood, although several targets have been proposed to be involved in the cellular response to elisidepsin treatment, such as fatty acid containing ceramides, FA2H, lysosomes, lipid rafts and epithelial growth factor receptors (10,12,22,23). Although elisidepsin could interact with the lipid bilayer, it is unlikely that it will form pores because the molecule is too small to span the whole length of the lipid bilayer.…”

Marine Peptide Secondary Metabolites

“…No less than 143 new KF analogs have been obtained by the groups of Hamann (Shilabin et al, 2007) and Albericio (Jim enez et al, 2008). To resume these studies, the three parts of KF -the depsipeptide ring, the side chain, and the aliphatic moiety -are considered separately.…”