ABSTRACT
A series of cationic lipo-benzamide compounds with varying lengths of hydrocarbon chains (C2M-C18M) were evaluated for anti-Candida activity. Four compounds harbouring 8-11 hydrocarbon chains demonstrated concentration-dependent inhibition of fungal cell growth with Minimum Inhibitory Concentration (MIC) of ≤6.2⯵gâ¯ml-1. The most active compound (C9M) inhibited growth of both Candida albicans and non-albicans strains and is equally active against pairs of azole sensitive and resistant clinical isolates of C. albicans. Compound C9M also inhibited different stages of Candida biofilms. Scanning Electron Microscopy (SEM) of Candida cells after C9M treatment was also done and no significant cell lysis was observed. Hemolysis assay was performed and only 2.5% haemolysis was observed at MIC concentration.
Subject(s)
Alkanes/pharmacology , Antifungal Agents/pharmacology , Biofilms/drug effects , Candida albicans/drug effects , Alkanes/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Benzamides/chemical synthesis , Benzamides/chemistry , Benzamides/pharmacology , Candida albicans/cytology , Cations/chemical synthesis , Cations/chemistry , Cations/pharmacology , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity RelationshipABSTRACT
A novel copper-catalyzed aerobic oxidative C(NOH)-C(alkyl) bond cleavage reaction of aryl/aralkyl/vinyl ketones for the synthesis of aromatic/acrylic acids is described. A series of ketones having aryl/aralkyl/vinyl at the one end and methyl to any higher alkyl at the other end can be selectively cleaved and converted into the corresponding acids via oxime intermediates.
Subject(s)
Acrylates/chemical synthesis , Copper/chemistry , Ketones/chemistry , Oxygen/chemistry , Acrylates/chemistry , Catalysis , Oxidation-ReductionABSTRACT
The present report describes development of a novel, bifunctional molecule possessing both selective antiproliferative activity and siRNA transfection ability. We synthesized a series of cationic lipo-benzamides and screened for in vitro anticancer activities against a panel of cancer and non-cancer cells. The molecule with a ten carbon chain-length (C10M) significantly inhibited proliferation of cancer cells via arresting the cell cycle predominantly in the G1 phase; but did not affect non-cancerous cells. C10M effectively mediated siRNA delivery in vitro. The combined anticancer effect of the delivery of C10M together with its survivin-targeting siRNA cargo was significantly (p < 0.05) superior to that of agent alone. To our knowledge, this is the first report of a dual-purpose molecule with intrinsic anticancer activity and suitability for use in siRNA delivery.