[Cu(<i>o</i>‑phthalate)(phenanthroline)] Exhibits Unique Superoxide-Mediated NCI-60 Chemotherapeutic Action through Genomic DNA Damage and Mitochondrial Dysfunction

The <i>in cellulo</i> catalytic production of reactive oxygen species (ROS) by copper­(II) and iron­(II) complexes is now recognized as a major mechanistic model in the design of effective cytotoxins of human cancer. The developmental complex, [Cu­(<i>o</i>-phthalate)­(1,10-phenanthroline)] (<b>Cu-Ph</b>), was recently reported as an intracellular ROS-active cytotoxic agent that induces double strand breaks in the genome of human cancer cells. In this work, we report the broad-spectrum action of <b>Cu-Ph</b> within the National Cancer Institute’s (NCI) Developmental Therapeutics Program (DTP), 60 human cancer cell line screen. The activity profile is compared to established clinical agentsvia the COMPARE algorithmand reveals a novel mode of action to existing metal-based therapeutics. In this study, we identify the mechanistic activity of <b>Cu-Ph</b> through a series of molecular biological studies that are compared directly to the clinical DNA intercalator and topoisomerase II poison doxorubicin. The presence of ROS-specific scavengers was employed for <i>in vitro</i> and intracellular evaluation of prevailing radical species responsible for DNA oxidation with superoxide identified as playing a critical role in this mechanism. The ROS targeting properties of <b>Cu-Ph</b> on mitochondrial membrane potential were investigated, which showed that it had comparable activity to the uncoupling ionophore, carbonyl cyanide <i>m</i>-chlorophenyl hydrazine. The induction and origins of apoptotic activation were probed through detection of Annexin V and the activation of initiator (8,9) and executioner caspases (3/7) and were structurally visualized using confocal microscopy. Results here confirm a unique radical-induced mechanistic profile with intracellular hallmarks of damage to both genomic DNA and mitochondria

Efficient DNA Condensation by a C3?Symmetric Codeine Scaffold

Legacy description not available</p

Synthesis, self-assembly, bacterial and fungal toxicity, and preliminary biodegradation studies of a series of l-phenylalanine-derived surface-active ionic liquids

We report for the first time a comprehensive study on the synthesis (supported by green chemistry metrics), aggregation properties, bacterial/fungal toxicities and preliminary data on biodegradation of a series of 24 L-phenylalanine derived surface-active ionic liquids (SAILs). The various cationic headgroups included pyridinium, imidazolium, and cholinium groups and enabled a comprehensive analysis of the effect of the alkyl ester chain (from C2 to C16) on the synthesis, toxicity, biodegradability, and surfactant properties of the novel SAILs. The evaluation of the SAILs revealed that a wide variety of properties were strictly dependent on the side chain length, including their bacterial and fungal toxicities (from low toxicity to high toxicity), and aggregation properties. Addition of the L-phenylalanine moiety which connects the lipophilic side chain to the cationic head group results in the phenyl group essentially contributing to the self-assembling properties. The interplay of dispersion interactions of the phenyl ring and the side chain hydrophobicity allows us to rank the novel SAILs (thus identifying the remarkable ones) as compared to other surfactants. The CMC values for the SAILs reported in this study are significantly (up to 10 times) lower than those reported for conventional surfactants with the same length of the side chain. Adsorption and micellization are among the factors affecting the toxicity of the studied SAILs. Preliminary biodegradation studies have shown that no clear trend was observed when comparing the closed bottle test results of the SAIL C2 and C10 derivatives. Medium chain length (C6 to C8) pyridinium SAILs have been recommended as the most prospective green alternatives for conventional cationic surfactants. These findings can contribute to designing new efficient amphiphiles with optimized antimicrobial activities and to employ them as potential environmentally benign mineralisable surfactants.</p

C3-symmetric opioid scaffolds are pH-responsive DNA condensation agents

Legacy description not available</p

C3-symmetric opioid scaffolds are pH-responsive DNA condensation agents

Legacy description not available</p

Synthesis, self-assembly, bacterial and fungal toxicity, and preliminary biodegradation studies of a series of l-phenylalanine-derived surface-active ionic liquids

We report for the first time a comprehensive study on the synthesis (supported by green chemistry metrics), aggregation properties, bacterial/fungal toxicities and preliminary data on biodegradation of a series of 24 L-phenylalanine derived surface-active ionic liquids (SAILs). The various cationic headgroups included pyridinium, imidazolium, and cholinium groups and enabled a comprehensive analysis of the effect of the alkyl ester chain (from C2 to C16) on the synthesis, toxicity, biodegradability, and surfactant properties of the novel SAILs. The evaluation of the SAILs revealed that a wide variety of properties were strictly dependent on the side chain length, including their bacterial and fungal toxicities (from low toxicity to high toxicity), and aggregation properties. Addition of the L-phenylalanine moiety which connects the lipophilic side chain to the cationic head group results in the phenyl group essentially contributing to the self-assembling properties. The interplay of dispersion interactions of the phenyl ring and the side chain hydrophobicity allows us to rank the novel SAILs (thus identifying the remarkable ones) as compared to other surfactants. The CMC values for the SAILs reported in this study are significantly (up to 10 times) lower than those reported for conventional surfactants with the same length of the side chain. Adsorption and micellization are among the factors affecting the toxicity of the studied SAILs. Preliminary biodegradation studies have shown that no clear trend was observed when comparing the closed bottle test results of the SAIL C2 and C10 derivatives. Medium chain length (C6 to C8) pyridinium SAILs have been recommended as the most prospective green alternatives for conventional cationic surfactants. These findings can contribute to designing new efficient amphiphiles with optimized antimicrobial activities and to employ them as potential environmentally benign mineralisable surfactants.</p