Structure-activity relationships of novel substituted naphthalene diimides as anticancer agents

Novel 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity on a wide number of different tumor cell lines. The prototypes of the present series were derivatives 1 and 2 characterized by interesting biological profiles as anticancer agents. The present investigation expands on the study of structure-activity relationships of prototypes 1 and 2, namely, the influence of the different substituents of the phenyl rings on the biological activity. Derivatives 3-22, characterized by a different substituent on the aromatic rings and/or a different chain length varying from two to three carbon units, were synthesized and evaluated for their cytostatic and cytotoxic activities. The most interesting compound was 20, characterized by a linker of three methylene units and a 2,3,4-trimethoxy substituent on the two aromatic rings. It displayed antiproliferative activity in the submicromolar range, especially against some different cell lines, the ability to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Its theoretical recognition against duplex and quadruplex DNA structures have been compared to experimental thermodynamic measurements and by molecular modeling investigation leading to putative binding modes. Taken together these findings contribute to define this compound as potential Multitarget-Directed Ligands interacting simultaneously with different biological targets. \ua9 2012 Elsevier Masson SAS. All rights reserved

Risultati prova di esame di laboratorio del Corso di Aanalisi dei prodotti per la salute 1, Turno B

La presenza del nome chimico nella tabella indica l'erroneo riconoscimento della sostanz

Risultati prova finale Analisi farmaceutica 1 modulo analisi qualitativa

Per qualsiasi chiarimento e delucidazione mi potete contattare per richiedere un appuntamento a [email protected]

Introduzione 1-3

Materiale per uso personal

Dispense di laboratorio 1 Modulo

E' necessario avere una copia delle dispense da utilizzare durante le esercitazion

A rational design of new multi-target-directed-ligands for the treatment of Alzheimer's disease

Alzheimer’s disease (AD) is a multifactorial disease and an age-related neurodegenerative disorder clinically characterized by loss of memory and progressive deficits in different cognitive domains. Much effort has been devoted to elucidate the relationships between the hallmarks of the disease, that is, i) amyloid-β (Aβ) plaques, a massive deposit of amyloid peptide generated by successive cleavage of the amyloid precursor protein (APP) by β-(BACE-1) and γ-secretase, ii) neurofibrillary tangles (NFT), and iii) loss of neurons in the hippocampus and nucleus basalis of Maynart. AD is characterized by a pronounced degradation of the cholinergic system and by alteration in other neurotransmitter systems such as the glutamatergic and serotoninergic ones. Despite considerable scientific progress, the aetiology of AD is still unknown and speculated about. The current pharmacological approach is mainly based on the so-called “cholinergic hypothesis”, which states that restoration of the cholinergic functionalities can be achieved by cholinomimetic agents acting at the synaptic level. A more recent strategy, proposes that it is possible the design and synthesis of multi-target-directed-ligands (MTDL), single molecules able to hit several targets responsible for the multifaceted aetiology of AD.1 Following this strategy, our group has been involved for a long time in the design and synthesis of compounds for AD treatment. The prototype of such derivatives was caproctamine (1).2 SAR studies carried out on 1 structure allowed us to provide derivatives endowed with multipotent biological profile.3-5 By exploiting “the frozen analogue approach” we subsequently designed and synthesized new MTDL’s derived from 1 and able to hit several peculiar targets involved in AD pathogenesis. The results of this research will be illustrated