Peptides of natural and synthetic sources are compounds operating in a wide range of biological interactions. They play a key role in biotechnological applications as both therapeutic and diagnostic tools. They are easily synthesized thanks to solid-phase peptide devices where the amino acid sequence can be exactly selected at molecular levels, by tuning the basic units. Recently, peptides achieved resounding success in drug delivery and in nanomedicine smart applications. These applications are the most significant challenge of recent decades: they can selectively deliver drugs to only pathological tissues whilst saving the other districts of the body. This specific feature allows a reduction in the drug side effects and increases the drug efficacy. In this context, peptide-based aggregates present many advantages, including biocompatibility, high drug loading capacities, chemical diversity, specific targeting, and stimuli responsive drug delivery. A dual behavior is observed: on the one hand they can fulfill a structural and bioactive role. In this review, we focus on the design and the characterization of drug delivery systems using peptide-based carriers; moreover, we will also highlight the peptide ability to self-assemble and to actively address nanosystems toward specific targets.

Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors.

Novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC₅₀ in the μM range. In attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward Leishmania donovani were also investigated and revealed their selective antiplasmodial profile. In parallel, the in vitro cytotoxicity of these molecules was assessed on the human HepG2 cell line. Structure–activity relationships of these new synthetic compounds are discussed here. The bis-pyrrolo[1,2-a]quinoxalines 1n and 1p were identified as the most potent antimalarial candidates with selectivity index (SI) of 40.6 on W2 strain, and 39.25 on 3D7 strain, respectively. As the telomeres of the parasite could constitute an attractive target, we investigated the possibility of targeting Plasmodium telomeres by stabilizing the Plasmodium telomeric G-quadruplexes through a FRET melting assay by our new compounds.