G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents. Small organic heterocyclic molecules are well known to target and stabilize G4 structures. In this article, we have designed and synthesized 2,6-di-(4-carbamoyl-2-quinolyl)pyridine derivatives and their ability to stabilize G4-structures have been determined through the FRET melting assay. It has been established that these ligands are selective for G4 over duplexes and show a preference for the parallel conformation. Next, telomerase inhibition ability has been assessed using three cell lines (K562, MyLa and MV-4-11) and telomerase activity is no longer detected at 0.1 μM concentration for the most potent ligand 1c. The most promising G4 ligands were also tested for antiproliferative activity against the two human myeloid leukaemia cell lines, HL60 and K562.

A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC₅₀ values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC₅₀ from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.

1-Phenyl-8-[[4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]methyl]-1,3,8-triazaspiro[4.5]decan-4-one has been successfully synthesized via a multi-step pathway starting from 2-nitroaniline. Structure characterization of this original pyrrolo[1,2-a]quinoxaline derivative was achieved by FT-IR, ¹H-NMR, ¹³C-NMR, X-Ray and HRMS spectral analysis. This title compound shows interesting cytotoxic potential against several human leukemia cell lines (K562, HL60, and U937 cells).

1,3-Dihydro-1-{1-[4-(4-phenylpyrrolo[1,2-a]quinoxalin-3-yl)benzyl]piperidin-4-yl}-2H-benzimidazol-2-one has been synthesized through a multi-step pathway starting from commercially available 2-nitroaniline. A structure characterization of this new substituted pyrrolo[1,2-a]quinoxaline compound was achieved by using FT-IR, ¹H-NMR, ¹³C-NMR, X-Ray and HRMS spectral analysis. This new pyrroloquinoxaline derivative shows an interesting cytotoxic potential against several human leukemia cell lines (HL60, K562 and U937 cells).

A series of new 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated in vitro against two parasites (Plasmodium falciparum and Leishmania donovani). The biological results showed antimalarial activity with IC₅₀ values in the sub and μM range. The in vitro cytotoxicity of these new aza polyaromatic derivatives was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene 1m was found as one of the most potent and promising antimalarial candidates with a ratio of cytotoxic to antiprotozoal activities of 83.67 against the P. falciparum CQ-sensitive strain 3D7. In addition, derivative 1r was also identified as the most interesting antimalarial compound with a selectivity index (SI) of 17.28 on the W2 P. falciparum CQ-resistant strain. It was previously described that the telomeres of P. falciparum could be considered as potential targets of these kinds of aza heterocycles; thus, the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes was measured through a FRET melting assay.

1H-3-{4-[(3-Dimethylaminopropyl)aminomethyl]phenyl}-2-phenylindole was synthesized via a multi-step pathway starting from 2-iodoaniline. Structure characterization of this new indole compound was achieved by ¹H-NMR, ¹³C-NMR and ESI-MS spectral analysis. The title compound was screened in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Biological results showed antiparasitic activity with IC₅₀ values in the μM range.