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Leishmaniasis constitutes a severe public health problem, with an estimated prevalence of 12 million cases. This potentially fatal disease has a worldwide distribution and in 2012, the fatal Visceral Leishmaniasis (VL) was declared as new emerging disease in Europe, mainly due to global warming, with expected important public health impact. The available treatments are toxic, costly or lead to parasite resistance, thus there is an urgent need for new drugs with new mechanism of action. Previously, we reported the discovery of CTN1122, a potent imidazo[1,2-a]pyrazine-based antileishmanial hit compound targeting L-CK1.2 at low micromolar ranges. Here, we described structurally related, safe and selective compounds endowed with antiparasitic properties, better than miltefosine, the reference therapy by oral route. L-CK1.2 homology model gave the first structural explanations of the role of 4-pyridyl (CTN1122) and 2-aminopyrimidin-4-yl (compound 21) moieties, at the position 3 of the central core, in the low micromolar to nanomolar L-CK1.2 inhibition, whereas N-methylpyrazole derivative 11 remained inactive against the parasite kinase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

A series of (imidazo[1,2-a]pyrazin-6-yl)ureas were synthesized through 6-aminoimidazo[1,2-a]pyrazine as a key intermediate. 1-(Imidazo[1,2-a]pyrazin-6-yl)-3-(4-methoxy - phenyl)urea displayed a cytostatic activity against a non-small cell lung cancer cell line and was chosen for further mechanistic studies. Growth kinetics highlighted a selective dose-dependent response of P53-mutant NSCLC-N6-L16 cell line and overexpression of TP53 gene induced by this compound. These pharmacological data suggest a promising reactivation of p53 mutant in NSCLC-N6-L16 cell line., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity against the promastigote and the amastigote forms of Leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3T3 mouse fibroblast cells. Through LmCK1 inhibition assay, investigations of the putative molecular target of these promising antileishmanial compounds will be discussed., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Two 3-(alpha-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L. mexicana axenic amastigotes, were 4.4 +/- 0.1 and 6.4 +/- 0.1 microM, respectively. Against intracellular amastigotes, PM17 produced a 66% decrease of leishmanial burden at 1 microM and PM19 had an IC50 of 1.3 microM. In a Balb/c mice model of L. major leishmaniasis, administration of PM17 led to a clear-cut parasite burden reduction: 98.9% in the spleen, 79.0% in the liver and 49.9% in the popliteal node draining the cutaneous lesion. As anticipated, it was brought to the fore that PM17 decreases ergosterol biosynthesis leading to membrane fungal cell alterations. Moreover it was proved that this imidazole antifungal agent induces a parasite burden-correlated decrease in interleukine-4 production both in the splenocyte and the popliteal node of the mouse.

Quorum sensing, an important process of bacterial communication, is involved in the development of complex behavior and expression of virulence factors that become important due to its key role in infection process. In this manuscript, docking studies were used as a preliminary screening to identify main interactions between LuxR receptor (CviR) of Chromobacterium violaceum as model and N‐acyl L‐homoserine lactones. Thus, following this approach, a library of imidazo[1,2‐a]pyridines bearing carboxamide and urea moieties was designed, evaluated on this in silico model previously validated, and synthesized to generate new potential quorum sensing inhibitors. The present article summarizes survey to develop these new molecules with potential biological activity, based on interaction analysis ligand‐receptor. [ABSTRACT FROM AUTHOR]

This present study identifies a number of azolyl-substituted indoles as potent inhibitors of aromatase. In the sub-series of 3-(azolylmethyl)-1H-indoles, four imidazole derivatives and their triazole analogues were tested. Imidazole derivatives 11 and 14 in which the benzyl moiety was substituted by 2-chloro and 4-cyano groups, respectively, were the most active, with IC50 values ranging between 0.054 and 0.050 μM. In the other sub-series, eight 3-(α-azolylbenzyl)-1H-indoles were prepared and tested. Compound 30, the N-ethyl imidazole derivative, proved to be an aromatase inhibitor, showing an IC50 value of 0.052 μM. All target compounds were further evaluated against 17α-hydroxylase/C17,20-lyase to determine their selectivity profile. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Exploration of Versatile Reactions on 2-Chloro-3-nitroimidazo[1,2-a]pyridine: Expanding Structural Diversity of C2- and C3-Functionalized Imidazo[1,2-a]pyridines" by A. Tonnerre et al. published in the "Tetrahedron Letters" in 2013.