Trends in Antibiotic-Resistant Bacteria Isolated from Screening Clinical Samples in a Tertiary Care Hospital over the 2018-2022 Period.

To assess the putative impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria recovered from routine screening samples and, more globally, the trends in time to first positive screening sample and carriage duration of those bacteria in patients admitted to a tertiary hospital, data from laboratory results were retrospectively mined over the 2018-2022 period. No significant differences could be found in the number of positive patients or MDR isolates per year, time to positive screening, or carriage duration. Extended-spectrum beta-lactamase producers were dominant throughout the studied period but their relative proportion decreased over time as well as that of meticillin-resistant Staphylococcus aureus. Meanwhile, carbapenemase-producing enterobacteria (CPE) proportion increased. Among the 212 CPE isolates, Klebsiella pneumoniae and Escherichia coli were the more frequent species but, beginning in 2020, a significant rise in Enterobacter cloacae complex and Citrobacter freundii occurred. OXA48 was identified as the leading carbapenemase and, in 2020, a peak in VIM-producing enterobacteria linked to an outbreak of E. cloacae complex during the COVID-19 pandemic was singled out. Finally, a worrisome rise in isolates producing multiple carbapenemases (NDM/VIM and mostly NDM/OXA48) was highlighted, especially in 2022, which could lead to therapeutic dead-ends if their dissemination is not controlled.

Bacillus cereus strains from donor human milk and hospital environment: uncovering a putative common origin using comparative analysis of toxin and infra-red spectroscopy profiles.

Bacillus cereus is reported as a common cause of toxin-induced food poisoning and of contamination in pasteurized human milk donations. As various toxins can be produced by B. cereus, the aim of this work was first to investigate the toxigenic potential and profiles of 63 B. cereus isolates from Amiens Picardie human milk bank. A comparison to the toxigenic profiles of 27 environmental B. cereus isolates harvested in the hospital in which this human milk bank is situated was performed. Toxin gene prevalences were the highest for nhe (ABC) and entFM followed by cytK and hbl(ACD). A 27% prevalence was found for ces human milk isolates, which is higher than previous works reporting on pasteurized milk and dairy products. No significant differences could be found between human milk and environmental isolates regarding toxin gene prevalences and/or toxin gene profiles. The second aim was to establish whether a B. cereus cross-contamination between human milk and the environment could occur. This was achieved with the help of Fourrier-transform infra-red spectroscopy which enabled the discrimination of 2 main clusters of 11 and 8 isolates, each containing human milk and Amiens Picardie human milk bank environmental isolates. For these two clusters, the time sequence showed that human milk isolates were the first to occur and might have contaminated the milk bank environment as well as other human milk donations. Routinely used on B. cereus isolates, Fourrier-transform infra-red spectroscopy could help in rapidly detecting such clusters and in limiting the spread of a B. cereus strain that might generate rejection of pasteurized donation by the human milk bank.

Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-Bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux.

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.

Bacillus cereus contamination of pasteurized human milk donations: frequency, origin, seasonal distribution, molecular typing of strains and proposed corrective/preventive actions.

OBJECTIVES: An increase in pasteurized human milk contamination with Bacillus cereus was witnessed in milk donated to the Amiens-Picardie Human Milk Bank over the 2017-2018 period. To better understand the origin of such an increase, this study aimed to describe the frequency of Bacillus cereus contamination in anonymous and personalized human milk donations of Amiens Human Milk Bank in 2018, compare the genetic profiles of Bacillus cereus strains found in pasteurized human milk and set up corrective/preventive actions to reduce Bacillus cereus contamination. STUDY DESIGN: A retrospective cohort study of human milk donated from January to December 2018 was set. Data on the microbiological quality of donated human milk and genetic profiles of Bacillus cereus strains isolated from pasteurized donated human milk and the environment were collected. RESULTS: The overall noncompliance rate related to the microbiological quality in the 1585 batches of analyzed human milk donations was of 27.3%. Post-Holder pasteurization, rejection rates were significantly higher for anonymous donations as compared to personalized ones. Bacillus cereus was the main cause of noncompliance. Bacillus cereus contaminations could not be attributed to a single strain spreading through Amiens human milk bank and Amiens hospital environment as the genetic profiles of the collected strains were different. Corrective actions led to a decrease in the noncompliance rate due to Bacillus cereus (37.7-9.7%) post-Holder pasteurization. CONCLUSION: Bacillus cereus was the primary cause of rejection for pasteurized human milk donations over the investigated period. These contaminations did not originate from the spread of a single strain. A first round of corrective actions enabled a fair decrease in Bacillus cereus contaminations.

Low-Valent Calix[4]arene Glycoconjugates Based on Hydroxamic Acid Bearing Linkers as Potent Inhibitors in a Model of Ebola Virus Cis-Infection and HCMV-gB-Recombinant Glycoprotein Interaction with MDDC Cells by Blocking DC-SIGN.

In addition to a variety of viral-glycoprotein receptors (e.g., heparan sulfate, Niemann-Pick C1, etc.), dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), from the C-type lectin receptor family, plays one of the most important pathogenic functions for a wide range of viruses (e.g., Ebola, human cytomegalovirus (HCMV), HIV-1, severe acute respiratory syndrome coronavirus 2, etc.) that invade host cells before replication; thus, its inhibition represents a relevant extracellular antiviral therapy. We report two novel p-tBu-calixarene glycoclusters 1 and 2, bearing tetrahydroxamic acid groups, which exhibit micromolar inhibition of soluble DC-SIGN binding and provide nanomolar IC50 inhibition of both DC-SIGN-dependent Jurkat cis-cell infection by viral particle pseudotyped with Ebola virus glycoprotein and the HCMV-gB-recombinant glycoprotein interaction with monocyte-derived dendritic cells expressing DC-SIGN. A unique cooperative involvement of sugar, linker, and calixarene core is likely behind the strong avidity of DC-SIGN for these low-valent systems. We claim herein new promising candidates for the rational development of a large spectrum of antiviral therapeutics.

Efflux Pump Overexpression Profiling in Acinetobacter baumannii and Study of New 1-(1-Naphthylmethyl)-Piperazine Analogs as Potential Efflux Inhibitors.

Overexpression of efflux pumps extruding antibiotics currently used for the treatment of Acinetobacter baumannii infections has been described as an important mechanism causing antibiotic resistance. The first aim of this work was to phenotypically evaluate the overexpression of efflux pumps on a collection of 124 ciprofloxacin-resistant A. baumannii strains. An overexpression of genes encoding one or more efflux pumps was obtained for 19 out of the 34 strains with a positive phenotypic efflux (56%). The most frequent genes overexpressed were those belonging to the RND family, with adeJ being the most prevalent (50%). Interestingly, efflux pump genes coding for MATE and MFS families were also overexpressed quite frequently: abeM (32%) and abaQ (26%). The second aim was to synthesize 1-(1-naphthylmethyl)-piperazine analogs as potential new efflux pump inhibitors and biologically evaluate them against strains with a positive phenotypic efflux. Quinoline and pyridine analogs were found to be more effective than their parent compound, 1-(1-naphthyl methyl)-piperazine. Stereochemistry also played an important part in the inhibitory activity, as quinoline derivative (R)-3a was identified as being the most effective and less cytotoxic. Its inhibitory activity was also correlated with the number of efflux pumps expressed by a strain. The results obtained in this work suggest that quinoline analogs of 1-(1-naphthylmethyl)-piperazine are promising leads in the development of new anti-Acinetobacter baumannii therapeutic alternatives in combination with antibiotics for which an efflux-mediated resistance is suspected.

Brass Alloys: Copper-Bottomed Solutions against Hospital-Acquired Infections?

Copper has been used for its antimicrobial properties since Antiquity. Nowadays, touch surfaces made of copper-based alloys such as brasses are used in healthcare settings in an attempt to reduce the bioburden and limit environmental transmission of nosocomial pathogens. After a brief history of brass uses, the various mechanisms that are thought to be at the basis of brass antimicrobial action will be described. Evidence shows that direct contact with the surface as well as cupric and cuprous ions arising from brass surfaces are instrumental in the antimicrobial effectiveness. These copper ions can lead to oxidative stress, membrane alterations, protein malfunctions, and/or DNA damages. Laboratory studies back up a broad spectrum of activity of brass surfaces on bacteria with the possible exception of bacteria in their sporulated form. Various parameters influencing the antimicrobial activity such as relative humidity, temperature, wet/dry inoculation or wear have been identified, making it mandatory to standardize antibacterial testing. Field trials using brass and copper surfaces consistently report reductions in the bacterial bioburden but, evidence is still sparse as to a significant impact on hospital acquired infections. Further work is also needed to assess the long-term effects of chemical/physical wear on their antimicrobial effectiveness.

Validation of a Worst-Case Scenario Method Adapted to the Healthcare Environment for Testing the Antibacterial Effect of Brass Surfaces and Implementation on Hospital Antibiotic-Resistant Strains.

The evaluation of antibacterial activity of metal surfaces can be carried out using various published guidelines which do not always agree with each other on technical conditions and result interpretation. Moreover, these technical conditions are sometimes remote from real-life ones, especially those found in health-care facilities, and do not include a variety of antibiotic-resistant strains. A worst-case scenario protocol adapted from published guidelines was validated on two reference strains (Staphylococcus aureus ATCC 6538 and Enterobacter aerogenes ATCC 13048). This protocol was designed to be as close as possible to a healthcare facility environment, including a much shorter exposure-time than the one recommended in guidelines, and evaluated the impact of parameters such as the method used to prepare inocula, seed on the surface, and recover bacteria following exposure. It was applied to a panel of 12 antibiotic-resistant strains (methicillin resistant, vancomycin-resistant, beta-lactamase, and carbapenemase producing strains as well as efflux pump-overexpressing ones) chosen as representative of the main bacteria causing hospital acquired infections. Within a 5-min exposure time, the tested brass surface displayed an antibacterial effect meeting a reduction cut-off of 99% compared to stainless steel, whatever the resistance mechanism harbored by the bacteria.

Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives.

A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.

Bacterial ecology and antibiotic resistance mechanisms of isolated resistant strains from diabetic foot infections in the north west of Algeria.

BACKGROUND: In front of the polymorphic bacterial ecology and antibiotic resistance in diabetic patients with foot infections and good patient care, collaboration between clinicians and microbiologists is needed to improve assessment and management of patients with this pathology. OBJECTIVE: This study was designed to characterize the bacterial ecology of diabetic foot infection (DFIs) and to determine the different mechanisms of resistance involved. METHODS: In this study bacterial strains and antibiotic resistance profiles were determined from diabetic foot infections patients (n = 117). The identification of resistance mechanisms, such as penicillinase and/or extended-spectrum ß-lactamase production (ESBL), methicillin-resistant Staphylococcus aureus (MRSA) and efflux pump over-expression were performed. RESULTS: A high prevalence of Gram-negative bacteria (61%) with Escherichia coli, and other Enterobacteriaceae and Pseudomonas aeruginosa being the predominant isolates. Gram positive bacteria mainly represented by Staphylococcus aureus accounted for 39% of the isolates. 93.5% of the Enterobacteriaceae were resistant to, at least, one molecule in the ß-lactam family, while the majority of the Staphylococci were resistant to penicillin G and tetracycline (93.3% and 71.7%). The majority of non-fermenting Gram negative bacteria were also resistant to fluoroquinolones. ß-lactamase detection tests revealed the presence of extended-spectrum ß-lactamase in 43.5% of the Enterobacteriaceae, while methicillin-resistant Staphylococcus aureus represented 18.2% of the isolates. Additionally, 50.9% of non-fermenting Gram negative bacteria were overproducing efflux pumps. CONCLUSION: All Acinetobacter Baumannii were Multidrug-Resistant (MDR), as the majority of Staphylococci, and Enterobacteriaceae. These results should be taken into account by the clinician in the prescription of probabilistic antibiotic therapy in this context.

Study of Iron Piperazine-Based Chelators as Potential Siderophore Mimetics.

Gram-negative bacteria's resistance such as Pseudomonas aeruginosa and the Burkholderia group to conventional antibiotics leads to therapeutic failure. Use of siderophores as Trojan horses to internalize antibacterial agents or toxic metals within bacteria is a promising strategy to overcome resistance phenomenon. To combat the Pseudomonas sp, we have synthesized and studied two piperazine-based siderophore mimetics carrying either catecholate moieties (1) or hydroxypyridinone groups (2) as iron chelators. These siderophore-like molecules were prepared in no more than four steps with good global yields. The physicochemical study has highlighted a strong iron affinity since their pFe values were higher than 20. 1 possesses even a pFe value superior than those of pyoverdine, the P. aeruginosa endogenous siderophore, suggesting its potential ability to compete with it. At physiological pH, 1 forms mainly a 2:3 complex with iron, whereas two species are observed for 2. Unfortunately, the corresponding Ga(III)-1 and 2 complexes showed no antibacterial activity against P. aeruginosa DSM 1117 strain. The evaluation of their siderophore-like activity showed that 1 and 2 could be internalized by the bacteria.

Glycocluster Tetrahydroxamic Acids Exhibiting Unprecedented Inhibition of Pseudomonas aeruginosa Biofilms.

Opportunistic Gram-negative Pseudomonas aeruginosa uses adhesins (e.g., LecA and LecB lectins, type VI pili and flagella) and iron to invade host cells with the formation of a biofilm, a thick barrier that protects bacteria from drugs and host immune system. Hindering iron uptake and disrupting adhesins' function could be a relevant antipseudomonal strategy. To test this hypothesis, we designed an iron-chelating glycocluster incorporating a tetrahydroxamic acid and α-l-fucose bearing linker to interfere with both iron uptake and the glycan recognition process involving the LecB lectin. Iron depletion led to increased production of the siderophore pyoverdine by P. aeruginosa to counteract the loss of iron uptake, and strong biofilm inhibition was observed not only with the α-l-fucocluster (72%), but also with its α-d-manno (84%), and α-d-gluco (92%) counterparts used as negative controls. This unprecedented finding suggests that both LecB and biofilm inhibition are closely related to the presence of hydroxamic acid groups.

Synthesis and Study of New Quinolineaminoethanols as Anti-Bacterial Drugs.

The lack of antibiotics with a novel mode of action associated with the spread of drug resistant bacteria make the fight against infectious diseases particularly challenging. A quinoline core is found in several anti-infectious drugs, such as mefloquine and bedaquiline. Two main objectives were set in this work. Firstly, we evaluated the anti-mycobacterial properties of the previous quinolines 3, which have been identified as good candidates against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli) bacteria. Secondly, a new series 4 was designed and assessed against the same bacteria strains, taking the pair of enantiomers 3m/3n as the lead. More than twenty compounds 4 were prepared through a five-step asymmetric synthesis with good enantiomeric excesses (>90%). Interestingly, all compounds of series 3 were efficient on M. avium with MIC = 2-16 µg/mL, while series 4 was less active. Both series 3 and 4 were generally more active than mefloquine against the ESKAPEE bacteria. The quinolines 4 were either active against Gram-positive bacteria (MIC ≤ 4 µg/mL for 4c-4h and 4k/4l) or E. coli (MIC = 32-64 µg/mL for 4q-4v) according to the global lipophilicity of these compounds.

MexXY Multidrug Efflux System Is More Frequently Overexpressed in Ciprofloxacin Resistant French Clinical Isolates Compared to Hospital Environment Ones.

Modulation of the membrane permeability through a decrease in porin-mediated antibiotic entry and/or an increase in antibiotic efflux is one of the resistance mechanisms to antibiotics evolved by Gram-negative bacteria. To assess whether the outer membrane porin OprD and Resistance-Nodulation-Division (RND) efflux pumps were similarly expressed in 33 ciprofloxacin-resistant clinical strains of Pseudomonas aeruginosa and in 30 non-clinical strains originating from the hospital environment (mainly waterborne Pseudomonas aeruginosa), the expression of oprD, mexB, mexF, and mexY genes was investigated. Overall, the expression of oprD was not detected by RT-qPCR in 14 (22%) strains and underexpressed in 35 (56%) more. No significant difference in oprD expression was detected between clinical and non-clinical strains. As for efflux pumps, 23 (70%) of the clinical strains overexpressed at least one of the tested RND genes. Overexpression of mexB, mexF and mexY was detected in 27, 12, and 45% of the clinical strains, respectively. In the 30 non-clinical strains, no overexpression could be found for mexB, mexF, or mexY. On the contrary, a global underexpression of the tested efflux pump genes was recorded. In both clinical and environmental strains, a positive correlation was found between the expressions of oprD and mexB. Similarly, the expressions of oprD and mexF were positively correlated. This result contrasts with the inverse correlation between both MexAB-OprM/MexEF-OprN and OprD previously described in carbapenem-resistant P. aeruginosa strains. The only positive correlation between phenotypic ciprofloxacin minimum inhibitory concentrations (MICs) and the expression of efflux pump gene was witnessed with mexY (analysis on pooled results for clinical and environmental strains). However, in clinical strains, no statistically significant link could be found between the degree of reduction in ciprofloxacin MICs witnessed with Phenylalanine-Arginine ß-naphthylamide (PAßN) and the expression of any of the 3 RND genes tested.

Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[ 1,2-a]quinoxalines.

BACKGROUND: We prepared a novel series of enantiopure mefloquine analogues with pyrrolo[ 1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant strain. OBJECTIVES: To observe the influence of pyrrolo[1,2-a]quinoxaline core versus quinoline core on the antimalarial activity. METHOD: Four enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless asymmetric dihydroxylation reaction in eight steps. Their antimalarial activity was evaluated on two Plasmodium falciparum strains 3D7 and W2 with a SYBR Green I fluorescence-based method and their cytotoxicity was measured on four cell lines HepG2, THP-1, CHO and HFF. RESULTS: IC50 values of the four compounds 2 were close to the micromolar against the two P. falciparum strains. They were more active against P. falciparum strain W2 vs. P. falciparum strain 3D7. (R)- enantiomers were always more active than their (S)-counterpart whatever the strain. Selectivity indexes of compounds 2 were lower than 100. CONCLUSION: A novel series of enantiopure aminoalcohols with pyrrolo[1,2-a]quinoxaline core were synthesized in eight steps. They displayed IC50 values close to the micromolar against two P. falciparum strains 3D7 and W2. Although, In this series, 2,8-bistrifluoromethylquinoline was a best core than pyrrolo[1,2-a]quinoxaline for an optimal antimalarial activity, the pyrroloquinoxaline 2b showed an interesting antimalarial activity.

Design, synthesis, and antiprotozoal evaluation of new 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives.

A series of new 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives was synthesized, and the compounds were 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. The in vitro cytotoxicity of these molecules was assessed by incubation with human HepG2 cells; for some derivatives, cytotoxicity was observed at significantly higher concentrations than antiparasitic activity. The 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline 1h was identified as the most potent antimalarial candidate with ratios of cytotoxic-to-antiparasitic activities of 107 and 39 against a chloroquine-sensitive and a chloroquine-resistant strain of P. falciparum, respectively. As the telomeres of the parasite P. falciparum are the likely target of this compound, we investigated stabilization of the Plasmodium telomeric G-quadruplexes by our phenanthroline derivatives through a FRET melting assay. The ligands 1f and 1m were noticed to be more specific for FPf8T with higher stabilization for FPf8T than for the human F21T sequence.

Synthesis, iron(III) complexation properties, molecular dynamics simulations and P. aeruginosa siderophore-like activity of two pyoverdine analogs.

P. aeruginosa ranks among the top five organisms causing nosocomial infections. Among the many novel strategies for developing new therapeutics against infection, targeting iron uptake mechanism seems promising as P. aeruginosa needs iron for its growth and survival. To scavenge iron, the bacterium produces siderophores possessing a very high affinity towards Fe(III) ions such as pyoverdines. In this work, we decided to study two pyoverdine analogs, aPvd2 and aPvd3, structurally close to the endogen pyoverdine. The pFe constants calculated with the values of formation showed a high affinity of aPvd3 towards Fe(III). Molecular dynamics calculations demonstrated that aPvd3-Fe forms with Fe(III) stable 1:1 complexes in water, whereas aPvd2 does not. Only aPvd3 is able to increase the bacterial growth and represents thus an alternative to pyoverdine for iron acquisition by the bacterium. The aPvd2-3 interaction studies with a lipid membrane indicated that they were unable to interact and to cross the plasma membrane of bacteria by passive diffusion. Consequently, the penetration of aPvd3 is ruled by a transport membrane protein. These results showed that aPvd3 may be used to inhibit pyoverdine uptake or to promote the accumulation and release of antibiotics into the cell following a Trojan horse strategy.

Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives.

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.