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Gastrointestinal strongylosis, which causes deadly seasonal diarrhea in small ruminants, is a major threat to the livestock population in sub-Saharan Africa. Moreover, livestock is a central component of food security. In addition to this threat, there is a poor veterinary coverage due to the increasing lack of effective anthelmintic drugs against strongyles because of the emergence and proliferation of chemo resistant strains. In this context, and given that the use of a vaccine is not widespread, the establishment of the therapeutic arsenal available to veterinarians to control strongyles will contribute to the food and economic security of rural populations. This review outlines the main pharmacochemical classes of anthelmintics used in the management of strongylosis of small ruminants.

Introduction: Present leishmaniasis treatment regimen has many limitations including severe adverse effects, toxicity, and Leishmania strains resistance. In the present study, the objective is to perform QSAR, molecular docking and ADME prediction studies on benzimidazolylchalcones in order to select an antileishmanial drug candidate.Materials & methods: QSAR models were performed on 12 benzimidazolylchalcones with antileishmanial activities against promastigote strains of L. donovani. Binding free energy calculations were performed using MM-GBSA to assess the affinity of the ligands for the proteins. In addition, the three most active compounds (4a-c, IC50

Background: To overcome drug resistance to current antimalarial drugs, we propose the synthesis and in vitro evaluation of the antiplasmodial activity of a series of 5-chlorobenzimidazolyl-chalcones against chloroquino sensitive (CQ-S) and chloroquino resistant (CQ-R) strains of P. falciparum. Objective: This study aimed to establish through structure-activity relationship studies and docking, the structural elements essential for antiplasmodial activities. Methods: The antiplasmodial activity of these benzimidazolylchalcones was carried out according to the Rieckmann microtest technique, followed by the determination of the concentrations inhibiting 50% of the production of parasitic HRP2 antigens (IC50) by ELISA. Chloroquine was used as a reference molecule with a sensitivity threshold set at 100 µM. Molecular docking was performed using sensitive (PDB ID: 1J3I) and resistant (PDB ID: 4DP3) dihydrofolate reductase-thymidylate synthase proteins (PfDHFR-TS). Results: All benzimidazolylchalcones tested expressed antiplasmodial activities especially against chloroquine resistant isolates (IC50 = 0.32-44.38 µM). The best profile against both isolates was the methoxylated derivative (3e) with an IC50 ranging from 0.32 to 1.96 µM. This compound had the best antimalarial activity against CQ-S isolates. On CQ-R isolates, the unsubstituted 5-chlorobenzimidazole derivative (3b) had exalted activity (IC50 = 0.78 µM). We selected a weakly active non-chlorinated derivative 3a and chlorinated derivatives 3b, 3d, 3e and 3f) with IC50< 3µM against the chloroquine-resistant strain to perform docking studies. These revealed that the pyrrolic nitrogen of benzimidazole and the ketone of propenone are the main chemical entities involved in the interaction at the receptor. Moreover, ADMET studies showed favorable pharmacokinetic properties. Conclusion: Molecular docking studies confirmed the experimental findings and revealed the possible interactions pattern. Derivatives 3b and 3e, which showed promising binding affinities against PfDHFR-TS, can be proposed as lead compounds for the development of antimalarial drug candidates.

Antifungal therapeutics is confronted today with the challenge of drug resistance of most fungal germs to current antifungal drugs. Faced with this situation, the search for new and more efficient antifungal molecules that avoid the phenomenon of drug resistance becomes an urgent task. The design of new antifungal drugs acting on new biological targets and/or by innovative mechanisms of action is essential in the fight against fungal infections. Current advances in molecular biology have identified new targets for the development of new antifungal therapy. Several biological targets for the development of new antifungal agents are currently being explored. Amongst these, the most promising are BET (Bromodomain and Extra-Terminal) proteins, Homoserine transacetylase (HTA), mannan cell wall, Glycosylphosphatidylinositols (GPI) anchor biosynthesis, Histone deacetylases, Sphingolipid biosynthesis, D9 fatty acid desaturase and Chitin biosynthesis. This review summarizes the new biological targets and their inhibitors under development as potential new antifungal drugs.

This QSAR study involved a series of benzimidazolylchalcone derivatives. It allowed us to obtain a model from the molecular descriptors and anthelminthical activity against Haemonchus contortus. The molecular descriptors were obtained by applying the methods of quantum chemistry at the B3LYP/6-31G (d) level. The statistical indicators of the model are: the coefficient of determination R2 equals 0.990, the standard deviation S equals 0.209, the Fischer coefficient F equals 153.055 and the cross-validation coefficient equals 0.990. This model has good statistical performances. The quantum descriptors of dipole moment (μD) and electronic energy are responsible of the anthelminthic activity of benzimidazolylchalcone derivatives. In addition, the dipole moment is the priority descriptor for the prediction of the antibacterial activity of the studied compounds. The Eriksson et al. acceptance criteria used for the test set is verified. The values of the pCL100theo/pCL100exp ratio of the theoretical and experimental activities for the test set aim towards the unit.

Malaria continues to kill thousands of people worldwide. People South of the Sahara are paying the heaviest price for this epidemic. In addition, the resistance of Plasmodium falciparum which spreads to artemisinin derivatives becomes worrying. To respond to this emergency, the search for new molecules effective against the parasite is essential. Otherwise, chalcones have shown their potential as an effective pharmaceutical agent in numerous studies. However, despite their mainly antiparasitic efficacy, several compounds have been shown to be cytotoxic. This study aimed to assess the cytotoxic profile of chalcone derivatives. Cytotoxicity tests were carried out according to the method described by Taylor and collaborators on Vero cells. The 96-well plates were used in carrying out this study, 100 µl of the compounds were added with concentrations ranging from 7.5 to 1000 µg/ml in DMEM. The results obtained report three compounds derivatives (Chal_B14, Chal_B17 & Chal_SCA03) no-cytotoxic with LDH product values between 129 - 132.5 U/L and ATP ranging from 8.55 to 13.6 RLU. The IC50s for no-cytotoxic compounds ranged from 102 to 236 µM. On the other hand, the cytotoxic compounds had IC50s of less than 30 µM. The results of this study show that the derivatives Chal_B14, Chal_B17 & Chal_SCA03 are candidate compounds with a view to finding new molecules.

The management of candidiasis, once effective, is becoming more and more difficult with the increase of resistance of various Candida species to classical antifungals. It is in this context that we reported in our previous works the pharmacochemical development of new diazaheteroaryls derivatives functionalized with a Michael acceptor such as arylpropenone, arylacrylonitrile and arylcyanopropenone. These diazaheteroaryls derivatives with benzimidazolyl-arylpropenone or benzimidazolyl-arylacrylonitriles or benzimidazolyl-arylcyanopropenone and imidazopyridinyl-arylpropenones structure were obtained by chemical synthesis and then characterized by the usual spectroscopic methods (NMR and MS). The anticandidosic activities of these derivatives expressed as Minimum Inhibitory Quantity (MIQ) were determined in vitro on a clinical strain of Candida albicans, following the bioautography technique. The results show that diazaheteroaryls functionalized by a Michael acceptor have remarkable activities with IMQ ranging from 10 to 0.16 µg. Moreover, the anticandidosic performance of the different derivatives were related to the nature of the Michael acceptor and the structural variations undertaken on the benzene homocycle. This paper, which is the synthesis of a decade of research by our team, will address the pharmacochemical design, chemical synthesis and overall serial structure-anticandidosic activity studies of diaza-heteroaryls functionalized with a Michael acceptor in order to propose compounds that can be developed as anticandidosic drug candidates.

The synthesis of a hybrid mol­ecule is reported. The crystal structure of the monohydrate was investigated using Hirshfeld surface analysis and enrichment contact ratios. Hydrogen bonds induced by guest water mol­ecules are the main driving force in crystal packing formation., In the title hydrated hybrid compound C14H14N2OS2·H2O, the planar imidazo[1,2-a]pyridine ring system is linked to the 1,3-di­thiol­ane moiety by an enone bridge. The atoms of the C—C bond in the 1,3-di­thiol­ane ring are disordered over two positions with occupancies of 0.579 (14) and 0.421 (14) and both disordered rings adopt a half-chair conformation. The oxygen atom of the enone bridge is involved in a weak intra­molecular C—H⋯O hydrogen bond, which generates an S(6) graph-set motif. In the crystal, the hybrid mol­ecules are associated in R 2 2(14) dimeric units by weak C—H⋯O inter­actions. O—H⋯O hydrogen bonds link the water mol­ecules, forming infinite self-assembled chains along the b-axis direction to which the dimers are connected via O—H⋯N hydrogen bonding. Analysis of inter­molecular contacts using Hirshfeld surface analysis and contact enrichment ratio descriptors indicate that hydrogen bonds induced by water mol­ecules are the main driving force in the crystal packing formation.

The extension of Plasmodium falciparum resistance to existing antimalarial drugs is worrying. Faced with this problem, the search for new and effective molecules is necessary. In this context, six chalcone derivatives (B1, B11, B14, B17, SCA02 and SCA03) were tested on field isolates and then reference strains to evaluate their antiplasmodial activity by using the Rieckmann semi-microtest, recommended by WHO, for in vitro and ex vivo activity tests. Compounds B14 and B17 exhibited promising antiplasmodial activities (IC50s: 14.41-16.40 μM) regardless of the type of isolate. Compounds B1, B11, SCA02 and SCA03 showed a moderate inhibition of field isolates (IC50S: 25.63-48.29 μM) and very good activity against reference strains (IC50s: 3.82-10.03 μM). Therefore, more structural modulations should improve their efficiency and make these molecules very good candidates for future effective antimalarial drugs.

International audience; Several phenanthrolinic analogs of quinolones have been synthesized and their antibacterial activity tested against Mycobacterium tuberculosis, other mycobacterial species and bacteria from other genera. Some of them show high activity (of the range observed for rifampicin) against M. tuberculosis replicating in vitro and in vivo (infected macrophages) conditions. These derivatives show the same activity with all or several M. tuberculosis complex bacterial mutants resistant to fluoroquinolones (FQ). This opens the way to the construction of new drugs for the treatment of FQ resistant bacterial infections, including tuberculosis. Several compounds showed also activity against Staphylococcus aureus and probably other species. These compounds do not show major toxicity. We conclude that the novel phenanthrolinic derivatives described here are potent hits for further developments of new antibiotics against bacterial infectious diseases including tuberculosis in particular those resistant to FQ.

The extension of Plasmodium falciparum resistance to existing antimalarial drugs is worrying. Faced with this problem, the search for new and effective molecules is necessary. In this context, six chalcone derivatives (B1, B11, B14, B17, SCA02 and SCA03) were tested on field isolates and then reference strains to evaluate their antiplasmodial activity by using the Rieckmann semi-microtest, recommended by WHO, for in vitro and ex vivo activity tests. Compounds B14 and B17 exhibited promising antiplasmodial activities (IC(50s): 14.41–16.40 μM) regardless of the type of isolate. Compounds B1, B11, SCA02 and SCA03 showed a moderate inhibition of field isolates (IC(50S): 25.63–48.29 μM) and very good activity against reference strains (IC50s: 3.82–10.03 μM). Therefore, more structural modulations should improve their efficiency and make these molecules very good candidates for future effective antimalarial drugs.

Resume Le present travail decrit la conception, par juxtaposition d’entites anti-infectieuses, d’une serie de composes hybrides a structure imidazopyridinyl-arylpropenone. Ces composes ( 5a–y) ont ete synthetises par crotonisation entre la 1-(2-methylimidazo[1,2- a ]pyridin-3-yl)ethanone ( 3 ) et divers benzaldehydes ( 4 ). Leurs structures ont ete determinees par spectrometrie de masse RMN et ESI. Le criblage de ces composes vis-a-vis d’agents pathogenes parasitaires et microbiens montre que le compose 5q (CI 50 = 1,52 μM) pourrait etre retenu pour un developpement contre le paludisme a Plasmodium falciparum chloroquino-resistant. Contre les helminthoses veterinaires a Haemonchus contortus , trois composes s’averent d'interet : il s’agit des composes 5n, 5s et 5w (CL 100 = 7,1–1,5 nM). Contre les candidoses a Candida albicans pharmacoresistants, trois autres composes meritent d’etre retenus : les composes 5e, 5g et 5v (QMI = 1,25–0,31 μg). Cette etude montre que l’enchainement fonctionnel arylpropenone vectorise par l’imidazopyridine peut etre considere comme un nouveau pharmacophore d’activites anti-infectieuses potentielles.

We report the synthesis of a series of imidazo[1,2- a ]pyridine-based molecules as anthelmintic against the livestock parasite Haemonchus contortus . The molecules were tested by using Larval Paralysis Test (LPT), in order to target ionic channels, as most of the prominent marketed anthelminthics present such mechanism of action. The most active compound ( 5e ) displayed paralysis on H. contortus stage 3 larvae until 31.25 µM. Effect of 5e on H. contortus cholinergic receptors (L-AChR1 and 2) was characterized via electrophysiological measurement and a rare antagonist mode of action was unveiled.

The aim of this study is to find potent biomolecules against infectious germs. Based on the reactivity of some key positions of the benzimidazole core, the first part of this work consisted of the synthesis of a series of substituted 2-thioalkylaryl-benzimidazoles 3a-d. Then, another series of N -alkyl-2-thioalkylarylbenzimidazoles 5a-d, 7a-c and 9b-c was also prepared from 2-thioalkylaryl-benzimidazoles by substitution on position-1 of benzimidazole core using the corresponding functionalized ethyl. The chemical structures of these compounds are determined by NMR ( 1 H, 13 C) and mass spectrometry. The second part concerned the in vitro antifungal activity evaluation of some of the synthesized compounds on Candida albicans . According to the results of evaluation, four compounds (3b, 3c, 3d and 9c) of the substituted 2-thioalkylaryl-benzimidazoles prove to be potent antifungal agent. Introduction of nitro group (NO 2 ) increased significantly the antifungal activity so that their IMQ is ranging between 0.03 and 0.008 μg (or 333 to 1250 times more efficient than the ketoconazole’s). Keywords : synthesis of 2-thioalkylaryl-benzimidazole, antifungal activity, candida albicans.

A series of 3-(3-Arylpropenoyl)imidazopyridine (5a to z) was synthesized by crotonization reaction of 2-methyl-3-acetylimidazopyridine with arylaldehyde derivatives. Structuraldetermination of these new chalcones was done by 1H nuclear magnetic resonance (NMR),13C NMR and electrospray ionization (ESI) mass spectroscopy. All compounds have beenevaluated in vitro for their anthelmintic activities against Haemonchus contortus. Compounds5n, 5s, 5t and 5w showed a great nematicidal activity (LC100) ranging between 0.0005 and0.002 µg/ml. The activity of these four chalcones was equivalent to that of fenbendazole andivermectin which were reference anthelmintic drugs. This study has shown that imidazopyridine-chalcone derivatives are promising candidates for the development of new anthelmintic agents. Key words: Haemonchus contortus, imidazopyridine, chalcone, nematicidal activity.

The title compound, C13H14N2OS2·H2O, appears in the form of bimolecular aggregate in which molecular components are linked by O—H...N hydrogen bonding. The nine-membered imidazo[1,2-a]pyridine system is almost planar, with a mean deviation of 0.026 (1) Å. An intramolecular C—H...O hydrogen bond forms within the imidazo[1,2-a]pyridine system. The crystal packing is consolidated by O—H...O and C—H...O hydrogen bonds, forming a supramolecular structure consisting of perpendicular infinite molecular chains running along the a and c axes.